UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C.WASHINGTON, DC 20549

 

Form 

FORM 10-Q

 

(Mark One)

QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934

For the quarterly period ended March 31, 20202021

OR

TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934

For the transition period from to

Commission file number: 001-37695File Number: 001-38549

 

Proteostasis Therapeutics, Inc.

YUMANITY THERAPEUTICS, INC.

(Exact nameName of registrantRegistrant as specifiedSpecified in its charter)Charter)

 

 

Delaware

20-8436652

(State or Otherother jurisdiction of

Incorporationincorporation or organization)

(I.R.S. Employer


Identification No.)

8040 Guest Street, Suite 5004410

Boston, MassachusettsMA

02135

(Address of Principal Executive Offices)

principal executive offices)

(Zip Code)

(617) 225-0096

(Registrant’s telephone number, including area code)code: 617-409-5300

 

Securities registered pursuant to Section 12(b) of the Act:

Title of each class

Trading Symbol

Symbol(s)

Name of each exchange

on which registered

Common stock,Stock, par value $0.001 per share

PTI

YMTX

The Nasdaq StockCapital Market LLC

Securities registered pursuant to the Section 12(g) of the Act: None

Indicate by check mark whether the registrant (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934 during the preceding 12 months (or for such shorter period that the registrant was required to file such reports), and (2) has been subject to such filing requirements for the past 90 days.    Yes      No  

Indicate by check mark whether the registrant has submitted electronically every Interactive Data File required to be submitted pursuant to Rule 405 of Regulation S-T (§232.405 of this chapter) during the preceding 12 months (or for such shorter period that the registrant was required to submit such files).    Yes      No  

Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, smaller reporting company, or an emerging growth company. See the definitions of “large accelerated filer,” “accelerated filer,” “smaller reporting company”company,” and “emerging growth company” in Rule 12b-2 of the Exchange Act.

 

Large accelerated filer

Accelerated filer

Non-accelerated filer

Smaller reporting company

Emerging growth company

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act.    

Indicate by check mark whether the registrant is a shell company (as defined in Rule 12b-2 of the Exchange Act).    Yes      No  

As of May 11, 2020, there were 52,147,6567, 2021, the registrant had 10,202,506 shares of the registrant’s common stock, $0.001 par value per share, outstanding.

 

 


 


Summary of the Material Risks Associated with Our Business

We are subject to various risks associated with our businesses and industries. These risks include the following:

we have incurred significant operating losses since our inception and anticipate we will incur continued losses for the foreseeable future;

we will need additional funding to advance YTX-7739 through clinical development, which funding may not be available on acceptable terms, or at all. Failure to obtain this necessary capital when needed may force us to delay, limit, or terminate our product development efforts or other operations;

we have concentrated our research and development efforts on the treatment of neurodegenerative diseases, a field that has seen limited success in drug development. Further, our product candidates are based on new approaches and novel technology, which makes it difficult to predict the time and cost of product candidate development and subsequently obtaining regulatory approval;

we depend on our collaboration with Merck and may in the future depend on other collaborations with third parties for the research, development and commercialization of certain of the product candidates we may develop. If any such collaborations are not successful, we may not be able to realize the market potential of those product candidates;

we may encounter difficulties in enrolling subjects in our clinical trials, thereby delaying or preventing development of our product candidates;

our clinical trials may fail to demonstrate adequate safety and efficacy of our product candidates, which would prevent, delay, or limit the scope of regulatory approval and commercialization;

our product candidates may cause serious adverse events or other undesirable side effects that could delay or prevent their regulatory approval, limit the commercial profile of an approved label, or result in significant negative consequences following marketing approval, if any;

we face significant competition in an environment of rapid technological and scientific change, and there is a possibility that our competitors may achieve regulatory approval before we do or develop therapies that are safer, more advanced, or more effective, which may negatively impact our ability to successfully market or commercialize any product candidates we may develop and ultimately harm our financial condition;

the current pandemic of COVID-19 and the future outbreak of other highly infectious or contagious diseases could seriously harm our research, development and potential future commercialization efforts, increase our costs and expenses and have a material adverse effect on our business, financial condition and results of operations;

the regulatory approval processes of the FDA and comparable foreign regulatory authorities are lengthy, time-consuming, and inherently unpredictable. If we are ultimately unable to obtain regulatory approval for our product candidates, we will be unable to generate product revenue and our business will be substantially harmed; and

we may not seek to protect our intellectual property rights in all jurisdictions throughout the world and we may not be able to adequately enforce our intellectual property rights even in the jurisdictions where we seek protection.

The summary risk factors described above should be read together with the text of the full risk factors below, in the section entitled “Risk Factors” in Part II, Item 1A. and the other information set forth in this Quarterly Report on Form 10-Q, including our condensed consolidated financial statements and the related notes, as well as in other documents that we file with the U.S. Securities and Exchange Commission (“SEC”). The risks summarized above or described in full below are not the only risks that we face. Additional risks and uncertainties not precisely known to us, or that we currently deem to be immaterial may also materially adversely affect our business, financial condition, results of operations and future growth prospects.

i


CAUTIONARY NOTE REGARDING FORWARD-LOOKING STATEMENTS

This Quarterly Report on Form 10-Q or this report, including the sections entitled “Risk Factors” and “Management’s Discussion and Analysis of Financial Condition and Results of Operations,” contains forward-looking statements that involve risks and uncertainties, as well as assumptions that, if they never materialize or prove incorrect, could cause our results to differ materially from those expressed or implied by such forward-looking statements. Statements that are not purely historical are forward-looking statements within the meaning of Section 27A of the U.S. Private Securities Litigation Reform Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. Theseamended, that involve substantial risks and uncertainties. All statements, other than statements of historical fact, contained in this Quarterly Report on Form 10-Q, including statements regarding our strategy, future operations, future financial position, future revenue, projected costs, prospects, plans and objectives of management, are forward-looking statements are often identified by thestatements. The words “aim,” “anticipate,” “believes,“believe,“can,“contemplate,” “continue,” “could,” “estimates,“estimate,“expects,“expect,“intends,“intend,” “may,” “plans,“might,” “plan,” “potential,” “predicts,“predict,” “project,” “seek,” “should,” “target,” “will,” “would”“would,” or the negative of these termswords or other comparable terminologysimilar expressions are intended to identify forward-looking statements. Thesestatements, although not all forward-looking statements contain these identifying words.

The forward-looking statements in this Quarterly Report on Form 10-Qinclude, but are not limited to,among other things, statements about:

 

our planned Phase 3 clinical trials with our combination therapy candidates, nesolicaftor (PTI-428), posenacaftor (PTI-801), and dirocaftor (PTI-808), including timing of the progress and the potential filing of a Marketing Authorization Application, or MAA;

the developmenttiming, progress and results of preclinical studies and clinical trials for our programs and product candidates, including statements regarding the timing of initiation and completion and the outcome of clinical studies or trials and related preparatory work, the period during which the results of the trials will become available and our research and development programs;

our ability to recruit and enroll suitable patients in our clinical trials;

the potential attributes and benefits of our product candidates;

our ability to develop and advance product candidates into, and successfully complete, clinical studies;

the timing, scope or likelihood of regulatory filings and approvals;

 

our ability to advance our product candidates into, and successfully complete, clinical trials;

our ability to establish additional collaborations for our product candidates;

our estimates regarding anticipated filing of investigational new drugs, or INDs and/or amended protocols for our product candidates;

our ability to obtain and maintain regulatory approval of our combination solutions, for any indication, and any related restrictions, limitations or warnings of an approved drug or therapy;

our ability to obtain and maintain sanctioningregulatory approval for our product candidates, and any related restrictions, limitations or favorable scoringwarnings in the label of an approved product candidate;

the implementation of our business model and our strategic plans for our business, product candidates, technology and our discovery engine;

our commercialization, marketing and manufacturing capabilities and strategy;

the pricing and reimbursement of our product candidates, if approved;

the rate and degree of market acceptance of our product candidates, if approved;

our ability to establish or maintain collaborations or strategic relationships or obtain additional funding;

our ability to contract with and rely on third parties to assist in conducting our clinical trials or protocols from other third parties, such as the Therapeutics Development Network, or TDN, of the Cystic Fibrosis Foundation, or CFF, or the Clinical Trial Network, or CTN, of the European Cystic Fibrosis Society;

intense competition in the cystic fibrosis market and the ability of our competitors, many of whom have greater resources than we do, to run clinical trials that may limit the patients available for our trials, and to offer different, better or lower cost therapeutic alternatives thanmanufacturing our product candidates;

anticipated regulatory developmentsthe size and growth potential of the markets for our product candidates, and our ability to serve those markets, either alone or in partnership with others;

our ability to obtain funding for our operations, including funding necessary to complete further development, approval and, if approved, commercialization of our product candidates;

the period over which we anticipate our existing cash and cash equivalents will be sufficient to fund our operating expenses and capital expenditure requirements;

the potential for our business development efforts to maximize the potential value of our portfolio;

our ability to compete with other companies currently marketing or engaged in the United States and foreign countries;development of treatments for the indications that we are pursuing for our product candidates;

 

our plans to research, develop, manufacture and commercialize our combination solutions, including expected preclinical and clinical results and timing;

our expectations regarding our ability to obtain and maintain intellectual property protection for our proprietary assets;product candidates;

the size and growth of the potential markets for our combination solutions, and our ability to serve those markets;financial performance;

the rate and degree of commercial scope and potential, as well as market acceptance of our combination solutions for any indication;

 

the benefits of U.S. Food and Drug Administration, or FDA, and European Commission designations such as, including, without limitation, Fast Track, Orphan Drug and Breakthrough Therapy;

our commercialization, marketing, and manufacturing capabilities and strategy;

our ability to obtainretain the continued service of our key professionals and to identify, hire and retain additional qualified professionals;

our expectations related to the use of our cash reserves;

our estimates regarding expenses, future revenue, capital requirements and needs for additional financing;

the impact of laws and regulations, including without limitation recently enacted tax reform legislation;

 

our estimates regarding expenses, future revenues and anticipated capital requirements;

our ability to attract and retain qualified key scientific or management personnel;

our expectations regarding the impact time during which we are an emerging growth company under the JOBS Act;

ii


the effect of COVID-19 onthe ongoing coronavirus disease 2019,foregoing; and

other risks and uncertainties, including those listed under the caption “Risk Factors” in Part II, Item 1A.

We may not actually achieve the plans, intentions or COVID-19, pandemic, including the expected duration of disruptionexpectations disclosed in our forward-looking statements, and immediate and long-term impact and effectyou should not place undue reliance on our businessforward-looking statements. Actual results or events could differ materially from the plans, intentions and operations; and

other forward-looking statements discussed elsewhere in this report.

2


expectations disclosed in the forward-looking statements we make. We have included important factors in the cautionary statements included in this Quarterly Report on Form You should refer to10-Q, particularly in the “Risk Factors” for a discussion of important factorssection, that maywe believe could cause our actual results or events to differ materially from those expressed or implied by our forward-looking statements. As a result of these factors, we cannot assure you that the forward-looking statements that we make. Moreover, we operate in a competitive and rapidly changing environment. New risk factors and uncertainties may emerge from time to time, and it is not possible for management to predict all risk factors and uncertainties. Our forward-looking statements do not reflect the potential impact of any future acquisitions, mergers, dispositions, collaborations, joint ventures, or investments we may make or enter into.

You should read this Quarterly Report and the documents that we file with the Securities and Exchange Commission with the understanding that our actual future results may be materially different from what we expect. The forward-looking statements contained in this report will prove to be accurate. Furthermore, if our forward-looking statements prove to be inaccurate, the inaccuracy may be material. In lightQuarterly Report on Form 10-Q are made as of the significant uncertainties in these forward-looking statements, you shoulddate of this Quarterly Report on Form 10-Q, and we do not regard these statements as a representation or warranty by us orassume any other person that we will achieve our objectives and plans in any specified time frame, or at all. We undertake no obligation to publicly update any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by applicable law. You should, therefore, not rely on these forward-looking statements as representing our views as of any date subsequent to the date of this report.

Any forward-looking statements in this report reflect our current views with respect to future events and with respect to our future financial performance and involve known and unknown risks, uncertainties and other factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by these forward-looking statements. Factors that may cause actual results to differ materially from current expectations include, among other things, those described under Part II, Item 1A. Risk Factors and elsewhere in this report. Given these uncertainties, you should not place undue reliance on these forward-looking statements. Except as required by law, we assume no obligation to update or revise these forward-looking statements for any reason, even if new information becomes available in the future.

This report contains estimates, projections and other information concerning our industry, the general business environment, and the markets for certain diseases, including estimates regarding the potential size of those markets and the estimated incidence and prevalence of certain medical conditions. Information that is based on estimates, forecasts, projections, market research or similar methodologies is inherently subject to uncertainties and actual events, circumstances or numbers, including actual disease prevalence rates and market size, may differ materially from the information reflected in this report. Unless otherwise expressly stated, we obtained this industry, business information, market data, prevalence information and other data from reports, research surveys, studies and similar data prepared by market research firms and other third parties, industry, medical and general publications, government data, and similar sources, in some cases applying our own assumptions and analysis that may, in the future, not prove to have been accurate.

Symdeko/Symkevi and Trikafta are trademarks of Vertex Pharmaceuticals Incorporated.

3


Proteostasis Therapeutics, Inc.

INDEX

 

iii


Table of Contents

Page

PART I – I.

FINANCIAL INFORMATION

1

Item 1.

Condensed Financial Statements (unaudited):(Unaudited)

1

Condensed Consolidated Balance Sheets as of March 31, 2020 and December 31, 2019

5

1

Condensed Consolidated Statements of Operations and Comprehensive Loss for the Three Months Ended March 31, 2020 and 2019

6

2

Condensed Consolidated Statements of Stockholders’ Equity for the Three Months Ended March 31, 2020 and 2019Comprehensive Income (Loss)

7

3

Condensed Consolidated Statements of Cash Flows for the Three Months Ended March 31, 2020 and 2019

8

5

Notes to Unaudited Condensed Consolidated Financial Statements

9

6

Item 2.

Management’s Discussion and Analysis of Financial Condition and Results of Operations

18

20

Item 3.

Quantitative and Qualitative Disclosures About Market Risk

28

30

Item 4.

Management’s Evaluation of our Disclosure Controls and Procedures

28

31

PART II.

PART II – OTHER INFORMATION

32

Item 1.

Legal Proceedings

29

32

Item 1A.

Risk Factors

29

32

Item 2.

Unregistered Sales of Equity Securities and Use of Proceeds

69

Item 3.

70Defaults Upon Senior Securities

69

Item 4.

Mine Safety Disclosures

69

Item 5.

Other Information

70

69

Item 6.

Exhibits

71

70

Signatures

72

71

 

4iv


PART I — FINANCIALI—FINANCIAL INFORMATION

PROTEOSTASISItem 1. Financial Statements.

YUMANITY THERAPEUTICS, INC.

CONDENSED CONSOLIDATED BALANCE SHEETS

(In thousands, except share and per share amounts)

(Unaudited)

 

 

March 31,

 

 

December 31,

 

 

 

2020

 

 

2019

 

Assets

 

 

 

 

 

 

 

 

Current assets:

 

 

 

 

 

 

 

 

Cash and cash equivalents

 

$

33,351

 

 

$

25,008

 

Short-term investments

 

 

23,753

 

 

 

44,459

 

Prepaids and other current assets

 

 

2,489

 

 

 

1,404

 

Total current assets

 

 

59,593

 

 

 

70,871

 

Operating lease, right-of-use asset

 

 

12,318

 

 

 

12,631

 

Property and equipment, net

 

 

350

 

 

 

394

 

Restricted cash

 

 

828

 

 

 

828

 

Total assets

 

$

73,089

 

 

$

84,724

 

Liabilities and Stockholders’ Equity

 

 

 

 

 

 

 

 

Current liabilities:

 

 

 

 

 

 

 

 

Accounts payable

 

$

1,201

 

 

$

2,283

 

Accrued expenses

 

 

4,725

 

 

 

6,864

 

Operating lease liabilities

 

 

1,179

 

 

 

1,153

 

Short-term borrowings

 

 

1,099

 

 

 

 

Total current liabilities

 

 

8,204

 

 

 

10,300

 

Derivative liability

 

 

3

 

 

 

3

 

Operating lease liabilities, net of current portion

 

 

11,742

 

 

 

12,043

 

Total liabilities

 

 

19,949

 

 

 

22,346

 

Commitments and contingencies

 

 

 

 

 

 

 

 

Stockholders’ equity:

 

 

 

 

 

 

 

 

Preferred stock, $0.001 par value; 5,000,000 shares authorized; no shares

   issued and outstanding as of March 31, 2020 and December 31, 2019

 

 

 

 

 

 

Common stock, $0.001 par value; 125,000,000 shares authorized;

   52,147,656 and 52,116,629 shares issued and outstanding as of

   March 31, 2020 and December 31, 2019, respectively

 

 

52

 

 

 

52

 

Additional paid-in capital

 

 

399,583

 

 

 

398,979

 

Accumulated other comprehensive income

 

 

43

 

 

 

7

 

Accumulated deficit

 

 

(346,538

)

 

 

(336,660

)

Total stockholders’ equity

 

 

53,140

 

 

 

62,378

 

Total liabilities and stockholders’ equity

 

$

73,089

 

 

$

84,724

 

The accompanying unaudited notes are an integral part of these condensed financial statements.

5


PROTEOSTASIS THERAPEUTICS, INC.

CONDENSED STATEMENTS OF OPERATIONS AND COMPREHENSIVE LOSS

(In thousands, except share and per share amounts)

(Unaudited)

 

 

Three Months Ended March 31,

 

 

 

2020

 

 

2019

 

Revenue

 

$

 

 

$

5,000

 

Operating expenses:

 

 

 

 

 

 

 

 

Research and development

 

 

6,518

 

 

 

16,148

 

General and administrative

 

 

3,587

 

 

 

3,943

 

Total operating expenses

 

 

10,105

 

 

 

20,091

 

Loss from operations

 

 

(10,105

)

 

 

(15,091

)

Interest income

 

 

207

 

 

 

357

 

Interest expense

 

 

(3

)

 

 

 

Other income, net

 

 

23

 

 

 

316

 

Net loss

 

$

(9,878

)

 

$

(14,418

)

Net loss per share—basic and diluted

 

$

(0.19

)

 

$

(0.28

)

Weighted average common shares outstanding—basic and

   diluted

 

 

52,146,633

 

 

 

50,976,907

 

Other comprehensive income:

 

 

 

 

 

 

 

 

Unrealized gain on investments

 

 

36

 

 

 

17

 

Comprehensive loss

 

$

(9,842

)

 

$

(14,401

)

The accompanying unaudited notes are an integral part of these condensed financial statements.

6


PROTEOSTASIS THERAPEUTICS, INC.

CONDENSED STATEMENTS OF STOCKHOLDERS’ EQUITY

(In thousands, except share amounts)

(Unaudited)

 

 

 

Common Stock

 

 

Additional

Paid-

 

 

Accumulated

Other

Comprehensive

 

 

Accumulated

 

 

Total

Stockholders’

 

 

 

Shares

 

 

Amount

 

 

in Capital

 

 

Income

 

 

Deficit

 

 

Equity

 

Balances at December 31, 2019

 

 

52,116,629

 

 

$

52

 

 

$

398,979

 

 

$

7

 

 

$

(336,660

)

 

$

62,378

 

Stock-based compensation expense

 

 

 

 

 

 

 

 

578

 

 

 

 

 

 

 

 

 

578

 

Issuance of common stock pursuant

   to employee stock purchase plan

 

 

31,027

 

 

 

 

 

 

26

 

 

 

 

 

 

 

 

 

26

 

Other comprehensive income

 

 

 

 

 

 

 

 

 

 

 

36

 

 

 

 

 

 

36

 

Net loss

 

 

 

 

 

 

 

 

 

 

 

 

 

 

(9,878

)

 

 

(9,878

)

Balances at March 31, 2020

 

 

52,147,656

 

 

$

52

 

 

$

399,583

 

 

$

43

 

 

$

(346,538

)

 

$

53,140

 

 

 

Common Stock

 

 

Additional

Paid-

 

 

Accumulated

Other

Comprehensive

 

 

Accumulated

 

 

Total

Stockholders’

 

 

 

Shares

 

 

Amount

 

 

in Capital

 

 

Income

 

 

Deficit

 

 

Equity

 

Balances at December 31, 2018

 

 

50,808,422

 

 

$

51

 

 

$

391,825

 

 

$

1

 

 

$

(277,535

)

 

$

114,342

 

Exercise of stock options

 

 

2,543

 

 

 

 

 

 

3

 

 

 

 

 

 

 

 

 

3

 

Stock-based compensation expense

 

 

 

 

 

 

 

 

801

 

 

 

 

 

 

 

 

 

801

 

Issuance of common stock for payment of

   consulting services

 

 

46,153

 

 

 

 

 

 

169

 

 

 

 

 

 

 

 

 

169

 

Issuance of common stock pursuant

   to employee stock purchase plan

 

 

22,615

 

 

 

 

 

 

53

 

 

 

 

 

 

 

 

 

53

 

Vesting of restricted stock units

 

 

163,425

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Other comprehensive income

 

 

 

 

 

 

 

 

 

 

 

17

 

 

 

 

 

 

17

 

Net loss

 

 

 

 

 

 

 

 

 

 

 

 

 

 

(14,418

)

 

 

(14,418

)

Balances at March 31, 2019

 

 

51,043,158

 

 

$

51

 

 

$

392,851

 

 

$

18

 

 

$

(291,953

)

 

$

100,967

 

   March 31,  December 31, 
   2021  2020 

Assets

   

Current assets:

   

Cash and cash equivalents

  $52,114  $80,819 

Marketable securities

   10,771   4,498 

Prepaid expenses and other current assets

   3,752   2,264 
  

 

 

  

 

 

 

Total current assets

   66,637   87,581 

Property and equipment, net

   685   874 

Operating lease right-of-use assets

   22,431   23,678 

Deposits

   386   386 

Restricted cash

   2,066   2,066 

Assets held-for-sale

   83   250 
  

 

 

  

 

 

 

Total assets

  $92,288  $114,835 
  

 

 

  

 

 

 

Liabilities and Stockholders’ Equity

   

Current liabilities:

   

Accounts payable

  $1,947  $7,384 

Accrued expenses and other current liabilities

   3,549   7,851 

Current portion of long-term debt

   3,675   2,891 

Operating lease liabilities

   4,611   4,468 

Current portion of finance lease obligation

   109   166 

Deferred revenue

   4,572   8,104 
  

 

 

  

 

 

 

Total current liabilities

   18,463   30,864 

Long-term debt, net of discount and current portion

   11,413   13,237 

Operating lease liabilities, net of current portion

   13,283   14,479 

Finance lease obligation, net of current portion

   35   48 

Other liabilities

   162   —   
  

 

 

  

 

 

 

Total liabilities

   43,356   58,628 
  

 

 

  

 

 

 

Commitments and contingencies (Note 10)

   

Stockholders’ equity/(deficit):

   

Preferred stock, $0.001 par value; 5,000,000 shares authorized; no shares issued and outstanding as of March 31, 2021 and December 31, 2020, respectively

   —     —   

Common stock, $0.001 par value; 125,000,000 shares authorized; no shares issued and 10,193,831 shares issued and outstanding as of March 31, 2021 and December 31, 2020, respectively

   10   10 

Additional paid-in capital

   205,414   204,007 

Accumulated deficit

   (156,492  (147,810
  

 

 

  

 

 

 

Total stockholders’ equity/(deficit)

   48,932   56,207 
  

 

 

  

 

 

 

Total liabilities and stockholders’ equity/(deficit)

  $92,288  $114,835 
  

 

 

  

 

 

 

The accompanying unaudited notes are an integral part of these condensed consolidated financial statements.

7


PROTEOSTASISYUMANITY THERAPEUTICS, INC.

CONDENSED CONSOLIDATED STATEMENTS OF CASH FLOWSOPERATIONS

(In thousands)thousands, except share/unit and per share/unit amounts)

(Unaudited)

 

 

 

Three Months Ended March 31,

 

 

 

2020

 

 

2019

 

Cash flows from operating activities:

 

 

 

 

 

 

 

 

Net loss

 

$

(9,878

)

 

$

(14,418

)

Adjustments to reconcile net loss to cash used in operating activities:

 

 

 

 

 

 

 

 

Depreciation and amortization

 

 

357

 

 

 

351

 

Accretion of short-term investments

 

 

(26

)

 

 

(317

)

Stock-based compensation expense

 

 

578

 

 

 

801

 

Stock issued for consulting services

 

 

 

 

 

169

 

Changes in operating assets and liabilities:

 

 

 

 

 

 

 

 

Prepaids and other current assets

 

 

(1,085

)

 

 

(653

)

Other assets

 

 

 

 

 

(88

)

Accounts payable

 

 

(1,082

)

 

 

120

 

Accrued expenses

 

 

(2,139

)

 

 

858

 

Operating lease liabilities

 

 

(275

)

 

 

(252

)

Net cash used in operating activities

 

 

(13,550

)

 

 

(13,429

)

Cash flows from investing activities:

 

 

 

 

 

 

 

 

Purchases of short-term investments

 

 

(5,232

)

 

 

(20,844

)

Proceeds received from maturities of short-term investments

 

 

26,000

 

 

 

37,000

 

Purchases of property and equipment

 

 

 

 

 

(9

)

Net cash provided by investing activities

 

 

20,768

 

 

 

16,147

 

Cash flows from financing activities:

 

 

 

 

 

 

 

 

Proceeds from exercise of stock options

 

 

 

 

 

3

 

Proceeds from issuance of common stock pursuant to employee stock purchase plan

 

 

26

 

 

 

53

 

Proceeds from issuance of short-term borrowings

 

 

1,220

 

 

 

 

Repayment of short-term borrowings

 

 

(121

)

 

 

 

Net cash provided by financing activities

 

 

1,125

 

 

 

56

 

Net increase in cash, cash equivalents and restricted cash

 

 

8,343

 

 

 

2,774

 

Cash, cash equivalents and restricted cash at beginning of period

 

 

25,836

 

 

 

29,638

 

Cash, cash equivalents and restricted cash at end of period

 

$

34,179

 

 

$

32,412

 

   Three Months Ended
March 31,
 
   2021  2020 

Collaboration revenue

  $3,532  $—   

Operating expenses:

   

Research and development

   6,779   5,029 

General and administrative

   6,052   2,032 
  

 

 

  

 

 

 

Total operating expenses

   12,831   7,061 
  

 

 

  

 

 

 

Loss from operations

   (9,299  (7,061
  

 

 

  

 

 

 

Other income (expense):

   

Change in fair value of preferred unit warrant liability

   —     5 

Interest expense

   (488  (454

Interest income and other income (expense), net

   (29  45 

Gain on debt extinguishment

   1,134   —   
  

 

 

  

 

 

 

Total other income (expense), net

   617   (404
  

 

 

  

 

 

 

Net loss

  $(8,682 $(7,465
  

 

 

  

 

 

 

Net loss applicable to common shareholders

   (8,682  (7,465
  

 

 

  

 

 

 

Net loss per share/unit, basic and diluted

  $(0.85 $(3.47
  

 

 

  

 

 

 

Weighted average common shares/units outstanding, basic and diluted

   10,193,328   2,150,017 
  

 

 

  

 

 

 

The accompanying unaudited notes are an integral part of these condensed consolidated financial statements.

YUMANITY THERAPEUTICS, INC.

CONDENSED CONSOLIDATED STATEMENTS OF COMPREHENSIVE LOSS

(In thousands)

(Unaudited)

 

   Three Months
Ended

March 31,
 
   2021  2020 

Net loss

  $(8,682 $(7,465

Other comprehensive income:

   

Unrealized gains on marketable securities, net of tax of $0

   —     —   
  

 

 

  

 

 

 

Comprehensive loss

  $(8,682 $(7,465
  

 

 

  

 

 

 

8The accompanying notes are an integral part of these condensed consolidated financial statements.


PROTEOSTASIS

YUMANITY THERAPEUTICS, INC.

CONDENSED CONSOLIDATED STATEMENTS OF PREFERRED UNITS AND STOCKHOLDERS’ EQUITY (DEFICIT)

(In thousands, except share/unit amounts)

(Unaudited)

   Preferred Units   Common Units   Common Stock   Additional
Paid-in
   Accumulated
Other
Comprehensive
   Accumulated  Total
Stockholders’
Equity
 
   Units   Amount   Units   Amount   Shares   Amount   Capital   Gain (Loss)   Deficit  (Deficit) 

Balances at December 31, 2019

   12,391,101   $89,699    2,163,099   $5,120    —     $ —     $ —     $ —     $(97,020 $(91,900

Stock/equity-based compensation expense

   —      —      —      570    —      —      —      —      —     570 

Net loss

   —      —      —      —      —      —      —      —      (7,465  (7,465
  

 

 

   

 

 

   

 

 

   

 

 

   

 

 

   

 

 

   

 

 

   

 

 

   

 

 

  

 

 

 

Balances at March 31, 2020

   12,391,101    89,699    2,163,099   $5,690    —     $—     $—     $—     $(104,485 $(98,795
  

 

 

   

 

 

   

 

 

   

 

 

   

 

 

   

 

 

   

 

 

   

 

 

   

 

 

  

 

 

 

   Preferred Units   Common Units   Common Stock   Additional
Paid-in
   Accumulated
Other
Comprehensive
   Accumulated  Total
Stockholders’
Equity
 
   Units   Amount   Units   Amount   Shares   Amount   Capital   Gain (Loss)   Deficit  (Deficit) 

Balances at December 31, 2020

   —     $ —      —     $ —      10,193,831   $10   $204,007   $ —     $(147,810 $56,207 

Stock/equity-based compensation expense

   —      —      —      —      —      —      1,407    —      —     1,407 

Net loss

   —      —      —      —      —        —      —      (8,682  (8,682
  

 

 

   

 

 

   

 

 

   

 

 

   

 

 

   

 

 

   

 

 

   

 

 

   

 

 

  

 

 

 

Balances at March 31, 2021

   —      —      —     $—      10,193,831   $10   $205,414   $—     $(156,492 $48,932 
  

 

 

   

 

 

   

 

 

   

 

 

   

 

 

   

 

 

   

 

 

   

 

 

   

 

 

  

 

 

 

The accompanying notes are an integral part of these condensed consolidated financial statements.

YUMANITY THERAPEUTICS, INC.

CONDENSED CONSOLIDATED STATEMENTS OF CASH FLOWS

(In thousands)

(Unaudited)

   Three Months Ended
March 31,
 
   2021  2020 

Cash flows from operating activities:

   

Net loss

  $(8,682 $(7,465

Adjustments to reconcile net loss to net cash used in operating activities:

   

Net amortization of premiums (accretion of discounts) on marketable securities

   (4  (3

Depreciation and amortization expense

   200   200 

Non-cash lease expense

   1,247   179 

Stock/equity-based compensation expense

   1,407   570 

Other non-cash expense

   48   —   

Non-cash interest expense

   155   116 

Gain on debt extinguishment

   (1,134  —   

Change in fair value of preferred unit warrant liability

   —     (5

Gain on sale of property and equipment

   (2  —   

Changes in operating assets and liabilities:

   

Prepaid expenses and other current assets

   (1,374  105 

Deposits

   —     (848

Operating lease liabilities

   (1,053  (291

Accounts payable

   (5,437  (651

Accrued expenses and other current liabilities

   (4,127  (190

Deferred revenue

   (3,532  —   
  

 

 

  

 

 

 

Net cash used in operating activities

   (22,288  (8,283
  

 

 

  

 

 

 

Cash flows from investing activities:

   

Purchases of marketable securities

   (9,869  —   

Proceeds from sales and maturities of marketable securities

   3,600   1,350 

Purchases of property and equipment

   (6  (170
  

 

 

  

 

 

 

Net cash (used in) provided by investing activities

   (6,275  1,180 
  

 

 

  

 

 

 

Cash flows from financing activities:

   

Payments of debt issuance costs related to long-term debt

   (72  —   

Payments of finance lease obligations

   (70  (88
  

 

 

  

 

 

 

Net cash used in financing activities

   (142  (88
  

 

 

  

 

 

 

Net decrease in cash, cash equivalents and restricted cash

   (28,705  (7,191

Cash, cash equivalents and restricted cash at beginning of period

   82,885   14,246 
  

 

 

  

 

 

 

Cash, cash equivalents and restricted cash at end of period

  $54,180  $7,055 
  

 

 

  

 

 

 

Supplemental cash flow information:

   

Cash paid for interest

  $328  $263 

The accompanying notes are an integral part of these condensed consolidated financial statements.

YUMANITY THERAPEUTICS, INC.

NOTES TO CONDENSED CONSOLIDATED FINANCIAL STATEMENTS

(Unaudited)

1. Nature of Business and Basis of Presentation

1.

Nature of the Business

Yumanity Therapeutics, Inc. (formerly Proteostasis Therapeutics, Inc. (the, and together with its wholly owned subsidiaries, the “Company” or “Yumanity”) was incorporated in Delaware on December 13, 2006. The Company is a clinical stage biopharmaceutical company committed toengaged in the discoveryresearch and development of novel therapeutics to treat cystic fibrosis (“CF”) through theratyping, or the process of matching modulators to individual response to treatment regardless of CFTR mutations. CF is a diseasetreatments for neurodegenerative diseases caused by defectsprotein misfolding.

The Company is subject to risks similar to those of other early clinical stage companies in the function or abundancebiopharmaceutical industry, including dependence on key individuals, the need to develop commercially viable products, competition from other companies, many of cystic fibrosis transmembrane conductance regulator (“CFTR”) protein. Although, CF is defined as a monogenic recessive genetic disorder caused by mutations inwhom are larger and better capitalized, the CFTR gene, there is a broad rangeimpact of disease activity for different organ systems in CF, including lung disease, meconium ileus, diabetes,the COVID-19 pandemic and liver disease, even for CF patients who are homozygous for the most common mutation, F508del mutation. In summary, CF genotype does not always match CF phenotype.

Since its inception,need to obtain adequate additional financing to fund the Company has devoted substantially alldevelopment of its efforts to organizing and staffingproduct candidates. There can be no assurance that the Company, business planning, raising capital, acquiring and developing product and technology rights, and conductingCompany’s research and development activities. It has funded its operations to date with proceedswill be successfully completed, that adequate protection for the Company’s intellectual property will be maintained, that any product candidates developed will obtain required regulatory approval or that any approved products will be commercially viable. Even if the Company’s development efforts are successful, it is uncertain when, if ever, the Company will generate significant revenue from the sale of preferred stock,its products.

Merger with Proteostasis Therapeutics, Inc.

On December 22, 2020, Proteostasis Therapeutics, Inc. (“Proteostasis” or “PTI”) completed its previously announced merger transaction with Yumanity, Inc. (formerly Yumanity Therapeutics, Inc.) in accordance with the issuanceterms of convertible promissory notes, proceeds from its initial public offering in February 2016, proceeds from its follow-on public offerings,the Agreement and payments receivedPlan of Merger and Reorganization, dated as of August 22, 2020, as amended on November 6, 2020 (the “Merger Agreement”), by and among Pangolin Merger Sub, Inc., a wholly-owned subsidiary of Proteostasis (“Merger Sub”), Yumanity Holdings, LLC (“Holdings”) and Yumanity, Inc., pursuant to which Merger Sub merged with and into Yumanity, Inc., with Yumanity, Inc. surviving as a wholly owned subsidiary of Proteostasis (the “Merger”). Immediately prior to the effective time of the Merger, Holdings merged with and into Yumanity, Inc. and Yumanity, Inc. continued to exist as the surviving corporation. On December 22, 2020, in connection with, collaboration agreements and prior to the completion of, the Merger, Proteostasis effected a research grant,1-for-20 reverse stock split of its common stock (the “Reverse Stock Split”). Immediately following the Merger, Proteostasis changed its name to “Yumanity Therapeutics, Inc.”

At the effective time of the Merger (the “Effective Time”), each share of Yumanity Inc.’s common stock, par value $0.01 (the “Yumanity Common Stock”), outstanding immediately prior to the Effective Time was converted into the right to receive shares of PTI based on an exchange ratio set forth in the Merger Agreement. At the Effective Time following the Reverse Stock Split, the exchange ratio was determined to be 0.2108 shares of PTI Common Stock for each share of Yumanity Common Stock (the “Exchange Ratio”). At the closing of the Merger on December 22, 2020, PTI issued an aggregate of 6,024,433 shares of its common stock to Yumanity, based on the Exchange Ratio. In addition, all options and warrants exercisable for shares of common stock of Yumanity, Inc. became options and warrants exercisable for shares of common stock of PTI equal to the Exchange Ratio multiplied by the number of shares of Yumanity Inc.’s common stock previously represented by such stock options and warrants, as wellapplicable, with a proportionate adjustment in exercise price. No fractional shares were issued in connection with the Exchange Ratio.

The transaction was accounted for as funds froma reverse merger and as an asset acquisition in accordance with GAAP. Under this method of accounting, Yumanity was deemed to be the saleaccounting acquirer for financial reporting purposes. This determination was primarily based on the fact that, immediately following the Merger: (i) Yumanity’s equity holders owned a majority of the voting rights in the combined organization, (ii) Yumanity designated a majority of the members (7 of 9) of the initial board of directors of the combined organization and (iii) Yumanity’s senior management hold all key positions in the senior management of the combined organization. Accordingly, for accounting purposes, (i) the Merger was treated as the equivalent of the Yumanity issuing stock underto acquire the at-the-market offering program described below. The Company does not have any products approvednet assets of PTI, (ii) the net assets of PTI were allocated a portion of the transaction price and recorded based upon their relative fair values in the financial statements at the time of closing, (iii) the reported historical operating results of the combined organization prior to the Merger will be those of Yumanity and (iv) for sale and has not generated any revenue from product sales.

The Company has not generated any revenue since inception.periods prior to the transaction, shareholders’ equity of the combined organization is presented based on the historical equity structure of Yumanity. As a result, as of the closing date of the Merger, the net assets of PTI were recorded at their acquisition-date fair values in the financial statements of Yumanity and the reported operating results prior to the Merger will be those of Yumanity. As used herein, the words “the Company” refer to, for periods following the Merger, Yumanity Therapeutics, Inc., together with its wholly owned subsidiaries, and for periods prior to the Merger, Holdings, and its wholly owned subsidiary, as applicable.

The Yumanity Reorganization

On December 22, 2020, immediately prior to the closing of the Merger, pursuant to the terms of the Merger Agreement, the Company has incurred recurring lossescompleted the Yumanity Reorganization whereby Holdings, the sole stockholder and requires significant cash resourcesholding company parent of Yumanity, Inc., merged with and into Yumanity, Inc., with Yumanity, Inc. as the surviving corporation. In connection with the Yumanity Reorganization, each outstanding common unit of Holdings was exchanged for shares of common stock of Yumanity, Inc. based upon a ratio associated with the terms of each common unit, each outstanding preferred unit of Holdings was converted into shares of common stock of Yumanity, Inc. based upon the ratio associated with each individual series of preferred units, each outstanding option to executepurchase shares of common units of Holdings was converted into an outstanding option to purchase shares of common stock of Yumanity, Inc. on a 1-for-1 basis, with a corresponding adjustment to the exercise price, and each outstanding warrant to purchase preferred units or common units of Holdings was converted into a warrant to purchase shares of common stock of Yumanity, Inc. based upon the ratio associated with each individual series of preferred units or on a 1-for-1 basis, respectively, with a corresponding adjustment to the exercise price, as applicable.

Basis of presentation

The Company’s condensed consolidated financial statements have been prepared in conformity with accounting principles generally accepted in the United States of America (“GAAP”). Any reference in these notes to applicable guidance is meant to refer to the authoritative GAAP as found in the Accounting Standards Codification (“ASC”) and Accounting Standards Update (“ASU”) of the Financial Accounting Standards Board (“FASB”). The accompanying condensed consolidated financial statements include the accounts of the Company and its business plans. In accordance with ASC 205-40, wholly owned subsidiaries. All intercompany accounts and transactions have been eliminated in consolidation. Unless otherwise noted, all references to common stock/unit share and per share amounts have also been adjusted to reflect the Exchange Ratio.

Going Concern (“ASC 205-40”), theconcern

The Company has evaluated whether there are certain conditions and events, considered in the aggregate, that raise substantial doubt about the Company’s ability to continue as a going concern within one year after the original issuance date of the condensed consolidated financial statements are issued. As of March 31, 2020,statements.

Since its inception, the Company had an accumulated deficit of $346.5 million.has funded its operations primarily with equity and debt including proceeds from the Merger. The Company has incurred recurring losses and negative cash flows from operations since its inception. Duringinception, including net losses of $8.7 million for the three monthsthree-month period ended March 31, 2020,2021. In addition, as of March 31, 2021, the Company incurred losseshad an accumulated deficit of $9.9 million and used $13.6 million of cash in operations. $156.5 million. The Company expects that itsto continue to generate operating losses and negative cash flows will continue for the foreseeable future. TheAs of March 31, 2021, the Company currently expects that its cash, cash equivalents and short-term investments of $57.1 millionmarketable securities will be sufficient to fund its operating expenses, capital expenditure requirements and capital requirements, based upon its current operating plan, for at least 12 months fromdebt service payments into the date that these financial statements are issued. However, additional funding will be necessary to fund its proposed Phase 3 Modulator Options to RestorE CFTR (“MORE”) trial and to advance the Company’s proprietary combination therapy candidates through regulatory approval and into commercialization, if approved. third quarter of 2022.

The Company will seekrequire additional financing to fund operations and plans to obtain additional funding through private or public equity financings, debt financings, collaboration agreements,or other capital sources, including collaborations with other companies or other strategic alliances and licensing arrangements. Although the Company has been successful in raising capital in the past, theretransactions. There is no assurance that itthe Company will be successful in obtaining such additional financingsufficient funding on terms acceptable to the Company to fund continuing operations, if at all, and the Company may not be able to enter into collaborations or other arrangements. The novel coronavirus (“COVID-19”) pandemic continues to rapidly evolve and has already resulted in a significant disruption of global financial markets. If the disruption persists and deepens, the Company could experience an inability to access additional capital, when and if needed.all. If the Company is unable to obtain additional funding, the Company couldwill be forced to delay, reduce or eliminate some or all of its research and development programs, product portfolio expansion or commercialization efforts, which could adversely affect its business prospects, or the Company may be unable to continue operations.

At-the-Market Offering ProgramImpact of the COVID-19

In MayThe COVID-19 pandemic, which began in December 2019 and has spread worldwide, has caused many governments to implement measures to slow the spread of the outbreak. The outbreak and government measures taken in response have had a significant impact, both direct and indirect, on businesses and commerce, as worker shortages have occurred, supply chains have been disrupted, and facilities and production have been suspended. The future progression of the pandemic and its effects on the Company’s business and operations are uncertain. The COVID-19 pandemic may affect the Company’s ability to initiate and complete preclinical studies, delay its clinical trial or future clinical trials, disrupt regulatory activities, or have other adverse effects on its business and operations. The pandemic has already caused significant disruptions in the financial markets, and may continue to cause such disruptions, which could impact the Company’s ability to raise additional funds to support its operations. Moreover, the pandemic has significantly impacted economies worldwide and could result in adverse effects on the Company’s business and operations.

The Company is monitoring the potential impact of the COVID-19 pandemic on its business and financial statements. To date, the Company entered into a sales agreement with H.C. Wainwright & Co., LLC (“HCW”) with respect to an at-the-market (“ATM”) offering program under whichhas not experienced material business disruptions or incurred impairment losses in the Company may issue and sell, from time-to-time at its sole discretion, sharescarrying values of its common stock, in an aggregate offering amount of up to $56.6 million (the “HCW ATM program”). HCW acts as the Company’s sales agent and will use commercially reasonable efforts to sell shares of common stock from time-to-time, based upon instruction from the Company. Common stock will be sold at prevailing market prices at the time of the sale, andassets as a result prices may vary. The Company will pay HCW up to 3% of the gross proceeds frompandemic and it is not aware of any common stock sold through the sales agreement. As of December 31, 2019, the Company sold 987,653 shares ofspecific related event or circumstance that would require it to revise its common stock for total net proceeds of approximately $3.5 million under the HCW ATM program.estimates

reflected in these condensed consolidated financial statements. The Company did not sell any shares of its common stock under the ATM program during the three months ended March 31, 2020.

In March 2018, the Company entered into a sales agreement with Leerink Partners LLC (“Leerink”) with respectextent to an ATM offering program under which the Company could have issuedCOVID-19 pandemic will directly or indirectly impact the Company’s business, results of operations and sold, from timefinancial condition, including current and future clinical trials and research and development costs, will depend on future developments that are highly uncertain, including as a result of new information that may emerge concerning COVID-19, the actions taken to time at its sole discretion, sharescontain or treat it, and the duration and intensity of its common stock, in an aggregate offering amountthe related effects.

2. Summary of up to $50.0 million. As of March 31, 2019, the Company had sold an aggregate of 3,475,166 shares of its common stock for total net proceeds of approximately $21.6 million under the ATM program. Effective April 7, 2019, the Company terminated this ATM offering program.Significant Accounting Policies

9


2.

Summary of Significant Accounting Policies

Unaudited Interim Financial Information

The condensed balance sheet as of December 31, 20192020 was derived from audited financial statements but does not include all disclosures required by accounting principles generally accepted in the United States of America (“GAAP”). The accompanying condensed financial statements, as of March 31, 20202021 and for the three months ended March 31, 2020,2021, are unaudited and have been prepared by the Company pursuant to the rules and regulations of the Securities and Exchange Commission (the “SEC”) for interim financial statements. Certain information and footnote disclosures normally included in financial statements prepared in accordance with GAAP have been condensed or omitted pursuant to such rules and regulations. The Company believes that the disclosures are adequate to make the information presented not misleading. These unaudited condensed financial statements should be read in conjunction with the Company’s audited financial statements and the notes thereto for the year ended December 31, 20192020 included in the Company’s Annual Report on Form 10-K for the year ended December 31, 20192020 filed with the SEC on March 10, 2020.31, 2021. In the opinion of management, all adjustments, consisting only of normal recurring adjustments as necessary for thea fair statement of the Company’s condensed consolidated financial position as of March 31, 2020,2021 and condensed consolidated results of its operations for the three months ended March 31, 2020, and cash flows for the three months ended March 31, 2021 and 2020 have been made. The results of operations for the three months ended March 31, 20202021 are not necessarily indicative of the results of operations tothat may be expected for the year ending December 31, 2020.2021.

Summary of Significant Accounting Policies

The Company’s significant accounting policies, which are disclosed in the audited consolidated financial statements for the year ended December 31, 20192020 and the notes thereto, are included in the Company’s Annual Report on Form 10-K that was filed with the SEC on March 10, 2020.31, 2021. There were no changes to significant accounting policies during the three months ended March 31, 2020, except for the items noted below.2021.

Risks and Uncertainties

The Company is monitoring the potential impact of COVID-19, if any, on the carrying value of certain assets. To date, the Company has not experienced material business disruption, nor has it incurred impairment of any assets as a result of COVID-19. The extent to which these events may impact the Company’s business, clinical development and regulatory efforts, and the value of its common stock, will depend on future developments, which are highly uncertain and cannot be predicted at this time. The duration and intensity of these impacts and resulting disruption to the Company’s operations is uncertain and the Company will continue to assess the financial impact

In addition, the Company is subject to other challenges and risks specific to its business and its ability to execute on its business plan and strategy, as well as risks and uncertainties common to companies in the biopharmaceutical industry with development and commercial operations, including, without limitation, risks and uncertainties associated with: obtaining regulatory approval of its late-stage product candidates; delays or problems in obtaining clinical supply, loss of single source suppliers or failure to comply with manufacturing regulations; identifying, acquiring or in-licensing additional products or product candidates; biopharmaceutical product development and the inherent uncertainty of clinical success; and the challenges of complying with applicable regulatory requirements.  In addition, to the extent the ongoing COVID-19 pandemic adversely affects our business and results of operations, it may also have the effect of heightening many of the other risks and uncertainties discussed above.

Use of Estimatesestimates

The preparation of financial statements in conformity with GAAP requires management to make estimates and assumptions that affect the reported amounts of assets and liabilities, the disclosure of contingent assets and liabilities at the date of the financial statements and the reported amounts of revenue and expenses during the reporting periods. Significant estimates and assumptions reflected in these condensed consolidated financial statements include, but are not limited to, revenue recognition, the accrual forof research and development expenses, the valuation of common units prior to the Merger and the valuation of common stockstock/unit-based awards. The Company bases its estimates on historical experience, known trends and other market-specific or other relevant factors that it believes to be reasonable under the derivative liability. Estimatescircumstances. On an ongoing basis, management evaluates its estimates as there are periodically reviewed in light of changes in circumstances, facts, and experience. Changes in estimates are recorded in the period in which they become known. Actual results couldmay differ from those estimates.estimates or assumptions.

Recently IssuedFair value measurements

Certain assets and Adopted Accounting Pronouncementsliabilities are carried at fair value under GAAP. Fair value is defined as the exchange price that would be received for an asset or paid to transfer a liability (an exit price) in the principal or most advantageous market for the asset or liability in an orderly transaction between market participants on the measurement date. Valuation techniques used to measure fair value must maximize the use of observable inputs and minimize the use of unobservable inputs. Financial assets and liabilities carried at fair value are to be classified and disclosed in one of the following three levels of the fair value hierarchy, of which the first two are considered observable and the last is considered unobservable:

ASU No. 2018-13, Fair Value Measurement (Topic 820): Changes

Level 1 — Quoted prices in active markets for identical assets or liabilities.

Level 2 — Observable inputs (other than Level 1 quoted prices), such as quoted prices in active markets for similar assets or liabilities, quoted prices in markets that are not active for identical or similar assets or liabilities, or other inputs that are observable or can be corroborated by observable market data.

Level 3 — Unobservable inputs that are supported by little or no market activity and that are significant to determining the fair value of the assets or liabilities, including pricing models, discounted cash flow methodologies and similar techniques.

The Company’s cash equivalents and marketable securities are carried at fair value, determined according to the Disclosure Requirements for Fair Value Measurementfair value hierarchy described above (see Note 3). The carrying values of the Company’s accounts payable and accrued expenses approximate their fair values due to the short-term nature of these liabilities. The carrying value of the Company’s long-term debt under its loan and security agreement approximates its fair value due to its variable interest rate.

Recently issued accounting pronouncements

In August 2018,December 2019, the FASB issued ASU No. 2018-13, Disclosure Framework – Changes2019-12,Income Taxes—Income Taxes (Topic 740): Simplifying the Accounting for Income Taxes (“ASU 2019-12”). ASU 2019-12 simplifies the accounting for income taxes by removing certain exceptions to the Disclosure Requirements for Fair Value Measurement (“ASU 2018-13”). The new standard modifies the disclosure requirements on fair value measuregeneral principles in Topic 820, including removals740. The amendments also improve consistent application of and simplify GAAP for other areas of Topic 740 by clarifying and amending existing disclosures, modifications of existing disclosures, and additions of new disclosures. Certain amendments on changes in unrealized gains and losses, the range and weighted average of significant unobservable inputs used to develop Level 3 fair values measurements, and the narrative description of measurement uncertainty should be applied prospectively for only the most recent interim of annual period presented in the initial fiscal year of adoption. All other amendments should be

10


applied retrospectively to all periods presented upon their effective date. Early adoption is permitted for any removed or modified disclosure. The new standardguidance. ASU 2019-12 is effective for thepublic business entities for fiscal years, and interim periods within those fiscal years, beginning after December 15, 2020. The Company onadopted this standard as of January 1, 2020.2021, and depending on the amendment, adoption was applied on a retrospective, modified retrospective, or prospective basis. The adoption of this standard did not have a material impact on the Company’s condensed consolidated financial position or results of operations.statements and related disclosures.

Recently Issued Accounting Pronouncements

ASU No. 2016-13, Financial Instruments – Credit Losses (Topic 326): Measurement of Credit Losses on Financial Instruments

In June 2016,March 2020, the FASB issued ASU No. 2016-13,Accounting Standards Update (“ASU”) Financial Instruments - Credit Losses (Topic 326): Measurement2020-04—Facilitation of Credit Lossesthe Effects of Reference Rate Reform on Financial Instruments (“ASU 2016-13”)Reporting (ASC Topic 848). This authoritative guidance provides optional relief for companies preparing for the discontinuation of interest rates such as LIBOR, which is expected to be phased out at the end of calendar 2021, and applies to lease contracts, hedging instruments, held-to-maturity debt securities and debt arrangements that have LIBOR as the benchmark rate. This guidance can be applied for a limited time, as of the beginning of the interim period that includes March 12, 2020 or any date thereafter, through December 31, 2022. The guidance may no longer be applied after December 31, 2022. In January 2021, the FASB subsequently issued authoritative guidance that makes amendments to ASU 2016-13, which have the same effective date and transition datenew rules on accounting for reference rate reform. The amendments clarify that all derivative instruments affected by the changes to interest rates used for discounting, margining or contract price alignment, regardless of January 1, 2022, as the Company is a smaller reporting company. These standards require that credit losses be reported using anwhether they reference LIBOR, or another rate expected losses model rather than the incurred losses model that is currently used, and establishes additional disclosures related to credit risks. For available-for-sale debt securities with unrealized losses, these standards now require allowances to be recorded insteaddiscontinued as a result of reducing the amortized cost of the investment. These standards limit the amount of credit losses to be recognized for available-for-sale debt securities to the amount by which carrying value exceeds fair value and requires the reversal of previously recognized credit losses if fair value increases. Based on the composition of the Company’s investment portfolio and other financial assets, current market conditions and historical credit loss activity,reference rate reform, an entity may apply certain practical expedients in ASC Topic 848. The Company anticipates that the adoption of these standards isthe guidance will not expected to have a material impact on results of operations and related disclosures.

3.

Short-Term Investments

The following table summarizes the Company’s short-term investments as of March 31, 2020 and December 31, 2019 (in thousands):condensed consolidated financial statements

 

 

March 31, 2020

 

 

 

Amortized

Cost

 

 

Gross

Unrealized

Gains

 

 

Gross

Unrealized

Losses

 

 

Fair Value

 

U.S government-sponsored enterprise securities

 

$

16,455

 

 

$

29

 

 

$

 

 

$

16,484

 

U.S. treasury securities

 

 

7,255

 

 

 

14

 

 

 

 

 

 

7,269

 

 

 

$

23,710

 

 

$

43

 

 

$

 

 

$

23,753

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

December 31, 2019

 

 

 

Amortized

Cost

 

 

Gross

Unrealized

Gains

 

 

Gross

Unrealized

Losses

 

 

Fair Value

 

U.S government-sponsored enterprise securities

 

$

20,456

 

 

$

2

 

 

$

(1

)

 

$

20,457

 

U.S. treasury securities

 

 

23,996

 

 

 

7

 

 

 

(1

)

 

 

24,002

 

 

 

$

44,452

 

 

$

9

 

 

$

(2

)

 

$

44,459

 

Short-term investments represent holdings of available-for-sale debt securities and are reported at fair value with unrealized gains and losses reported net of taxes, if material, in other comprehensive income. The Company did not have any realized gains or losses on its short-term investments for the three months ended March 31, 2020 and 2019. There were no other-than-temporary impairments recognized for the three months ended March 31, 2020 and 2019.

11


4.3. Fair Value of Financial AssetsMeasurements and LiabilitiesMarketable Securities

The following tables present information about the Company’s financialfair value hierarchy for its assets and liabilities, which are measured at fair value on a recurring basis and indicate the level of the fair value hierarchy utilized to determine such fair values (in thousands):

 

 

 

Fair Value Measurements as of March 31, 2020 using:

 

 

 

Level 1

 

 

Level 2

 

 

Level 3

 

 

Total

 

Assets:

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Cash equivalents:

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Money market funds

 

$

32,873

 

 

$

 

 

$

 

 

$

32,873

 

Short-term investments:

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

U.S. government-sponsored enterprise securities

 

 

 

 

 

16,484

 

 

 

 

 

 

16,484

 

U.S. treasury securities

 

 

 

 

 

7,269

 

 

 

 

 

 

7,269

 

 

 

$

32,873

 

 

$

23,753

 

 

$

 

 

$

56,626

 

Liabilities:

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Derivative liability

 

$

 

 

$

 

 

$

3

 

 

$

3

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Fair Value Measurements as of December 31, 2019 using:

 

 

 

Level 1

 

 

Level 2

 

 

Level 3

 

 

Total

 

Assets:

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Cash equivalents:

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Money market funds

 

$

23,906

 

 

$

 

 

$

 

 

$

23,906

 

Short-term investments:

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

U.S. government-sponsored enterprise securities

 

 

 

 

 

20,457

 

 

 

 

 

 

20,457

 

U.S. treasury securities

 

 

 

 

 

24,002

 

 

 

 

 

 

24,002

 

 

 

$

23,906

 

 

$

44,459

 

 

$

 

 

$

68,365

 

Liabilities:

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Derivative liability

 

$

 

 

$

 

 

$

3

 

 

$

3

 

   Fair Value Measurements at March 31, 2021 Using: 
   Level 1   Level 2   Level 3   Total 

Assets:

        

Cash equivalents:

        

Money market funds

  $51,059   $—     $ —     $51,059 

Marketable securities:

        

Commercial paper

   —      10,771    —      10,771 
  

 

 

   

 

 

   

 

 

   

 

 

 
  $51,059   $10,771   $—     $61,830 
  

 

 

   

 

 

   

 

 

   

 

 

 
   Fair Value Measurements at December 31, 2020 Using: 
   Level 1   Level 2   Level 3   Total 

Assets:

        

Cash equivalents:

        

Money market funds

  $77,129   $—     $—     $77,129 

Commercial paper

   —      1,800    —      1,800 

Marketable securities:

        

Commercial paper

   —      4,498    —      4,498 
  

 

 

   

 

 

   

 

 

   

 

 

 
  $77,129   $6,298   $—     $83,427 
  

 

 

   

 

 

   

 

 

   

 

 

 

DuringMarketable securities were valued by the periods ended March 31, 2020 and December 31, 2019, there were no transfers between Level 1, Level 2 and Level 3.

The derivative liability relates to a cash settlement option associated with the change of control provisionCompany using quoted prices in the Company’s Cystic Fibrosis Foundation, Inc. (“CFF”) agreement,active markets for similar securities, which meets the definition of a derivative. The fair value of the derivative liability is based on significant inputs not observable in the market, which representsrepresent a Level 32 measurement within the fair value hierarchy. The fair value of the derivative instrument was determined using the Monte-Carlo simulation analysis. In determining the fair value of the derivative liability, the inputs impacting fair value include the fair value of the Company’s common stock, expected term of the derivative instrument, expected volatility of the common stock price, risk-free interest rate, expected sales-based milestone payments, discount rate, probability of a change of control event, and the probability that the counterparty would elect to accept the alternative cash payment in lieu of its right to the future sales-based milestone payments. The fair value of the derivative liability was not material at March 31, 2020 and December 31, 2019.

5.Prepaids and Other Current Assets

Prepaids and other current assetsMarketable securities by security type consisted of the following (in thousands):

 

 

 

March 31,

 

 

December 31,

 

 

 

2020

 

 

2019

 

Prepaid clinical, manufacturing and scientific expenses

 

$

429

 

 

$

767

 

Prepaid insurance expenses

 

 

1,629

 

 

 

125

 

Other prepaid expenses and other current assets

 

 

431

 

 

 

512

 

 

 

$

2,489

 

 

$

1,404

 

   March 31, 2021 
   Amortized
Cost
   Gross
Unrealized
Gains
   Gross
Unrealized
Losses
   Fair
Value
 

Commercial paper

  $10,771   $ —     $ —     $10,771 
  

 

 

   

 

 

   

 

 

   

 

 

 
    $—     $—     
  

 

 

   

 

 

   

 

 

   

 

 

 
   December 31, 2020 
   Amortized
Cost
   Gross
Unrealized
Gains
   Gross
Unrealized
Losses
   Fair
Value
 

Commercial paper

  $4,498   $—     $—     $4,498 
  

 

 

   

 

 

   

 

 

   

 

 

 
  $4,498   $—     $—     $4,498 
  

 

 

   

 

 

   

 

 

   

 

 

 

The Company’s marketable securities are due within one year.

4. Collaboration Agreement

12In June 2020, the Company entered into an exclusive license and research collaboration agreement (the “Collaboration Agreement”) with Merck Sharp & Dohme Corp. (“Merck”) to support the research, development and commercialization of products for the treatment of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar dementia (FTLD). Pursuant to the Collaboration Agreement, the Company granted Merck an exclusive, worldwide license with the right to grant and authorize sublicenses, under certain intellectual property rights related to two certain undisclosed targets in connection with the Company’s ALS and FTLD programs to make, have made, use, import, offer to sell and sell compounds and products covered by such intellectual property rights. In the event that the exploitation of such compound or product would infringe during the term of the Merck Collaboration Agreement a claim of an issued patent controlled by Yumanity, Yumanity also granted Merck a non-exclusive, sublicensable, royalty-free license under such issued patent to exploit such compound and product.


Under the terms of the Collaboration Agreement, the Company and Merck are each responsible to perform certain research activities in accordance with a mutually agreed upon research plan. Upon the completion of certain stages of the research plan, Merck will elect to either advance and make certain contractual option payments or terminate the applicable research program. If Merck elects not to advance a research program, such program terminates and the rights granted to Merck in the program revert to the Company. Following completion of the research program, Merck is responsible for the development and commercialization of the compounds developed pursuant to the research program and any product containing such compounds.

Under the terms of the Collaboration Agreement, the Company received an upfront payment totaling $15.0 million in July 2020 and is eligible to receive up to $280.0 million upon achievement of specified research and development milestones, and up to $250.0 million upon achievement of specified sales- based milestones as well as a tiered, mid-single digit royalty on net sales of licensed products, subject to customary reductions.

Unless terminated earlier, the Collaboration Agreement will continue in full force and effect until one or more products has received marketing authorization and, thereafter, until expiration of all royalty obligations under the Collaboration Agreement. The Company or Merck may terminate the Collaboration Agreement upon an uncured material breach by the other party or insolvency of the other party. Merck may also terminate the Merck Collaboration Agreement for any reason upon certain notice to the Company.

Merck also participated in the Company’s Class C preferred units financing in June 2020 with terms consistent with those of other investors that purchased Class C preferred units in June 2020. The Class C preferred units were issued at a price of $4.0008 per unit, which was determined to be fair value based on the same price paid by other investors that purchased Class C preferred units in the financing. The equity investment was considered to be distinct from the Collaboration Agreement.

The Company assessed the promised goods and services to determine if they are distinct. Based on this assessment, the Company determined that Merck cannot benefit from the promised goods and services separately from the others as they are highly interrelated and therefore not distinct. Accordingly, the promised goods and services represent one combined performance obligation and the entire transaction price was allocated to that single combined performance obligation. The performance obligation is being satisfied over the research term as the Company performs the research and development activities through the first substantive option period, and participates in a Joint Steering Committee to oversee research and development activities. Accordingly, the upfront payment of $15.0 million was recorded as deferred revenue and will be recognized as revenue as the performance obligation is satisfied. The Company recognizes revenue using the cost-to-cost method, which it believes best depicts the transfer of control to the customer. Under the cost-to-cost method, the extent of progress towards completion is measured based on the ratio of actual costs incurred to the total estimated costs expected upon satisfying the identified performance obligation. Under this method, revenue is recorded as a percentage of the estimated transaction price based on the extent of progress towards completion. As of March 31, 2021, the aggregate amount of the transaction price related to the unsatisfied portion of the performance obligation is $4.6 million, which is

6.

expected to be recognized as revenue within the next year. For the three months period ended March 31, 2021, the Company recorded $3.5 million of collaboration revenue related to the Collaboration Agreement. At contract inception, the potential milestone payments that the Company is eligible to receive were excluded from the transaction price as they were fully constrained. At the end of each reporting period, the Company reevaluates the transaction price and as uncertain events are resolved or other changes in circumstances occur, and if necessary, the Company will adjust its estimate of the transaction price. Any additions to the transaction price would be reflected in the period as a cumulative revenue catch-up. At the inception of the arrangement, the Company evaluated the options held by Merck to either advance or terminate the applicable research program to determine if they provided Merck with any material rights. The Company concluded that the options were not issued at a significant and incremental discount, and therefore do not provide Merck with a material right. As such, these options were excluded as performance obligations and will be accounted for if and when they occur.

The Company assessed the Collaboration Agreement to determine whether a significant financing component exists and concluded that a significant financing component does not exist.

5. Accrued Expenses

Accrued Expenses

Accrued expenses consisted of the following (in thousands):

 

 

 

March 31,

 

 

December 31,

 

 

 

2020

 

 

2019

 

Accrued research and development expenses

 

$

3,127

 

 

$

3,186

 

Accrued payroll and related expenses

 

 

1,118

 

 

 

3,203

 

Accrued professional fees

 

 

429

 

 

 

397

 

Accrued other

 

 

51

 

 

 

78

 

 

 

$

4,725

 

 

$

6,864

 

   March 31,   December 31, 
   2021   2020 

Accrued employee compensation and benefits

  $585   $4,295 

Accrued external research and development expenses

  $1,531    1,780 

Accrued professional fees

  $1,001    987 

Other

  $432    789 
  

 

 

   

 

 

 
  $3,549   $7,851 
  

 

 

   

 

 

 

6. Debt

Long-term debt consisted of the following (in thousands):

 

   March 31,   December 31, 
   2021   2020 

Principal amount of long-term debt

  $15,000   $16,123 

Less: Current portion of long-term debt

   (3,675   (2,891
  

 

 

   

 

 

 

Long-term debt, net of current portion

   11,325    13,232 

Debt discount, net of accretion

   (365   (348

Accrued end-of-term payment

   453    353 
  

 

 

   

 

 

 

Long-term debt, net of discount and current portion

  $11,413   $13,237 
  

 

 

   

 

 

 

The Company has outstanding borrowings of $15.0 million (“Tranche 1”) under a loan and security agreement entered into in December 2019 (the “Term Loan”) with Hercules Capital, Inc. (the “Lender”). The Company may borrow an additional $5.0 million upon the occurrence of a development milestone and an equity event as defined in the agreement (“Tranche 2”), and an additional $10.0 million may become available to be drawn upon lender approval. Borrowings under the Term Loan are repayable in monthly interest-only payments until August 1, 2021, with the option to extend an additional six months upon the drawdown of Tranche 2. The interest-only period will be followed by monthly payments of equal principal plus interest until the loan maturity date of January 1, 2024. Outstanding borrowings bear interest at the greater of i) 8.75% and ii) the prime rate as reported in the Wall Street Journal plus 4.00%. A final payment fee of 5.25% of the amounts drawn under the Term Loan is due upon the earlier of the maturity date or the repayment date if paid early, whether voluntary or upon acceleration due to default. The Company may repay the Term Loan at any time by paying the outstanding principal balance in full, along with any unpaid accrued interest, the final payment fees of 5.25% of the amounts drawn and a prepayment fee calculated on amounts being prepaid. The prepayment fee is 3.0% if the Term Loan is repaid within the one-year anniversary of the draw date, 2.0% if paid between the first and second-year anniversary of the draw date and 1.0% if paid after the second anniversary of the draw date but before the maturity date.

In April 2020, the Term Loan was amended to permit indebtedness consisting of a loan under the Paycheck Protection Program (“PPP”) of the Coronavirus Aid, Relief, and Economic Security Act (the “CARES Act”) provided that such loan shall be unsecured, shall not contain any terms or conditions that are adverse to the Lender’s rights under the loan and that the Company will not prepay such loan. In June 2020, the Term Loan was amended and an additional final payment fee of $0.3 million became due upon repayment of the loan.

7.

On December 22, 2020, the Company entered into an Unconditional Secured Guaranty and Pledge Agreement (the “Guaranty”) with the Lender as a condition to the Lender’s consent to the Merger under the Term Loan between Yumanity, Inc. as borrower and the Lender. Immediately prior to the Merger, Yumanity, Inc. entered into a Fourth Amendment and Consent to Loan and Security Agreement dated as of December 22, 2020 with the Lender (the “Loan Amendment”). The Guaranty provides for the Company’s guaranty of Yumanity Inc.’s obligations under the Loan Agreement and provides the Lender a security interest in all of Company’s assets other than intellectual property as collateral. The Loan Amendment provides for the Lender’s consent to the Merger and to the creation and funding of a Silicon Valley Bank Paycheck Protection Program escrow account to hold funds in connection with Yumanity’s outstanding Paycheck Protection Program loan amounts for which Yumanity has submitted a forgiveness application. The Loan Amendment also amends the definition of “Change in Control” to include the situations in which the Company no longer controls Yumanity, Inc. The remaining terms and conditions of the Loan Agreement generally continue in the form existing prior to the Loan Amendment.

Short-Term Borrowings

As of March 31, 2021 and December 31, 2020, the interest rate applicable to borrowings under the Term Loan was 8.75%. For the three months ended March 31, 2021, the weighted average effective interest rate on outstanding borrowings under the Term Loan was approximately 3.22%.

On March 29, 2021, the Term Loan was amended again to allow for the creation of a new foreign subsidiary, as well as changing certain covenants related to the financial operations of said subsidiary. The subsidiary was formed on April 23, 2021.

Borrowings under the Term Loan are collateralized by substantially all of the Company’s personal property, other than its intellectual property. There were no financial covenants associated with the Term Loan; however, the Company is subject to certain affirmative and negative covenants restricting the Company’s activities, including limitations on dispositions, mergers or acquisitions; encumbering its intellectual property; incurring indebtedness or liens; paying dividends; making certain investments; and engaging in certain other business transactions. The obligations under the Term Loan are subject to acceleration upon the occurrence of specified events of default, including a material adverse change in the Company’s business, operations or financial or other condition. Upon the occurrence of an event of default and until such event of default is no longer continuing, the annual interest rate will be 5.0% above the otherwise applicable rate.

In April 2020, prior to entering into the Merger Agreement with PTI in August 2020, the Company had short-term borrowingsissued a Promissory Note to Silicon Valley Bank, pursuant to which it received loan proceeds of $1.1 million consisting of a Commercial Insurance Premium Finance and Security Agreement (the “Finance and Security Agreement”“Loan”) entered into on February 27, 2020. The Finance and Security Agreement has a ten-month repayment period with an annual interest rate of 2.59% and a maturity of December 11, 2020. Collateralprovided under the FinancePPP established under the CARES Act and Security Agreement includesguaranteed by the right, title and interestU.S. Small Business Administration. On April 3, 2021, the Company was notified by Silicon Valley Bank that the Loan forgiveness application was accepted by the Small Business Association as of March 30, 2021. Accordingly, the Company has recognized $1.1 million in certain business insurance policies. income for debt extinguishment.

As of March 31, 2020,2021, future principal payments due are as follows (in thousands):

Year

  Aggregate Minimum
Payments
 

2021

  $2,268 

2022

   5,805 

2023

   6,341 

2024

   586 

2025

   —   
  

 

 

 
  $15,000 
  

 

 

 

7. Stock/Equity-Based Compensation

Restricted Stock Units (RSUs)

On February 1, 2021, the Company’s board approved payment to be made to Company employees through a grant of RSUs based on the February 1, 2021 closing share price of the Company’s common stock with a fair value of $2.2 million. The requisite service period for the awards ranges from one to four years (the vesting period). The Company recognized employee stock-based compensation expense for the RSU grant on a straight-line basis over the vesting period of the awards. As of March 31, 2021, 122,419 RSUs were granted and the Company has paid less than $0.1recognized $0.3 million in interest on short-term borrowings.of stock-based compensation expense during the three months ended March 31, 2021.

8.

Stock-Based Compensation

2016 Stock Option and Incentive Plan

On February 3, 2016,

The following table summarizes the Company’s stockholders approvedRSU activity for the three months ended March 31, 2021:

   Units   Weighted
Average Grant
Date Fair Value
 

Unvested balance at December 31, 2020

   —     $—   

Issued

   122,469   $17.89 

Vested

   —     $—   

Forfeited

   (6,044  $17.89 

Unvested balance at March 31, 2021

   116,425   $17.89 

Summary of plans

Upon completion of the Merger, the Company assumed PTI’s 2016 Stock Option and Incentive Plan (the “2016 Plan”), and PTI’s 2016 Employee Stock Purchase Plan (the “2016 ESPP”).

2016 Stock Option and Incentive Plan

On February 3, 2016, PTI’s stockholders approved the 2016 Plan, which became effective on February 9, 2016. The 2016 Plan provides for the grant of incentive stock options, nonqualified stock options, stock appreciation rights, restricted stock units, restricted stock awards and other stock-based awards. The number of shares initially reserved for issuance under the 2016 Plan was 1,581,83979,092 shares. The number of shares of common stock that may be issued under the 2016 Plan will automatically increase each January 1, beginning January 1, 2017, by the lesser of 3% of the shares of the Company’s common stock outstanding on the immediately preceding December 31, or an amount determined by the Company’s board of directors or the compensation committee of the board of directors. The shares of common stock underlying any awards that are forfeited, canceled, repurchased, or are otherwise terminated by the Company under the 2016 Plan and the 2008 Equity Incentive Plan, as amended (the “2008 Plan”) will be added back to the shares of common stock available for issuance under the 2016 Plan. On January 1, 2020, an additional 1,563,49878,175 shares were reserved for issuance under the 2016 Plan. Options granted under the 2016 Plan with service-based vesting conditions generally vest over four years and expire after ten years. As of March 31, 2020,2021 the total number of shares of the Company’s common stock reserved for issuance under the 2016 Plan was 9,972,038 and the Company had 4,441,627626,100, of which 112,409 shares are available for future issuance under the 2016 Plan. The number of shares reserved for issuance under the 2016 Plan was increased by 303,495 shares effective as of January 1, 2021 in accordance with the provisions of the 2016 Plan described above.

2016 Employee Stock Purchase Plan

On February 3, 2016, the Company’sPTI’s stockholders approved the 2016 Employee Stock Purchase Plan (the “2016 ESPP”),ESPP, which became effective in connection with the completion of the Company’sPTI’s initial public offering. A total of 138,7576,938 shares of common stock were initially reserved for issuance under the 2016 ESPP. In addition, the number of shares of common stock that may be issued under the 2016 ESPP will automatically increase each January 1, beginning January 1, 2017, by the lesser of (i) 138,7576,938 shares of common stock, (ii) 1% of the Company’s shares of common stock outstanding on the immediately preceding December 31, or (iii) an amount determined by the Company’s board of directors or the compensation committee of the board of directors.

During the three months ended March 31, 2020, 31,027 shares of common stock were issued pursuant to the 2016 ESPP. As of MarchDecember 31, 2020, the total number of shares reserved under the 2016 ESPP was 580,74234,689 shares. The Company recognized less than $0.1 millionnumber of stock-based compensation during the three months ended March 31, 2020 related toshares reserved for issuance under the 2016 ESPP.ESPP was increased by 6,937 shares effective as of January 1, 2021 in accordance with the provisions of the 2016 ESPP described above.

RestrictedYumanity Therapeutics, Inc. Amended and Restated 2018 Stock Units (RSUs)Option and Grant Plan

On FebruaryDecember 4, 2020,2018, the Company’s board of directors adopted the 2018 Unit Option and Grant Plan (the “2018 Plan”), which was approved paymentby the Company’s members on December 5, 2018. The 2018 Plan provided for the Company to be madegrant unit options, restricted unit awards and unrestricted unit awards to employees, directors and consultants of the Company. As part of the Yumanity Reorganization and the Merger, the 2018 Plan was amended and restated as the “Yumanity Therapeutics, Inc. Amended and Restated 2018 Stock Option and Grant Plan”. Each stock option outstanding under the 2018 Plan at the Effective Time of the Merger was automatically converted into a nonemployee through a grantstock option exercisable for the same number of RSUsshares of Yumanity common stock, and then assumed by the Company, based on the February 4, 2020 closingExchange Ratio and the exercise price per share priceof such outstanding stock option, as adjusted for the Exchange Ratio. The 2018 Plan is administered by the board of directors or, at the discretion of the Company’s common stock.board of directors, by a committee of the board of directors. The grant did not meetexercise prices, vesting and other restrictions are determined at the criteria for liability classification as there was a fixeddiscretion of the board of directors, or its committee if so delegated.

Options granted under the 2018 Plan with service-based vesting conditions generally vest over four years and expire after ten years. The total number of common shares tothat may be issued and thereunder the 2018 Plan is no variability in1,527,210 as of March 31, 2021. Shares that are forfeited, canceled, reacquired by the numberCompany prior to vesting, satisfied without the issuance of shares which had been granted. The requisite service period foror otherwise terminated (other than by exercise) and units that are withheld upon the awards is from February 4, 2020exercise of an option or settlement of an award to August 4, 2020 (the vesting period). The Company recognized employee stock-based compensation expense forcover exercise price or tax withholding shall be added back to units available under the RSU grant on a straight-line basis over the vesting period of the awards.2018 Plan. As of March 31, 2020, 4,519 RSUs were2021, 435,628 shares remain available for issuance under the 2018 Plan.

Under each plan, the exercise price per option granted andis not less than the fair market value of common stock as of the date of grant.

Option valuation

The fair value of option grants is estimated using the Black-Scholes option-pricing model. Prior to the Merger, the Company recognized less than $0.1 millionwas a private company and lacks company-specific historical and implied volatility information. Therefore, it estimates its expected stock/unit volatility based on the historical volatility of stock-based compensation expense during the three months ended March 31, 2020.

13


a publicly traded set of peer companies. The following table summarizesexpected term of the Company’s RSU activityoptions has been determined utilizing a midpoint convention estimate. The risk-free interest rate is determined by reference to the U.S. Treasury yield curve in effect at the time of grant of the award for time periods approximately equal to the three months ended March 31, 2020:

 

 

Number

of Shares

 

 

Weighted

Average

Grant Date

Fair Value

 

Unvested balance at December 31, 2019

 

 

 

 

$

 

Granted

 

 

4,519

 

 

 

1.77

 

Vested

 

 

 

 

 

 

Forfeited

 

 

 

 

 

 

Unvested balance at March 31, 2020

 

 

4,519

 

 

$

 

Stock-Based Compensation

Stock-based compensation expense, including shares issuedexpected term of the award. Expected dividend yield is based on the fact that the Company has never paid cash dividends and does not expect to a nonemployee for consulting services, was classifiedpay any cash dividends in the statements of operations as follows (in thousands):foreseeable future.

 

 

Three Months Ended March 31,

 

 

 

2020

 

 

2019

 

Research and development

 

$

230

 

 

$

370

 

General and administrative

 

 

348

 

 

 

600

 

 

 

$

578

 

 

$

970

 

Option activity

The following table summarizes the Company’s stock option activity for theduring three months ended March 31, 2020 (in thousands except share and per share amounts):2021:

 

 

 

Number

of Shares

 

 

Weighted

Average

Exercise Price

Per Share

 

 

Weighted

Average

Remaining

Contractual

Term

 

 

Aggregate

Intrinsic Value

 

 

 

 

 

 

 

 

 

 

 

(Years)

 

 

 

 

 

Outstanding at December 31,

    2019

 

 

4,364,839

 

 

$

5.30

 

 

 

7.32

 

 

$

132

 

Granted

 

 

1,528,600

 

 

 

1.57

 

 

 

 

 

 

 

 

 

Forfeited

 

 

(363,028

)

 

 

6.34

 

 

 

 

 

 

 

 

 

Outstanding at March 31,

   2020

 

 

5,530,411

 

 

$

4.20

 

 

 

7.85

 

 

$

14

 

Exercisable at March 31,

   2020

 

 

2,509,969

 

 

$

5.79

 

 

 

6.48

 

 

$

5

 

Vested and expected to vest

   at March 31, 2020

 

 

5,447,161

 

 

$

4.23

 

 

 

7.96

 

 

$

14

 

   Number
of Shares
   Weighted
Average
Exercise
Price
   Weighted
Average
Remaining
Contractual
Term
   Aggregate
Intrinsic
Value
 
           (in years)   (in thousands) 

Outstanding as of December 31, 2020

   944,961   $20.70    8.29    6,522 

Granted

   528,075   $17.90    4.72    111 

Exercised

   —      —      —      —   

Forfeited

   (36,392  $14.11     

Outstanding as of March 31, 2021

   1,436,644   $19.79    7.77    7,338 

Vested and expected to vest as of March 31, 2021

   1,436,644   $19.79    7.77    7,338 

The aggregate intrinsic value of options is calculated as the difference between the exercise price of the options and the fair value of the Company’s common stock/units for those stock/unit options that had exercise prices lower than the fair value of the Company’s common stock/units.

The grant date fair value of options granted during the period was $1.7$6.5 million, or $1.10$12.39 per share on a weighted-average basis and will be recognized as compensation expense over the requisite service period ofranging from one to four years.

Stock/equity-based compensation

The Company recorded stock/equity-based compensation expense related to common stock/unit options and restricted units in the following expense categories in its condensed consolidated statements of operations (in thousands):

   Three Months Ended
March 31,
 
   2021   2020 

Research and development expenses

  $391   $226 

General and administrative expenses

   1,016    344 
  

 

 

   

 

 

 
  $1,407   $570 
  

 

 

   

 

 

 

As of March 31, 2020, there was $5.5 million of2021, total unrecognized compensation cost related to employeeunvested options and nonemployee unvestedrestricted common stock options granted under the 2016 Plan,was $10.0 million, which is expected to be recognized over a weighted-average remaining serviceweighted average period of 2.552.82 years. Stock compensation costs have not been capitalized by the Company.

Prior to 2013, the Company issued options to purchase 203,964 shares of common stock to nonemployees, primarily members of the Company’s scientific advisory board, that vest upon the achievement of specified development and clinical milestones. As of March 31, 2020, options for the purchase of 83,250 shares held by nonemployees remained unvested, pending achievement of the specified milestones.

8. Net Loss Per Share

9.

Significant Agreements

Genentech

In December 2018, the Company entered into a Technology Transfer and License Agreement (the “Genentech Agreement”) with Genentech, Inc. (“Genentech”) under which the Company granted Genentech an exclusive worldwide license for technology and

14


materials relating to potential therapeutic small molecule modulators of an undisclosed target within the proteostasis network. The rights do not include CFTR modulators and are unrelated to the Company’s investigational medicines or other ongoing research programs in cystic fibrosis. In connection with the terms of the Genentech Agreement, the Company is entitled to a nonrefundable cash payment of $5.0 million following the successful completion of the technology and materials transfer to Genentech and future milestone payments in the aggregate of approximately $96.0 million upon the achievement of specified development, regulatory, and commercial milestones. In addition, Genentech is obligated to pay the Company tiered royalties in the low single-digits based on net sales of products covered by the licenses granted under the Genentech Agreement. There are no cancellation, termination, or refund provisions in the Genentech Agreement that contain material financial consequences to the Company. Unless earlier terminated, the Genentech Agreement continues in full force and effect until the passing or expiration of all royalty payment obligations. Reciprocal termination rights under the agreement include termination for breach and termination for bankruptcy. Genentech may terminate the Genentech Agreement in its entirety, for convenience, upon thirty days’ notice to the Company.

The Company evaluated the Genentech Agreement in accordance with the provisions of Accounting Standards Codification Topic 606, Revenue from Contracts with Customers (“ASC 606”). The Company’s obligations under the Genentech Agreement are the following promises: (i) exclusive license to certain intellectual property associated with a specific target and (ii) technology and materials transfer related to the intellectual property underlying the licensed technology. The Company determined that the exclusive license is not distinct from the associated technology and materials transfer because the customer cannot benefit from, or utilize, the license without the technology and materials transfer. Specifically, the Company concluded that the exclusive license is not capable of being distinct from the associated technology and materials transfer because Genentech does not have the knowledge or expertise to fully exploit potential product candidates without the accompanying technology and materials provided pursuant to the transfer, and no other third party can perform the transfer due to the Company’s proprietary knowledge and specialized expertise with respect to the licensed intellectual property. Accordingly, the Company concluded that these promises should be combined into a single performance obligation (the “License and Transfer Performance Obligation”).

As of March 31, 2020, the Company has measured the transaction price solely in reference to the $5.0 million payment due upon receipt of notice from Genentech regarding the satisfactory completion of the technology and materials transfer. None of the variable consideration payable under the arrangement has been included in the transaction price as of March 31, 2020. Through March 31, 2020, the Company has not achieved any research, development, regulatory, or commercial milestones, or earned any royalties under the Genentech Agreement. The Company utilizes “the most likely” amount method to estimate the amount of research, development, and regulatory milestone payments to be received. As part of the evaluation for the research and development milestone payments, the Company considers several factors including the stage of research and development of the compounds included in the arrangement, the risk associated with the remaining research and development work required to achieve the milestone, and the Company’s level of involvement in the research and development activities.

Regulatory milestone payments are triggered upon the first commercial sale following receipt of regulatory approval from the FDA or other global regulatory authorities; therefore, such amounts will be excluded from the transaction price until the associated regulatory approval is received. The commercial milestone payments and royalties are subject to the royalty recognition constraint whereby such amounts will be recognized as revenue upon the later of:  (i) when the related sales occur, or (ii) when the performance obligation to which some or all of the payment has been allocated has been satisfied, or partially satisfied, because the exclusive license is deemed to be the sole or predominant item to which the payments relate. As all performance obligations are satisfied, the Company will recognize royalty revenue at the date the sales occur. The Company did not adjust the promised amount of consideration for the effects of a significant financing component because the Company expects that the period between when the promised goods and services are transferred and when the customer pays for those goods and services will be one year or less. There were no changes in the transaction price for the three months ended March 31, 2020.  

The transaction price of $5.0 million allocated to the combined performance obligation was recognized as revenue in February 2019 at the point in time that Genentech provided notice regarding the satisfactory completion of the technology and materials transfer. Upon that successful execution of the technology and materials transfer, control was deemed to be transferred for both the exclusive license and the technology and materials transfer promises, therefore the risks and rewards of ownership had been conveyed. As of March 31, 2020, the Company did not have any receivables or deferred revenue related to the Genentech Agreement because no payments under the arrangement became due, nor had the underlying performance obligation been satisfied.

10.

Income Taxes

The Company did not record a federal or state income tax benefit for its losses for the three months ended March 31, 2020 and 2019, respectively, due to the conclusion that a full valuation allowance is required against the Company’s deferred tax assets. All the Company’s losses before income taxes were generated in the United States.

15


11.

Net Loss per Share

Basic and diluted net loss per share was calculated as follows (in thousands, except share and per share amounts):

 

 

 

Three Months Ended March 31,

 

 

 

2020

 

 

2019

 

Numerator:

 

 

 

 

 

 

 

 

Net loss

 

$

(9,878

)

 

$

(14,418

)

Denominator:

 

 

 

 

 

 

 

 

Weighted average number of

   common shares outstanding—basic

   and diluted

 

 

52,146,633

 

 

 

50,976,907

 

Net loss per share—basic and diluted

 

$

(0.19

)

 

$

(0.28

)

   Three Months Ended
March 31,
 
   2021   2020 

Numerator:

    

Net loss

  $(8,682  $(7,465
  

 

 

   

 

 

 

Denominator:

    

Weighted average common shares/units outstanding, basic and diluted

   10,193,328    2,150,017 
  

 

 

   

 

 

 

Net loss per share/unit, basic and diluted

  $(0.85  $(3.47
  

 

 

   

 

 

 

The following common stock equivalents presented based on amounts outstanding at each period end, have been excluded from the computationcalculation of diluted weighted-average shares outstanding,net loss per share because such securitiesincluding them would have had an antidilutive impact:anti-dilutive impact:

 

 

March 31,

 

  As of March 31, 

 

2020

 

 

2019

 

  2021   2020 

Options to purchase common stock

 

 

5,530,411

 

 

 

4,564,427

 

   1,436,644    1,166,894 

Restricted stock units

 

 

4,519

 

 

 

 

Warrants to purchase common stock or shares convertible into common stock

   99,986    99,986 

 

 

5,534,930

 

 

 

4,564,427

 

  

 

   

 

 
   1,536,630    1,266,880 
  

 

   

 

 

12.9. Leases

The Company hasleased office and laboratory facilities in Cambridge, Massachusetts (the “Old Premises”) from an investor in the Company under a noncancelable operating lease that began in April 2015 and expired in March 2020. In February 2020, the Company amended the lease for the Old Premises to extend the lease expiration to April 30, 2020. The amendment was accounted for as a lease reassessment and the right-of-use asset and lease liability were remeasured at the reassessment date of February 2020 resulting in an increase of $0.1 million to the right-of-use asset for prepaid rent and a reduction of $0.1 million to the lease liability. In May 2020, the Company amended the lease for the Old Premises to extend the lease expiration to May 23, 2020 and recognized the final rent payment of less than $0.1 million in expense.

In February 2020, the Company entered into a license agreement with a third party for the use of office and laboratory space in Boston, Massachusetts, commencing in May 2020 (the “New Premises”). The Company determined that this license agreement qualified as a lease under ASC 842, Leases (“ASC 842”). The initial term of the license agreement is three years with the option to extend for its corporate headquartersa total of three one-year periods at fair-market rent at the time of each extension. In addition to use of office and laboratory space, the license fee includes various laboratory, office, and operational support services to be provided by the licensor. The initial monthly license fee escalates 3% annually and totals approximately $12.0 million for the three-year term. Additionally, the licensee agreement for the New Premises requires the Company to pay for a non-exclusive, irrevocable license to use forty-two unreserved parking spaces adjacent to the New Premises at the prevailing monthly parking rate. On May 1, 2020, the lease commencement date was met and the Company recorded an operating lease asset of $10.6 million and a corresponding lease liability of $10.2 million.

On December 22, 2020, as part of the Merger, the Company acquired a lease for approximately 30,000 square feet of office and laboratory space (the “Merger Premises”) in Boston, Massachusetts. The lease commenced in January 2018 andwith rent payments begancommencing in April 2018. This lease has a ten-yearThe initial term of the lease was ten years with anthe option to extend for an additional seven additional years.

The Company hasyears at fair-market rent at the right to terminate the lease in the eventtime of the inabilityextension. In addition to use theof office and laboratory space, due to substantial damage while the lessor has the right to terminate the lease if the Company defaults on the lease financial obligations. Per the termsis responsible for paying its allocable portion of the lease agreement, the Company does not have any residual value guarantees. In calculating the present value of the lease payments, the Company utilized its incremental borrowing rate based on electing the original lease term to account for each lease componentbuilding and its associated non-lease components as a single lease component. It has allocated all the contract consideration across lease components only. This may result in the initial and subsequent measurement of the balances of the right-of-use asset and lease liability for leases being greater than if the policy election was not applied. The Company’s real estate lease in Boston is considered a net lease, as the non-lease components (i.e., common area maintenance) are paidlaboratory operating expenses separately from rent, based on actual costs incurred. Therefore,Remaining fixed lease payments at the non-leasetime of the Merger were approximately $14.2 million. On December 22, 2020, the Company recorded an operating lease asset and corresponding lease liability of $10.2 million associated with this lease. The operating lease asset was increased by the value attributable to the below-market lease of $3.1 million and an allocated portion of the excess purchase price for the Merger of $1.9 million.

On January 7, 2021 the Company entered into a sublease agreement (the “Sublease”) with Moma Therapeutics, Inc. (the “Subtenant”), whereby the Company subleased the entire Merger Premises to the Subtenant. The initial term of the Sublease commences on the date the Company receives consent to the Sublease from the landlord and shall continue until 18 months from the commencement date. The Sublease provides for the first monthly installment of rent to be paid by the Subtenant on the date of the Sublease.

The Sublease provides for an initial annual base rent of $1,939,340, which increases annually up to a maximum annual base rent of $1,997,520. The Subtenant also is responsible for paying to the Company operating costs, annual tax costs and all utility costs attributable to the Premises during the term of the Sublease. Expense arising from the Merger Premises of $ 0.5 million for the three months ended March 31, 2021 and lease income from the Sublease of $0.3 million for the three months ended are classified in operating expense on a net basis.

The Company also leases property and equipment under agreements that are accounted for as finance leases.

The components of lease cost were as follows (in thousands):

   Three Months Ended
March 31,
 
   2021   2020 

Operating lease cost

  $1,666   $282 

Short-term lease cost

   —      —   

Variable lease cost

   77    160 

Finance lease cost:

    

Amortization of lease assets

   67    116 

Interest on lease liabilities

   3    7 
  

 

 

   

 

 

 

Total finance lease cost

  $70    123 
  

 

 

   

 

 

 

Supplemental disclosure of cash flow information related to leases was as follows (in thousands):

   Three Months Ended
March 31,
 
   2021   2020 

Cash paid for amounts included in the measurement of operating lease
liabilities (operating cash flows)

  $1,247   $291 

Cash paid for amounts included in the measurement of finance lease
liabilities (operating cash flows)

  $3   $7 

Cash paid for amounts included in the measurement of finance lease
liabilities (financing cash flows)

  $70   $88 

Operating lease liabilities arising from obtaining right-of-use assets

  $—     $—   

Finance lease liabilities arising from obtaining right-of-use assets

  $—     $—   

The weighted-average remaining lease term and discount rate were as follows:

   As of March 31, 
   2021  2020 

Weighted-average remaining lease term (in years) used for:

   

Operating leases

   4.88   0.25 

Finance leases

   1.25   1.19 

Weighted-average discount rate used for:

   

Operating leases

   9.02  8.11

Finance leases

   6.10  6.05

Because the interest rates implicit in the license agreement and lease agreement assumed from PTI were not includedreadily determinable, the Company’s incremental borrowing rate was used to calculate the present value of each. The present value of the Company’s finance leases was calculated using the rate implicit in the right-of-use asset and liability and are reflected as an expense in the period incurred.lease.

As of March 31, 2020,2021, future annual lease payments under the Company’s real estate operating leases and December 31, 2019, assets under operating lease were $12.3 million and $12.6 million, respectively. The elements of lease expenseequipment finance leases were as follows (in thousands):

 

 

 

For the Three Months Ended March 31,

 

 

 

2020

 

 

2019

 

Lease cost

 

 

 

 

 

 

 

 

Operating lease cost

 

$

462

 

 

$

462

 

Variable lease cost (1)

 

 

103

 

 

 

137

 

Total lease cost

 

$

565

 

 

$

599

 

 

 

 

 

 

 

 

 

 

Other information

 

 

 

 

 

 

 

 

Operating cash flows used for operating leases

 

$

425

 

 

$

414

 

Operating lease liabilities arising from obtaining

   right-of-use assets

 

$

12,921

 

 

$

14,000

 

Weighted-average remaining lease term

 

8 years

 

 

9 years

 

Weighted-average discount rate

 

 

4.50

%

 

 

4.50

%

Year

  Operating Leases   Finance Leases 

2021

  $4,527   $100 

2022

   6,173    49 

2023

   2,977    —   

2024

   1,931    —   

2025

   1,985    —   

Thereafter

   4,840    —   
  

 

 

   

 

 

 

Total future lease payments

   22,433    149 

Less: Imputed interest

   (4,538   (5
  

 

 

   

 

 

 

Total lease liabilities

  $17,895   $144 
  

 

 

   

 

 

 

The following table presents lease assets and liabilities and their classification on the condensed consolidated balance sheet (in thousands):

 

Leases

  

Condensed Consolidated Balance Sheet Classification

  Amount 

Assets:

    

Operating lease assets

  Operating lease right-of- use assets  $22,431 

Finance lease assets

  Property and equipment, net   132 
    

 

 

 

Total leased assets

    $22,563 
    

 

 

 

Liabilities:

    

Current:

    

Operating lease liabilities

  Operating lease liabilities  $4,611 

Finance lease liabilities

  Current portion of finance lease obligation   109 

Non-current:

    

Operating lease liabilities

  

Operating lease liabilities, net of current portion

   13,283 

Finance lease liabilities

  

Finance lease obligation, net of current portion

   35 
    

 

 

 

Total lease liabilities

    $18,038 
    

 

 

 

10. Commitments and Contingencies

License agreement

The Company has a tangible property and patent license agreement with Whitehead Institute for Biomedical Research (“Whitehead”) entered into in 2016 and subsequently amended in 2016 and 2018, under which the Company obtained a certain exclusive and non-exclusive, royalty-bearing, sublicensable, worldwide license to make, sell and distribute products under certain patents owned by Whitehead for certain know-how related to specific neurodegenerative diseases. In consideration for the rights granted by the agreement, the Company paid a one-time license fee of less than $0.1 million and issued 300,000 common units valued at $0.8 million. The Company is required to pay annual maintenance fees of up to $0.1 million through the termination of the agreement. The Company is also required to pay up to an aggregate of approximately $1.9 million upon the achievement of certain developmental and regulatory milestones for the first two licensed products under its first indication. The Company is also required to

(1)

The variable lease costs for the three months ended March 31, 2020 and 2019 include common area maintenance charges.  


Future leasepay additional milestone amounts for subsequent licensed products under its first or subsequent indications, but at a lower rate. The Company did not meet any milestones for the three months ended March 31, 2021 and the year ended December 31, 2020. The Company must also pay a royalty in the low single digits on future sales by the Company and a mid single to low double digit percentage of certain income received from sublicensees and certain partners. The license agreement remains in effect until the expiration of the last-to-expire patent licensed under the agreement. Whitehead may terminate the agreement upon the Company’s uncured material breach of the agreement, including failure to make required payments under the agreement or to achieve certain milestones, or if the Company becomes insolvent or bankrupt. The Company may terminate the license agreement at any time upon providing certain written notice to Whitehead.

Contingent Value Rights Agreement

In connection with the Merger, the Company entered into a Contingent Value Rights Agreement (the “CVR Agreement”) with Shareholder Representative Services LLC as representative of the PTI stockholders. The CVR Agreement entitles each holder of Company Common Stock as of immediately prior to the effective time of the Merger (the “Effective Time”) to receive certain net proceeds, if any, derived from the grant, sale or transfer of rights of the CF Assets ( the “CF Assets”) to any one of three specified counterparties completed during the 9-month period after the Effective Time (with any potential payment obligations continuing until the 10-year anniversary of the closing of the Merger Agreement). The CVR agreement became effective at Closing of the Merger and will continue in effect until the payment of all amounts payable thereunder or, if no CF Asset sale is completed, at the nine-month anniversary of the Effective Time. No liability has been recorded at March 31, 2021 and December 31, 2020 associated with the CVR’s as each of the three counterparties has expressed it is not interested in a transaction and so any related amounts are not considered probable or estimable.

Indemnification agreements

In the ordinary course of business, the Company may provide indemnification of varying scope and terms to vendors, lessors, contract research organizations, business partners and other parties with respect to certain matters including, but not limited to, losses arising out of breach of such agreements or from intellectual property infringement claims made by third parties. In addition, the Company has entered into indemnification agreements with members of its board of directors and its executive officers that will require the Company, among other things, to indemnify them against certain liabilities that may arise by reason of their status or service as directors or officers. The maximum potential amount of future payments the Company could be required to make under these indemnification agreements is, in many cases, unlimited. The Company has not incurred any material costs as a result of such indemnifications and is not currently aware of any indemnification claims.

Legal Matters

Between October 14 and December 7, 2020, following the announcement of the proposed merger among PTI, Yumanity, Inc. and Merger Sub, a wholly owned subsidiary of PTI, nine lawsuits were filed by purported stockholders of PTI challenging the Merger. The first lawsuit, brought as a putative class action, is captioned Aniello v. Proteostasis Therapeutics, Inc., et al., No. ncancelable leases1:20-cv-08578 (S.D.N.Y. filed Oct. 14, 2020). The remaining eight lawsuits, brought by the plaintiffs individually, are captioned Culver v. Proteostasis Therapeutics, Inc., et al., 1:20-cv-08595 (S.D.N.Y. filed Oct. 15, 2020); Donolo v. Proteostasis Therapeutics, Inc. et al., 1:20-cv-01400 (D. Del. filed Oct. 16, 2020); Straube v.Proteostasis Therapeutics, Inc., et al., 1:20-cv-08653 (S.D.N.Y. filed Oct. 16, 2020); Beck v. ProteostasisTherapeutics, Inc., et al., 1:20-cv-08783 (S.D.N.Y. filed Oct. 21, 2020); Dreyer v. Proteostasis Therapeutics, Inc., et al., 1:20-cv-05193 (E.D.N.Y. filed Oct. 28, 2020); Kopkin v. Proteostasis Therapeutics, Inc. et al., No. 1:20-cv-12103 (D. Mass. filed Nov. 23, 2020); Merritt v. Proteostasis Therapeutics, Inc., et al., No. 1:20-cv-10275 (S.D.N.Y. filed Dec. 6, 2020); and Koh v. Proteostasis Therapeutics, Inc., et al., No. 1:20-cv-10296 (S.D.N.Y. filed Dec. 7, 2020). All of the complaints named PTI and the individual members of PTI’s board of directors as defendants. The Aniello complaint also named Yumanity, Inc. as an additional defendant, and the Donolo complaint named Yumanity, Inc. and Merger Sub as additional defendants. The complaints asserted violations of Section 14(a) of the Securities Exchange Act of 1934, as amended, or the Exchange Act, and Rule 14a-9 promulgated thereunder against PTI and its directors, and violations of Section 20(a) of the Exchange Act against PTI’s directors. The Donolo complaint asserted an additional violation of Section 20(a) of the Exchange Act against Yumanity, Inc. The Aniello complaint asserted additional claims for breach of fiduciary duty against PTI’s directors and aiding and abetting against PTI and Yumanity, Inc.. The plaintiffs contended that the registration statement on Form S-4 filed by PTI with the Securities and Exchange Commission on September 23, 2020 (the “Registration Statement”) or the proxy statement/prospectus on Form 424B3 filed by PTI with the SEC on November 12, 2020 (the “Definitive Proxy”) omitted or misrepresented certain material information regarding the Merger. The complaints sought injunctive relief, rescission, or rescissory damages, dissemination certain information requested by the plaintiffs, and an award of plaintiffs’ costs, including attorneys’ fees and expenses. While PTI and Yumanity, Inc. believed that the disclosures set forth in the Registration Statement and Definitive Proxy complied fully with all applicable law and denied the allegations in the pending actions described above, in order to moot plaintiffs’ disclosure claims, avoid nuisance and possible expense and business delays, and provide additional information to its stockholders, on December 9, 2020, PTI filed a Form 8-K voluntarily to supplement certain disclosures in the Definitive Proxy related to plaintiffs’ claims with the supplemental disclosures (the “Supplemental Disclosures”). Following the filing of the Supplemental Disclosures, all of the actions discussed above were voluntarily dismissed by

the respective plaintiffs. On March 18, 2021, the parties executed a confidential fee and settlement agreement, pursuant to which all claims were released by plaintiffs and their counsel and an immaterial payment of a mootness fee will be paid to plaintiffs’ counsel, a portion of which will be paid by the Company’s insurer. On April 1, 2021 the mootness fee was paid by the Company.

11. Related Parties

There were no related party transactions for the three months ended March 31, 2021. The Company leased certain office and laboratory space from an investor in the Company until May 2020. Lease expense and amounts paid to the investor associated with this lease agreement for three months ended March 31, 2020 was $0.3 million and $0.9 million, respectively. There were no amounts payable to the investor as of March 31, 2020 (in thousands):2020.

Future Operating Lease Payments

 

 

 

 

2020

 

$

1,308

 

2021

 

 

1,780

 

2022

 

 

1,829

 

2023

 

 

1,880

 

2024

 

 

1,931

 

Thereafter

 

 

6,825

 

Total lease payments

 

 

15,553

 

Less: imputed interest

 

 

(2,632

)

Total operating lease liabilities

 

$

12,921

 

12. Subsequent Events

17On April 13, 2021, the Term Loan was amended to reduce the end-of-term charge from $0.3 million to $0.1 million and to extend the availability of Tranche 2 from March 31, 2021 to June 30, 2021.


Item 2.

Management’s Discussion and Analysis of Financial Condition and Results of Operations

Item 2. Management’s Discussion and Analysis of Financial Condition and Results of Operations.

The following discussion and analysis of our financial condition and the results of operations should be read in conjunction with our consolidated financial statements and related notes thereto includedappearing elsewhere in this Quarterly Report on Form 10-Q or Quarterly Report, and our audited financial statements included in our Annual Report on Form 10-K for the year ended December 31, 20192020 filed with the Securities and Exchange Commission, or the SEC on March 10, 2020, or the Annual Report.31, 2021. Some of the information contained in this discussion and analysis or set forth elsewhere in this Quarterly Report on Form 10-Q, including information with respect to our plans and strategy for our business, includes forward lookingforward-looking statements that involve risks and uncertainties. As a result of many factors, including those factors set forth in the “Risk Factors” section in our Annual Report and inof this Quarterly Report on Form 10-Q, our actual results could differ materially from the results described in, or implied by, the forward-looking statements contained in the following discussion and analysis. Such factors may be amplified by the COVID-19 pandemic and its potential impact on our business and the global economy.

Overview

We are a clinical stage biopharmaceutical company committed tofocused on the discovery and development of innovative, disease-modifying therapies for neurodegenerative diseases. Neurodegenerative diseases cause a progressive loss of structure and function in the brain, leaving patients with devastating damage to their nervous system and widespread functional impairment. Although treatments may help relieve some of the physical or mental symptoms associated with neurodegenerative diseases, few of the currently available therapies slow or stop the continued loss of neurons, resulting in a critical unmet need. We are specifically focused on developing novel therapeuticsdisease-modifying therapies to treat cystic fibrosis,devastating conditions, either with large or CF, through theratyping,orphan disease markets, including Parkinson’s disease, dementia with Lewy bodies, multiple system atrophy (“MSA”), amyotrophic lateral sclerosis (“ALS” (also known as Lou Gehrig’s disease)), frontotemporal lobar degeneration (“FTLD”), and Alzheimer’s disease.

Our goal is to advance one new program into the clinic every year. Our lead program, YTX-7739, is now in Phase 1 clinical trials for the potential treatment and disease modification of Parkinson’s disease. YTX-7739 targets an enzyme known as stearoyl-CoA desaturase (“SCD”). Inhibition of SCD in multiple cellular systems, including patient-derived neurons, as well as in a novel mouse model of Parkinson’s disease, has been demonstrated to overcome the toxicity of misfolded alpha-synuclein or the processα-synuclein, a protein strongly associated with Parkinson’s disease. We recently completed a Phase 1 single ascending dose (“SAD���) study of matching modulators to individual response to treatment regardless of CFTR mutations. CF is a disease caused by defectsYTX-7739 in the function or abundance of cystic fibrosis transmembrane conductance regulator, or CFTR protein. Although, CF is defined as a monogenic recessive genetic disorder caused by mutations in the CFTR gene, there ishealthy volunteers, which evaluated a broad range of disease activity for different organ systemsdoses of YTX-7739. We also completed a Phase 1a multiple ascending dose (“MAD”) study in CF, including lung disease, meconium ileus, diabetes,healthy volunteers, and liver disease, even for CF patients who are homozygous for the most common mutation, F508del mutation. In summary, CF genotype does not always match CF phenotype.

CFTR modulators are compounds that affect the synthesis, folding, trafficking, function, and clearanceannounced results in April 2021. A Phase 1b clinical study of CFTR protein and are potentially disease modifying. However, these modulators are only available to certain patient subsets based on genotype or a classification based on the ways in which they affect CFTR protein. They have been found to substantially improve patient health outcomes compared to best supportive care, although these drugs have variable efficacy among individuals as has been observed for most drugs.

In a clinical setting, when treatment efficacy is uncertain for individuals and when high costs limit “trial and error” approaches to assessing potential benefit for a patient from a specific drug, the new focus has become matching individuals with drugs that are most likely to be effective. Thus, emerging evidence and increased use of CF patient-derived cells studied in a laboratory test, such as the organoid assay, have been shown to provide a patient-friendly and cost-effective approach to increasing access to treatment for patients with CF and to optimize the risk-benefit ratio and cost-effectiveness of CFTR modulators. Currently, in many geographies, access to CFTR modulators has been limited because the approved drugs failed to meet cost-effectiveness thresholds required by payors.

Our CF-focused pipeline consists of novel CFTR modulators including correctors, potentiators and amplifiers. Upon discovery of amplifiers, a novel class of CFTR modulators, we utilized their novel mechanism of action as a drug screening tool and subsequently identified correctors and potentiators that we are now developing as combination therapies. We have completed double blind, randomized, placebo-controlled Phase 2 clinical trials with the combination of all three of our investigational CFTR modulators (PTI-801, or posenacaftor, a third generation CFTR corrector; PTI-808, or dirocaftor, a CFTR potentiator; and PTI-428, or nesolicaftor, a CFTR amplifier)YTX-7739 in patients with the most common F508del mutations. We are currently investigating combinations of posenacaftor, dirocaftor, and nesolicaftor in an ex vivo study to identify potential clinical responders among subjects with CF who have rare CFTR mutations. Based on the functional response to our investigational CFTR modulators in the ex vivo assay, we will invite select patients to participate in clinical trials with the drug candidates to validate the abilityParkinson’s disease has commenced as a continuation of the MAD study. The Phase 1b part of the study will assess safety, tolerability and pharmacokinetics of ex vivoYTX-7739 response to predict clinical benefit. If approved, we intend to commercialize our combination therapy for CF patients with rare CF mutations and as well as those who have at least a single copyproof of the F508del mutation.

In February 2019, we joined the HIT-CF consortium, a pan-European strategic initiative which seeks to validate a personalized therapy approach for CFbiology in patients with rare genetic mutationsParkinson’s disease by exploring biomarkers of target engagement. The study will also explore potential correlative clinical parameters such as electroencephalography and genotypes that make them ineligibleneuroimaging measurements to monitor for approved CFTR modulator therapies. Asearly effects of February 2020, HIT-CF has collected rectal biopsiesYTX-7739. Early results from over 500 subjects across European Cystic Fibrosis Society, or ECFS, Clinical Trial Network, or CTN, clinical sites out of a population of approximately 2,300 adultsthe Phase 1b part are anticipated in Europe alone who have rare CFTR genotypes. These tissue samplesmid-2021. Our second program, YTX-9184, also inhibits SCD but is chemically distinct from CF subjects with less-common genotypes are currently assayed as organoidsYTX-7739. Good Laboratory Practice (“GLP”) safety pharmacology and we are able to use these organoids to test responsiveness to our investigational CFTR modulators. We intend to initiate the CHOICES (Crossover trial based on Human Organoid Individual response in CF - Efficacy Study) trial, which we expect will be the first-ever personalized medicine-based trial in CF,toxicological studies for YTX-9184 were initiated in the second halfquarter of 2020. We plananticipate commencing the first in human studies of YTX-9184 in 2021 and intend to enroll patients in Europedevelop YTX-9184 for the potential treatment of dementia with CF who are ineligible for current standard of care CFTR modulator therapies due to their genotype. This trial,Lewy bodies, a devasting neurodegenerative disease which is financially supportedalso characterized by the European Commission,abnormal accumulation of aggregates of α-synuclein.

At the center of our scientific foundation is contemplatedour drug discovery engine, which is based on technology licensed from the Whitehead Institute, an affiliate of the Massachusetts Institute of Technology. This core technology, combined with investments and advancements by us, is designed to be a placebo-controlled, double blind, crossover studyenable rapid screening to identify drugs with the potential to modify disease by overcoming toxicity in disease-causing gene networks. Toxicity in many neurodegenerative diseases results from an 8-week treatment period and six monthsaberrant accumulation of uninterrupted dosing with posenacaftor, dirocaftor, and nesolicaftor. Beyond HIT-CF, other groups in multiple regions have created repositories of patient-derived cells, including organoids, that offer additional pools of patients for ex vivo profiling for response to PTI compounds and possible confirmatory clinical trials that would mirror the CHOICES study design. We have completed scientific advice meetings with Medicines and Healthcare Products Regulatory Agency (MHRA),misfolded proteins in the United Kingdom

18


brain. We leverage our proprietary discovery engine to identify and the Dutch Medicines Evaluation Board (MEB) on the CHOICES programscreen novel drug targets and drug molecules for the treatment of people living with CF.  In additiontheir ability to the positive scientific adviceprotect nerve cells from the MHRA and MEB, we received a High Strategic Fit scoretoxicity arising from the Clinical Trials Network (CTN) for the HIT-CF – CHOICES protocol.

Equity Financings and Research Funding

In addition to our wholly owned CF programs, in December 2018, we entered into a Technology Transfer and License Agreement, or the Genentech Agreement, with Genentech, Inc., or Genentech. We granted Genentech a worldwide, exclusive license for technology and materials relating to potential therapeutic small molecule modulators of an undisclosed target within the proteostasis network. The rights do not include CFTR modulators and are unrelated to our investigational products or other ongoing research programs in cystic fibrosis. In connection with the Genentech Agreement,misfolded proteins. To date, we have received an upfront payment, and are eligible to receive additional milestone payments,identified over 20 targets, most of which are approximately $96.0 million in the aggregate, subject to the achievement of specified development, regulatory, and commercial milestones. In addition, Genentech is obligated to pay us tiered royalties in the low single-digits based on net sales of products covered by the licenses granted under the Genentech Agreement.

Since our inception in 2006, we have devoted substantially all our resources to organizing and staffing our company, business planning, raising capital, acquiring and developing product and technology rights, and conducting research and development activities for our product candidates. We do not have any products approved for sale and have not generated any revenue from product sales.previously been linked to neurodegenerative diseases. We have fundedbelieve this discovery platform will allow us to replenish our operations to date with proceeds received from equity offerings,pipeline as programs graduate towards the issuance of convertible promissory notes and, to a lesser extent, payments received in connection with collaboration agreements and a research grant.clinic.

In May 2019, we entered into a sales agreement with H.C. Wainwright & Co., LLC, or HCW, with respect to an at-the-market, or ATM, offering program, or the HCW ATM program, under which we may issue and sell, from time to time at our sole discretion, shares of our common stock, in an aggregate offering amount of up to $56.6 million. HCW acts as our sales agent and will use commercially reasonable efforts to sell shares of common stock from time to time, based upon instruction from us. Common stock will be sold at prevailing market prices at the time of the sale, and as a result, prices may vary. We will pay HCW up to 3% of the gross proceeds from any common stock sold under the sales agreement. As of December 31, 2019, we have sold 987,653 shares of our common stock for total net proceeds of approximately $3.5 million under the HCW ATM program. We did not sell any shares of our common stock under the ATM program during the three months ended March 31, 2020.

Since our inception, we have not generated significant revenue and have incurred significant operating losses.losses since inception. Our ability to generate product revenue sufficient to achieve profitability will depend on the successful development and eventual commercialization of one or more of our current or future product candidates. Our net losses were $9.9$8.7 million and $14.4$7.5 million, respectively, for the three months ended March 31, 20202021 and 2019, respectively.2020. As of March 31, 2020,2021, we had an accumulated deficit of $346.5$156.5 million. We expect to continue to incur significant expenses and increasing operating losses for at least the next several years. We expect that our expenses and capital requirements will increase substantially in connection with our ongoing activities particularly if and as we:

expand and/successfully complete preclinical and clinical development of our product candidates;

successfully submit investigational new drug, or advance our proprietary combination therapy candidates, posenacaftor, dirocaftor, and nesolicaftor, into Phase 3 clinical trials;

seek regulatory approvalIND, applications or comparable applications, for our product candidates;

seek support and approvalidentify, assess or develop new product candidates from our collaboration partners, HIT-CF, the TDN, the CTN,discovery engine platform;

develop a sustainable and other interested parties;

hire personnel to support our product development,scalable manufacturing commercialization, and administrative efforts;

advance the research and development efforts of our CF and other product candidates, including, without limitation, back-up compounds; and

scale up our manufacturing processes and capabilities to support our ongoing preclinical activities and clinical trials ofprocess for our product candidates, as well as establish and commercialization ofmaintain commercially viable supply relationships with third parties that can provide adequate products and services to support clinical activities and commercial demand for our product candidates;

negotiate favorable terms in any of ourcollaboration, licensing, or other arrangements into which we may enter;

obtain regulatory approvals for product candidates for which we successfully complete clinical development;

launch and successfully commercialize product candidates for which we obtain regulatory approval, either by establishing a sales, marketing, approval.  and distribution infrastructure or collaborating with a partner;

negotiate and maintain an adequate price for our product candidates, both in the United States and in foreign countries where our products are commercialized;

obtain market acceptance of our product candidates as viable treatment options;

build out new facilities or expand existing facilities to support our ongoing development activity;

address any competing technological and market developments;

maintain, protect, expand, and enforce our portfolio of intellectual property rights, including patents, trade secrets, and know-how; and

attract, hire and retain qualified personnel.

We will not generate revenue from product sales unless and until we successfully complete clinical development and obtain regulatory approval for our product candidates. If we obtain regulatory approval for any of our product candidates and do not enter into a commercialization partnership, we expect to incur significant expenses related to developing our internal commercialization capability to support product sales, marketing, manufacturing and distribution. In addition, we will continuedistribution activities. We also expect to incur additional costs associated with operating as a public company.

19


As a result, we will need substantial additional funding to support our continuing operations and pursue our growth strategy. Until such time as we can generate significant revenue from product sales if ever,or additional licensing agreements, we expect to finance our operations through the sale of public or private equity offerings, debt financings or other capital sources, including potentialwhich may include collaborations with other companies or other strategic transactions. We may be unable to raise additional funds or enter into such other agreements or arrangements when needed on favorable terms, or at all. If we fail to raise capital or enter into such agreements as, and when, needed, we maycould have to significantly delay, scale back,reduce or discontinue theeliminate development and commercialization of one or more of our product candidates.candidates or delay our pursuit of potential in-licenses or acquisitions.

As of March 31, 2020, we had cash, cash equivalents and short-term investments of $57.1 million. We believe that our existing cash, cash equivalents, and short-term investments are sufficient to fund our projected operating expenses and capital requirements for at least the next 12 months. However, additional funding will be necessary to fund our MORE trial and to advance our proprietary combination therapy candidates through regulatory approval and into commercialization, if approved. We intend to obtain additional funding through public or private financing or collaborative arrangements with strategic partners to increase the funds available to support our operating and capital needs. Although we have been successful in raising capital in the past, there is no assurance that we will be successful in obtaining such additional financing on terms acceptable to us, if at all, nor is it considered probable under the accounting standards. The COVID-19 pandemic continues to rapidly evolve and has already resulted in a significant disruption of global financial markets. If the disruption persists and deepens, we may experience an inability to access additional capital, when and if needed. If we are unable to obtain funding, we would be forced to delay, reduce or eliminate our research and development programs, product portfolio expansion or commercialization efforts, which could adversely affect our business prospects, or we may be unable to continue operations. Because of the numerous risks and uncertainties associated with product development, we are unable to predict the timing or amount of increased expenses or when or if we will be able to achieve or maintain profitability. Even if we are able to generate product sales, we may not become profitable. If we fail to become profitable or are unable to sustain profitability on a continuing basis, then we may be unable to continue our operations at planned levels and be forced to reduce or terminate our operations.

Recent Developments

We expect to continue to incur significant operating losses for at least the next several years as we advance our product candidates through preclinical and clinical development, manufacture our product candidates for clinical or commercial use, and, ultimately, seek regulatory approval. In April 2020,addition, if we announced thatobtain marketing approval for any of our product candidates, we have completed scientific advice meetingsexpect to incur significant commercialization expenses related to product manufacturing, marketing, sales and distribution. We may also incur expenses in connection with the Dutch Medicines Evaluation Board,in-licensing or MEB,acquisition of additional product candidates.

As a result, until such time as we can generate significant revenue from product sales, if ever, we expect to finance our operations through public or private securities offerings, debt financings or other sources, which may include licensing, collaborations or other strategic transactions or arrangements. We may be unable to raise additional funds or enter into such other transactions or arrangements when needed on favorable terms, or at all. If we fail to raise capital or enter into such transactions or arrangements as and when needed, we may have to significantly delay, scale back or discontinue the CHOICES trialdevelopment and commercialization of one or more of our product candidates or delay our pursuit of potential in-licenses or acquisitions.

Biopharmaceutical product development is a highly speculative undertaking and involves a substantial degree of risk. Typically, it takes many years to develop one new product from the time it is discovered to when it is available for treating patients, and development may cease for a number of reasons. Because of the treatmentnumerous risks and uncertainties associated with product development, including any impact from the COVID-19 pandemic, we are unable to predict the timing or amount of people living with CF. The MEB is the Dutch regulatory agency responsible for assessing, monitoringincreased expenses or when or if we will be able to achieve or maintain profitability. Even if we are able to generate product sales, we may not become profitable. If we fail to become profitable or are unable to sustain profitability on a continuing basis, we may be unable to continue our operations at planned levels and promoting the proper usebe forced to reduce or terminate our operations.

As of medicines.March 31, 2021, we had cash, cash equivalents and short-term investments of $62.9 million. We believe that CHOICES isour existing cash, cash equivalents and short-term investments will enable us to fund our operating expenses and capital expenditure requirements into the first ever personalized medicine-based study in CF and will test PTI drug combinations in an ex vivo study and then in a clinical trial to assessthird quarter of 2022 from the predictabilitydate of issuance of the organoid assaycondensed consolidated financial statements included in this Quarterly Report. We have based this estimate on assumptions that may prove to be wrong, and we could exhaust our available capital resources sooner than we expect. See “— Liquidity and Capital Resources.” Our future viability beyond that point is dependent on our ability to raise additional capital to finance our operations.

COVID-19

In March 2020, COVID-19 was declared a global pandemic by the World Health Organization and to date, the COVID-19 pandemic continues to present a substantial public health and economic challenge around the world. The length of time and full extent to which the COVID-19 pandemic will directly or indirectly impact our business, results of operations and financial condition will depend on future developments that are highly uncertain, subject to change and difficult to predict. While we continue to conduct our research and development activities, the COVID-19 pandemic may cause disruptions that affect our ability to initiate and complete preclinical studies and clinical trials or to procure items that are essential for clinical benefit.

COVID-19 Business Update

Withour research and development activities. The pandemic has already caused significant disruptions in the global spreadfinancial markets, and may continue to cause such disruptions, which could impact our ability to raise additional funds to support our operations. Moreover, the pandemic has significantly impacted economies worldwide and could result in adverse effects on our business and operations. To date, we have not experienced material business disruptions or incurred impairment losses in the carrying values of our assets as a result of the ongoing COVID-19 pandemic inpandemic.

We plan to continue to closely monitor the first quarter of 2020, we implemented business continuity plans designed to address and mitigate theongoing impact of the COVID-19 pandemic on our employees and our business includingoperations. In an effort to provide a safe work environment for our clinical trials, supply chains and third-party providers.employees, we have, among other things, implemented measures to enable remote work whenever possible. We expect to continue to closely monitor the COVID-19 situationtake actions as may be required or recommended by government authorities or as we evolve our business continuity plans and response strategy. In March 2020, the Governor of Massachusetts ordered all individuals livingdetermine are in the Commonwealthbest interests of Massachusettsour employees and other business partners in light of the pandemic.

Merger with Proteostasis

On August 22, 2020, Proteostasis Therapeutics, Inc, a Delaware corporation (“Proteostasis”), Pangolin Merger Sub, Inc. (“Merger Sub”), Yumanity, Inc. (formerly Yumanity Therapeutics, Inc.), and Yumanity Holdings, LLC (“Holdings”), entered into the Merger Agreement, as amended on November 6, 2020, pursuant to staywhich Merger Sub merged with and into Yumanity, Inc. Immediately prior to the closing of the transaction, Holdings merged with and into Yumanity, Inc. with Yumanity, Inc. surviving the Merger (the “Yumanity Reorganization”) and, upon the closing of the Merger, Yumanity, Inc. became a wholly owned subsidiary of Proteostasis. The Merger was completed on December 22, 2020 pursuant to the terms of the Merger Agreement. In connection with the completion of the Merger, Proteostasis changed its name to Yumanity Therapeutics, Inc., and the trading symbol changed from “PTI” to “YMTX.” We refer to the historical operations of Holdings and Yumanity, Inc. as Yumanity and following the Merger, the business conducted by Yumanity became our primary business.

Pursuant to the terms of the Merger Agreement, upon closing of the Merger, all of Yumanity, Inc.’s outstanding common stock was exchanged for common stock of Proteostasis and all outstanding options and warrants to purchase common stock of Yumanity, Inc. were exchanged for options and warrants to purchase common stock of Proteostasis.

The transaction was accounted for as a reverse merger and as an asset acquisition in accordance with Generally Accepted Accounting Principles in the United States, or GAAP. Under this method of accounting, Yumanity was deemed to be the accounting acquirer for financial reporting purposes. This determination was primarily based on the facts that, immediately following the Merger: (i) Yumanity’s equity holders owned a substantial majority of the voting rights in the combined organization, (ii) Yumanity designated a majority of the members (7 of 9) of the initial board of directors of the combined organization and (iii) Yumanity’s senior management held all key positions in the senior management of the combined organization. Accordingly, for accounting purposes, the transaction was treated as the equivalent of Yumanity issuing stock to acquire the net assets of Proteostasis. As a result, as of the closing date of the Merger, the net assets of Proteostasis were recorded at their place of residence for an indefinite period of time (subject to certain exceptions to facilitate authorized necessary activities) to mitigateacquisition-date fair values in the impactfinancial statements of the COVID-19 pandemic so our workforce transitioned to working remotely. We are currently evaluating plans to reopen our office to allow employees to returnCompany and the reported operating results prior to the office, which will be based onMerger are those of Yumanity.

Private Placement

On December 14, 2020, we entered into a phased approach that is principles-based and local in design,subscription agreement with a focus on patient continuity, employee safety and optimal work environment. While we are experiencing limited financial impacts at this time, givencertain accredited investors for the global economic slowdown, the overall disruption of global healthcare systems and the other risks and uncertainties associated with the pandemic, our business, financial condition, results of operations and growth prospects could be materially adversely affected.

Clinical Development

With respect to clinical development, we have taken measures to implement remote and virtual approaches, including remote patient monitoring where possible, to maintain patient safety and trial continuity and to preserve study integrity. As the COVID-19 pandemic continues, we anticipate an impact on patient enrollment.  We could also see an impact on the ability to supply study drug, report trial results, or interact with regulators, ethics committees or other important agencies due to limitations in regulatory authority employee resources or otherwise.  In addition, we rely on contract research organizations or other third parties to assistsale by us with clinical trials, and we cannot guarantee that they will continue to perform their contractual duties in a timelyprivate placement of 1,460,861 shares of our common stock for a price of $23.00 per share. We refer to this sale herein as the Private Placement. The Private Placement closed on December 22, 2020. The aggregate gross proceeds for the issuance and satisfactory manner as a resultsale of the COVID-19 pandemic.  Ifcommon stock were $33.6 million and, after deducting certain of our expenses, the COVID-19 pandemic continues and persists for an extended period of time,net proceeds we could experience significant disruptions to our clinical development timelines, which would adversely affect our business, financial condition, results of operations and growth prospects.

Regulatory Activities

With respect to regulatory activities, it is possible that we could experience delaysreceived in the timing of review and/or our interactions with the FDA or the European Commission, or EC, due to, for example, absenteeism by governmental employees, inability to conduct planned physical inspections related to regulatory approval, or the diversion of efforts of the FDA or EC and attention to approval ofPrivate Placement were $31.6 million.

20


other therapeutics or other activities related to COVID-19, which could delay approval decisions with respect to the preparation and submission to the FDA of a new drug application, or NDA, or the preparation and submission to the EC of a Marketing Authorization Application, or MAA, and otherwise delay or limit our ability to make planned regulatory submissions or obtain new product approvals.Financial Operations Overview

Financial Impact

The COVID-19 pandemic continues to rapidly evolve and has already resulted in a significant disruption of global financial markets.  If the disruption persists and deepens, we could experience an inability to access additional capital, which could in the future negatively affect our operations.

Components of our Results of Operations

Revenue

To date, we have not generated any revenue from product sales and dodoes not expect to generate any revenue from the sale of products infor the foreseeable future. If our development efforts for product candidates are successful and result in regulatory approval or licenses with third parties, we may generate revenue in the future from product sales, milestone payments under our existing collaboration agreement or payments from other license agreements that we may enter into with third parties.

In June 2020, we entered into a research collaboration and license agreement (the “Collaboration Agreement”) with Merck Sharp & Dohme Corp. (“Merck”), focused on accelerating the development of new treatments for neurodegenerative diseases. Under the terms of the Collaboration Agreement, Merck will gain exclusive rights to two novel pipeline programs for the treatment of ALS and FTLD. We did not recognize any revenueand Merck will collaborate to advance the two preclinical programs during the three months ended March 31, 2020. Allresearch term, after which Merck has the right to continue clinical development and commercialization. Under the Collaboration Agreement, we received an upfront payment totaling $15.0 million and are eligible to receive future milestone payments of up to $530.0 million associated with the successful research, development and sales of marketed products for pipeline programs, as well as royalties on net sales. We will perform certain research and development activities over the research term pursuant to the Collaboration Agreement and will participate on a Joint Steering Committee to oversee research and development activities. We cannot provide assurance as to the timing of future milestone or royalty payments or that we will receive any of these payments at all.

We will record revenue over the research term as we satisfy our performance obligation under the Collaboration Agreement. Accordingly, the upfront payment of $15.0 million will be recognized as revenue duringusing the cost-to-cost method, which we believe best depicts the transfer of control to the customer. Under the cost-to-cost method, the extent of progress towards completion is measured based on the ratio of actual costs incurred to the total estimated costs expected upon satisfying the identified performance obligation. We recorded $3.5 million and $0 million of collaboration revenue for the three months ended March 31, 2019 was derived from our Genentech2021 and 2020, respectively, related to the Collaboration Agreement.

Operating Expenses

Research and Development Expenses

Research and development expenses which include costs of research services incurred in connection with our collaboration agreements and research grant, consist primarily of costs incurred in connection with the discovery, preclinical and clinical development and manufacture of our product candidates, whichand include:

employee-related expenses, including salaries, benefits, stock/equity-based compensation, consultants and other related benefits, travel, and stock-based compensation expensecosts for employees engagedindividuals involved in research and development functions;activities;

external research and development expenses incurred in connection with the preclinical and clinical development of our product candidates and under agreements with contract research organizations or CROs,(“CROs”), investigative sites and other scientific development services;

costs incurred under agreements with contract development and manufacturing organizations or CMOs;(“CDMOs”) for developing and manufacturing material for preclinical studies and clinical trials;

licensing agreements and associated milestones;

costs of research services incurred in connectionrelated to compliance with our collaboration agreement;regulatory requirements;

lab supplies and other lab related expenses; and

facilities, depreciation and other allocated expenses, which include direct and allocated expenses for rent, and maintenance of facilities, insurance and supplies; andother operating costs.

payments made under third-party licensing agreements.

We expense research and development costs as incurred. Weincurred and recognize external development costs based on an evaluation of the progress to completion of specific tasks using information provided to us by our service providers. This process involves reviewing open contracts and purchase orders, communicating with our personnel to identify services that have been performed on our behalf, and estimating the level of service performed and the associated cost incurred for the service when we have not yet been invoiced or otherwise notified of actual costs. Nonrefundable advance payments for goods and services to be received in the future for use in research and development activities are deferred and capitalized in prepaid expenses and other current assets. The capitalized amounts are expensed as the related goods are delivered or the services are performed. Upfront payments, milestone payments and annual maintenance fees under license agreements are expensed in the period in which they are incurred.

Our external direct research and development expenses are tracked on a program-by-program basisby product candidate and consist primarily of external costs such asthat include fees and other expenses paid to outside consultants, centralCROs, CDMOs and research laboratories contractors, CROs, and CMOs in connection with our clinical trials and preclinical development, process development, manufacturing and clinical development activities. Our direct research and development expenses by product candidate also include fees incurred under third-party license agreements. We do not allocate employee costs and costs associated with our platform technology, facility expenses,early stage discovery efforts, laboratory supplies and facilities, including depreciation or other indirect costs, to specific product development programscandidates because these costs are deployed across multiple product development programs and our platform and, as such, are not separately classified. We use internal resources to manage our preclinical

Research and development activities are central to our business model. Product candidates in later stages of clinical development generally have higher development costs than those in earlier stages of clinical development, primarily due to the increased size and perform data analysis for such activities. These employees work across multiple development programs and, therefore,duration of later-stage clinical trials. As a result, we do not track their costs by program.

21


The table below summarizes ourexpect research and development costs to increase significantly for the foreseeable future as we continue the development of YTX-7739 and YTX-9184 and any product candidates we may develop in the future. We cannot accurately project total program-specific expenses incurred bythrough commercialization. There are numerous factors associated with the successful commercialization of product candidates including future trial design and various regulatory requirements, many of which cannot yet be determined with accuracy based on our stage of development. Additionally, future commercial and regulatory factors beyond our control will impact our clinical development program (in thousands):and plans.

 

 

Three Months Ended March 31,

 

 

 

2020

 

 

2019

 

CF

 

$

3,531

 

 

$

11,855

 

UPR

 

 

2

 

 

 

112

 

Unallocated expenses:

 

 

 

 

 

 

 

 

Employee-related

 

 

2,248

 

 

 

2,813

 

Facility-related

 

 

411

 

 

 

550

 

Other

 

 

326

 

 

 

818

 

Total research and

   development expenses

 

$

6,518

 

 

$

16,148

 

If our ongoing studies and clinical trials areThe successful and if we can raise adequate funding, we expect that our expenses will increase substantially in connection with our ongoing and anticipated clinical trials, preclinical development and commercialization activities.of YTX-7739 and YTX-9184 and any product candidates we may develop in the future is highly uncertain. At this time, we cannot reasonably estimate or know the nature, timing and costs for completingof the clinical development of posenacaftor, dirocaftor, nesolicaftor, or our proprietary combination therapies forefforts that will be necessary to complete the treatment of CF, or the cost associated with thepreclinical and clinical development of any of our other product candidates. The successful development and commercialization of our product candidates is highly uncertain. This is due to the numerous risks and uncertainties associated with product development and commercialization, including the uncertainty of:following:

the timing and progress of preclinical and clinical development activities;

the number and scope progress, outcome,of preclinical and costs of our preclinical development activities, clinical trials, and otherprograms we decide to pursue;

the ability to maintain current research and development activities;programs and to establish new ones;

establishing an appropriate safety profile with IND and registrationIND-enabling or approval-enablingforeign equivalent studies;

successful patient enrollment in, and the initiation and completion of, clinical trials;

the cooperationsuccessful completion of clinical trials with safety, tolerability and approval we receiveefficacy profiles that are satisfactory to the FDA or any comparable foreign regulatory authority;

the receipt of regulatory approvals from third parties including clinical investigators, HIT-CF, CROs, the TDN, and CTN;applicable regulatory authorities;

the timing, receipt and terms of any marketing approvals from applicable regulatory authorities;

our ability to establish new licensing or collaboration arrangements;

the performance of our future collaborators, if any;

establishing commercial manufacturing capabilities or making arrangements with third-party manufacturers;

development and timely delivery of commercial-grade drug formulations that can be used in our planned clinical trials and for commercial launch;

obtaining, maintaining, defending and enforcing patent claims and other intellectual property rights;

significant and changing government regulation;

launching commercial sales of our product candidates, if and when approved, whether alone or in collaboration with others; and

maintaining a continued acceptable safety profile of the product candidates following approval.

Any changes in the outcome of any of these variables or others identified within this filing, with respect to the development of our product candidates in preclinical and clinical development could mean a significant change in the costs and timing associated with the development of these product candidates. For example, if the FDA or another regulatory authority were to delay our planned start of clinical trials or require us to conduct clinical trials or other testing beyond those that we currently expect, or if we experience significant delays in enrollment in any of our planned clinical trials, we could be required to expend significant additional financial resources and time on the completion ofto complete clinical development of that product candidate. We may never obtain regulatory approval for any of our product candidates. Drug commercialization will take several years and millions of dollars in development costs.

General and Administrative Expenses

General and administrative expenses consist primarily of personnel-related expenses, including salaries, benefits, and related benefits, travel, and stock-basedstock/equity-based compensation expenses for personnel in executive, finance, accounting, human resources and other administrative functions. GeneralOther significant general and administrative expenses also include legal fees relating to patent, intellectual property and corporate matters, and fees paid for accounting, audit, consulting and other professional services, as well as facilities, and other allocated expenses, which include direct and allocated expenses for rent, and maintenance of facilities, depreciation, insurance and supplies, as well as professional fees for legal, consulting, accounting, and audit services.other operating costs.

We anticipate that our general and administrative expenses will increase in the future as our business expands to support our continued research activities and development activities, including our future clinical programs. These increases will likely include increased costs related to the hiring of our product candidates.additional personnel and fees to outside consultants, among other expenses. We also anticipate that we will continue to incur increased accounting, audit, legal, patent, regulatory, compliance, director and officer insurance costs, and director expenses, as well as investor and public relations expenses associated with being a public company.company, including costs for audit, legal, regulatory, and tax-related services related to compliance with the rules and regulations of the SEC listing standards applicable to companies listed on a national securities exchange, director and officer insurance premiums and investor relations costs.

22

Other Income (Expense)


Change in Fair Value of Warrant Liabilities

In connection with our loan and security arrangements, we issued warrants to purchase preferred units. These warrants were liability classified and remeasured to fair value at each reporting date, with changes in the fair value recognized as a component of other income (expense) in our statement of operations.

Immediately prior to the Merger, all of our outstanding warrants to purchase preferred units were exchanged and became warrants to purchase shares of common stock. As a result, the fair value of the warrants was reclassified to additional paid-in capital and there is no longer a warrant liability to remeasure.

Interest Expense

Interest expense consists of interest charged on outstanding borrowings associated with our loan and security agreements, as well as amortization of debt issuance costs and accretion of a final payment payable upon the maturity or the repayment in full of all obligations under such loans. Interest expense also consists of interest related to finance leases.

Interest Income and Other Income (Expense), Net

Interest income consists of interest earned on our invested cash equivalents and short-term investments held by us during the reporting periods.

Interest Expense

Interest expense consists of interest paid on our short-term borrowings during the reporting periods.

Other Income (Expense), Net

balances. Other income (expense), net primarily consistsincludes a gain on the extinguishment of debt upon forgiveness of the amortizationPPP loan (see Paycheck Protection Loan section of premiumsthe Description of Indebtedness below).

Income Taxes

Prior to the Yumanity Reorganization, Holdings was treated as a partnership for federal income tax purposes and, discounts on our short-term investmentstherefore, its owners, and the gainsnot Holdings, were subject to U.S. federal or losses associated with the changesstate income taxation. Holdings’ directly held subsidiary was treated as a corporation for U.S. federal income tax purposes and subject to taxation in the fair valuesUnited States. After the Yumanity Reorganization, the Company and its subsidiary are both taxpaying entities. In each reporting period, our tax provision included the effects of consolidating our subsidiary’s results of operations. Since our inception, we have not recorded any income tax benefits for the net losses we incurred in each year or for our earned research and development tax credits, as we believe, based upon the weight of available evidence, that it is more likely than not that all of our derivative liability. The derivative liability relatesnet operating loss carryforwards and tax credits will not be realized. Utilization of U.S. federal and state net operating loss carryforwards and research and development tax credit carryforwards may be subject to a cash settlement option associated withsubstantial annual limitation under Section 382 of the Internal Revenue Code of 1986, and corresponding provisions of state law, due to ownership changes that be occurred previously or that could occur in the future. These ownership changes may limit the amount of carryforwards that can be utilized annually to offset future taxable income. The Company has not conducted a study to assess whether a change of control provision inhas occurred or whether there have been multiple changes of control since inception due to the significant complexity and cost associated with such a study. We have recorded a full valuation allowance against our CFF collaboration agreement. We remeasure the fair value of our derivative liabilitynet deferred tax assets at each reporting period and record the change in fair value in other income (expense), net.balance sheet date.

Critical Accounting Policies and Significant Judgments and Estimates

Our financial statements are prepared in accordance with generally accepted accounting principles in the United States, or GAAP. The preparation of our financial statements and related disclosures requires us to make estimates and judgments that affect the reported amounts of assets, liabilities, revenue, costs and expenses, and the disclosure of contingent assets and liabilities in our financial statements. We base our estimates on historical experience, known trends and events and various other factors that we believe are reasonable under the circumstances, the results of which form the basis for making judgments about the carrying values of assets and liabilities that are not readily apparent from other sources. We evaluate our estimates and assumptions on an ongoing basis. Our actual results may differ from these estimates under different assumptions or conditions.

During the three months ended March 31, 2020, there were no material changes to our critical accounting policies. Our critical accounting policies are described under the heading, “Management’s Discussion and Analysis of Financial Condition and Results of Operations— Critical Accounting Policies and Significant Judgments and Estimates,” in our Annual Report and the notes to the financial statements appearing elsewhere in this Quarterly Report. We believe that of our critical accounting policies, the following accounting policies involve the most judgment and complexity:

revenue recognition;

accrued research and development expenses; and

stock-based compensation.

Accordingly, we believe the policies set forth above are critical to fully understanding and evaluating our financial condition and results of operations. If actual results or events differ materially from the estimates, judgments and assumptions used by us in applying these policies, our reported financial condition and results of operations could be materially affected.

Results of Operations

Comparison of the Three Months Ended March 31, 20202021 and 20192020

The following table summarizes our results of operations for the three months ended March 31, 20202021 and 2019 (in thousands):2020:

 

 

Three Months Ended March 31,

 

 

Increase

 

 

2020

 

 

2019

 

 

(Decrease)

 

  Three Months Ended March 31,     

Revenue

 

$

 

 

$

5,000

 

 

$

(5,000

)

  2021   2020   Change 
  (in thousands) 

Collaboration revenue

  $3,532   $—     $3,532 

Operating expenses:

 

 

 

 

 

 

 

 

 

 

 

 

      

Research and development

 

 

6,518

 

 

 

16,148

 

 

 

(9,630

)

   6,779    5,029    1,750 

General and administrative

 

 

3,587

 

 

 

3,943

 

 

 

(356

)

   6,052    2,032    4,020 
  

 

   

 

   

 

 

Total operating expenses

 

 

10,105

 

 

 

20,091

 

 

 

(9,986

)

   12,831    7,061    5,770 
  

 

   

 

   

 

 

Loss from operations

 

 

(10,105

)

 

 

(15,091

)

 

 

(4,986

)

  $(9,299   (7,061   (2,238

Interest income

 

 

207

 

 

 

357

 

 

 

(150

)

  

 

   

 

   

 

 

Other income (expense):

      

Change in fair value of preferred unit warrant liability

   —      5    (5

Interest expense

 

 

(3

)

 

 

 

 

 

(3

)

   (488   (454   (34

Other income, net

 

 

23

 

 

 

316

 

 

 

(293

)

Interest income and other income (expense), net

   (29   45    (74

Loss on debt extinguishment

   1,134    —      1,134 
  

 

   

 

   

 

 

Total other expense, net

   617    (404   1,021 
  

 

   

 

   

 

 

Net loss

 

$

(9,878

)

 

$

(14,418

)

 

$

(4,540

)

  $(8,682  $(7,465  $(1,217
  

 

   

 

   

 

 

Collaboration Revenue

Collaboration revenue recognized during the three months ended March 31, 2021 of $3.5 million was related to our Collaboration Agreement with Merck. The upfront payment of $15.0 million received in July 2020 was initially recorded as deferred revenue and is being recognized as revenue under the cost-to-cost method as research and development is being performed.

Research and Development Expenses

 

   Three Months Ended March 31,     
   2021   2020   Change 
   (in thousands) 

Direct research and development expenses by program:

      

YTX-7739

  $1,721   $794   $927 

YTX-9184

   503    315    188 

Platform, research and discovery, and unallocated expenses:

       —   

Platform and other early stage research external costs

   1,070    715    355 

Personnel related (including equity-based compensation)

   2,028    2,272    (244

Facility related and other

   1,457    933    524 
  

 

 

   

 

 

   

 

 

 

Total research and development expenses

  $6,779   $5,029   $1,750 
  

 

 

   

 

 

   

 

 

 

23


Revenue

There was no revenueResearch and development expenses were $6.8 million for the three months ended March 31, 2020, as compared to revenue related to the Genentech Agreement2021, an increase of $1.8 million from $5.0 million for the three months ended March 31, 2019.

Research2020. Direct expenses of our YTX-7739 program increased by $0.9 million in the three months ended March 31, 2021, compared to the three months ended March 31, 2020. The change was due primarily to an increase in clinical and Development Expenses

Research and developmentconsultant costs as YTX-7739 progressed from a SAD study in 2020 to MAD clinical studies during the first quarter of 2021. Direct expenses were $6.5of our YTX-9184 program increased by $0.2 million from $0.3 million for the three months ended March 21, 2020 to $0.5 million for the three months ended March 31, 2021. The change was primarily due to preclinical and consulting costs as the program progresses towards clinical studies. Platform and other early-stage research external costs increased by $0.4 million from $0.7 million in the three months ended March 31, 2020 compared to $16.1$1.1 million in the three months ended March 31, 2021. This change was primarily due to decreased laboratory activities as a result of COVID-19 in 2020 as well as preparations for the move to new office and laboratory space in the second quarter of 2020. Personnel related costs decreased by $0.2 million primarily due to employee turnover in the research and development function during 2020 which continued to be reflected in the three months ended March 31, 2021.

General and Administrative Expenses

   Three Months Ended March 31,     
   2021   2020   Change 
   (in thousands) 

Personnel related (including equity-based compensation)

  $2,268   $1,251   $1,017 

Professional and consultant fees

   2,085    649    1,436 

Facility related and other

   1,699    132    1,567 
  

 

 

   

 

 

   

 

 

 

Total general and administrative expenses

  $6,052   $2,032   $4,020 
  

 

 

   

 

 

   

 

 

 

General and administrative expenses were $6.1 million for the three months ended March 31, 2019. The decrease2021, an increase of $9.6$4.0 million was due to a decrease of approximately $8.7 million in clinical-related research activities, $0.6 million in employee-related expenses, $0.2 million in professional fees, and $0.1 million in facility expenses.

General and Administrative Expenses

General and administrative expenses were $3.6from $2.0 million for the three months ended March 31, 2020, compared2020. The increase of $1.0 million in personnel related costs was primarily due to $3.9$0.7 million in stock/equity-based compensation and $0.3 million due to additional hiring in the general and administrative function. Personnel-related costs for each of the three months ended March 31, 2019. The decrease2021 and 2020 included stock/equity-based compensation of $1.0 million and $0.3 million, in generalrespectively. Professional and administrative expenses wasconsultant fees increased by $1.4 million primarily due to higher audit expenses and legal fees related to operating as a decreasepublic company. Facility and other related costs increased by $1.6 million primarily due to incremental public company insurance premiums of $0.7$0.5 million, $0.4 million of lease expense in professional fees, partially offset by an increaseexcess of sublease income, and $0.2 million paid in employee-related expenses, $0.1settlement of litigation.

Other Income (Expense)

Other income (expense), net increased by $1.0 million in facility expenses, and $0.1 million in other expenses.

Interest Income

Interest income was $0.2 million forfrom the three months ended March 31, 2021 to the three months ended March 31, 2020 compared to $0.4resulting primarily from a $1.1 million forgain on the three months ended March 31, 2019. The decreaseextinguishment of $0.2 million in interest earned on cash equivalents and short-term investments is due to a decrease in average balancedebt upon forgiveness of invested cash held during the three months ended March 31, 2020, compared toPPP loan (see Paycheck Protection Loan section of the three months ended March 31, 2019.

Interest Expense

Interest expense was less than $0.1 million for the three months ended March 31, 2020 and consistedDescription of interest paid on short-term borrowings. There was no interest expense for the three months ended March 31, 2019.

Other Income, Net

Other income was less than $0.1 million and $0.3 million for the three months ended March 31, 2020 and 2019, respectively. The decrease of $0.2 million in other income is primarily due to a decrease in net accretion of discounts on short-term securities in the three months ended March 31, 2020 compared to the three months ended March 31, 2019.Indebtedness below).

Liquidity and Capital Resources

Sources of Liquidity

Since our inception, we have not generated revenue from product sales and have incurred significant operating losses. We have generated limited revenue to datelosses and negative cash flows from our collaboration agreements and research grant. We have not yet commercialized any of our product candidates, which are in various phases of preclinical development and clinical trials and we do not expect to generate revenue from sales of any product for several years, if at all.operations. We have funded our operations to date primarily with proceeds received from equity offerings, the issuancesales of convertible promissory notespreferred units and to a lesser extent, paymentsan upfront payment from our collaboration agreement with Merck received in connection with collaboration agreements and a research grant.

As of March 31,July 2020. In December 2020, we hadcompleted the Merger with Proteostasis and acquired its $35.9 million of cash, cash equivalents and short-term investmentsrestricted cash. Immediately following the Merger, we also completed a private placement of an aggregate of 1,460,861 shares of our common stock and received net proceeds of approximately $57.1$31.6 million. As of March 31, 2020, we had an accumulated deficit of $346.5 million. During the three months ended March 31, 2020, we incurred a loss of $9.9 million and used $13.6 million of cash in operations. We expect that our cash, cash equivalents and short-term investments as of March 31, 2020 will enable us to fund our operating expenses and capital requirements, based upon our current operating plan, for at least the next 12 months. We will need additional financing to support our long-term plans for clinical trials, including the MORE trial. Further, while we have limited financial impact to date, it is difficult to assess or predict the future impact of COVID-19, and sustained economic uncertainty could negatively impact our liquidity. Our operation plans may change as a result of many factors, including as a result of COVID and otherwise, and we may need to seek additional funds sooner than planned, through public or private equity or debt financings, third-party funding, marketing and distribution arrangements, as well as other collaborations, strategic alliances and licensing arrangements, or any combination of these approaches.

24


There can be no assurance that we will be able to obtain funding from any of these sources or, if obtained, what the terms of such funding(s) may be, or that any amount that we are able to obtain will be adequate to support our working capital requirements until we achieve profitable operations. We have no current committed sources of additional capital. Although we have been successful in raising capital in the past, there is no assurance that we will be successful in obtaining such additional financing on terms acceptable to us, if at all. The ongoing COVID-19 pandemic is also impacting the global financial marketsfunded operations using borrowings under loan and could impair our ability to raise additional capital when and if needed. If we are unable to obtain funding, we could be forced to delay, reduce or eliminate some or all of our research and development programs, product portfolio expansion or commercialization efforts, which would adversely affect our business prospects, or we may be unable to continue operations.security agreements.

Cash Flows

The following table summarizes our sources and uses of cash for each of the periods presented (in thousands):presented:

 

   Three Months Ended March 31, 
   2021   2020 
   (in thousands) 

Cash used in operating activities

  $(22,288  $(8,283

Cash (used in) provided by investing activities

   (6,275   1,180 

Cash used in financing activities

   (142   (88
  

 

 

   

 

 

 

Net decrease in cash, cash equivalents, and restricted cash

  $(28,705  $(7,191
  

 

 

   

 

 

 

 

 

Three Months Ended March 31,

 

 

 

2020

 

 

2019

 

Cash used in operating activities

 

$

(13,550

)

 

$

(13,429

)

Cash provided by investing activities

 

 

20,768

 

 

 

16,147

 

Cash provided by financing activities

 

 

1,125

 

 

 

56

 

Net increase in cash, cash equivalents and

   restricted cash

 

$

8,343

 

 

$

2,774

 

Net Cash Used in Operating Activities

During the three months ended March 31, 2021, operating activities used $22.3 million of cash, resulting from our net loss of $8.7 million, primarily due to net cash changes in our operating assets and liabilities of $15.6 million and the add back of the $1.1 million gain on extinguishment included in our net loss for the period. Those changes were offset by non-cash charges of $2.9 million, including $1.2 million of non-cash lease expense and $1.4 million of stock/equity-based compensation expense. Net cash usedprovided by changes in our operating assets and liabilities for the three months ended March 31, 2021 consisted of a $3.5 million decrease in deferred revenue due to the recognition of revenue related to the Collaboration Agreement (see note 4 to the financial statements). Additionally, there was a $9.6 million decrease in accounts payable and accrued expenses and other current liabilities, primarily due to $5.7 million that was paid to settle severance and other obligations resulting from the merger, as well as payment of $1.7 million of 2020 performance bonuses offset by 2021 bonus expense accrued, and $1.7 million of banking commissions paid related to the Private Placement that closed in the fourth quarter of 2020. There was also a decrease of $1.1 million in operating activities was $13.6lease liabilities resulting from lease payments, and a $1.5 million duringincrease in prepaid expenses and other current assets, primarily due to the upfront payment of the annual directors’ and officers’ insurance premium.

During the three months ended March 31, 2020, primarily driven byoperating activities used $8.3 million of cash, resulting from our net loss of $9.9$7.5 million and net cash used by changes in our operating assets and liabilities of $4.6,$1.9 million, partially offset by non-cash charges of $0.9$1.1 million. Our net loss was primarily attributed toNet cash used by changes in our research and development activities associated with the advancement of our clinical trials and preclinical studies. Changes in operating assets and liabilities were primarily related to a decrease of $2.1 million in accrued expenses, a decrease of $1.1 million in accounts payable, an increase in prepaid and other current assets of $1.1 million, and a decrease of $0.3 million in operating lease liabilities. Non-cash charges include $0.6 million of stock-based compensation, $0.4 million of depreciation and amortization, partially offset by $0.1 million of accretion of short-term investments.

Net cash used in operating activities was $13.4 million duringfor the three months ended March 31, 2019, primarily driven by our net loss2020 consisted of $14.4a $0.3 million decrease in operating lease liabilities and a $0.1 million increase in prepaid expenses and other current assets, partially offset by non-cash charges of $1.0 million. Our net loss was primarily attributed to our research and development activities associated with the advancement of our preclinical studies and clinical trials. Non-cash charges includea $0.8 million decrease in accounts payable and accrued expenses and other current liabilities.

Changes in accounts payable, accrued expenses and prepaid expenses in all periods were generally due to growth in our business and the timing of stock-based compensation, $0.3vendor invoicing and payments.

Net Cash (Used in)/Provided by Investing Activities

During the three months ended March 31, 2021, net cash used in investing activities was $6.3 million, primarily related to net cash used of depreciation$6.3 million for net purchases of marketable securities and amortization, $0.2 million of stock issued for consulting services, offset by $0.3 millionproceeds from the sales of accretion of short-term investments.

Investing Activitiesassets acquired during the Merger.

During the three months ended March 31, 2020, net cash provided by investing activities was $20.8$1.2 million, consisting of proceeds received fromprimarily related to cash provided by the net sales and maturities of short-term investments of $26.0 million,marketable securities, partially offset by purchasesthe purchase of our short-term investments of $5.2 million.property and equipment.

DuringNet Cash Provided by Financing Activities

Net cash used in financing activities for the three months ended March 31, 2019, net cash provided by investing activities2021 was $16.1$0.1 million, consisting primarily of proceeds received from maturitiespayments of short-term investmentsfinance lease obligations of $37.0 million, partially offset by purchases of short-term investments of $20.8 million and $0.1 millionmillion.

Net cash used in purchases of property and equipment.

Financing Activities

Duringfinancing activities for the three months ended March 31, 2020 net cashwas $0.1 million, consisting primarily of payments of finance lease obligations.

Description of Indebtedness

Loan and Security Agreement

We have outstanding borrowings of $15.0 million (“Tranche 1”), under a loan and security agreement entered into in December 2019 (the “Term Loan”) with Hercules Capital, Inc. (the “Lender”). We may borrow an additional $5.0 million upon the occurrence of a development milestone and an equity event as defined in the agreement (“Tranche 2”), and an additional $10.0 million may become available to be drawn upon lender approval. Borrowings under the Term Loan are repayable in monthly interest-only payments until August 1, 2021, with the option to extend an additional six months upon the drawdown of Tranche 2. The interest-only period will be followed by monthly payments of equal principal plus interest until the loan maturity date of January 1, 2024. Outstanding borrowings bear interest at the greater of (i) 8.75% and (ii) the prime rate as reported in the Wall Street Journal plus 4.00%. A final payment fee of 5.25% of the amounts drawn under the Term Loan is due upon the earlier of the maturity date or the repayment date if paid early, whether voluntary or upon acceleration due to default. We may repay the Term Loan at any time by paying the outstanding principal balance in full, along with any unpaid accrued interest, the final payment fees of 5.25% of the amounts drawn and a prepayment fee calculated on amounts being prepaid. The prepayment fee is 3.0% if the Term Loan is repaid within the one-year anniversary of the draw date, 2.0% if paid between the first and second-year anniversary of the draw date and 1.0% if paid after the second anniversary of the draw date but before the maturity date.

In April 2020, the Term Loan was amended to permit indebtedness consisting of a loan under the PPP of the Coronavirus Aid, Relief, and Economic Security Act (the “CARES Act”), provided that such loan shall be unsecured, shall not contain any terms or conditions that are adverse to the lender’s rights under the loan and that we will not prepay such loan. In June 2020, the Term Loan was amended and an additional final payment fee of $0.3 million became due upon repayment of the loan.

On December 22, 2020, we entered into an Unconditional Secured Guaranty and Pledge Agreement (the “Guaranty”) with the Lender as a condition to the Lender’s consent to the Merger under the Term Loan between us as borrower and the Lender. Immediately prior to the Merger, we entered into a Fourth Amendment and Consent to Loan and Security Agreement dated as of December 22, 2020 with the Lender (the “Loan Amendment”). The Guaranty provides for our guaranty of our obligations under the Loan Agreement and provides the Lender a security interest in all of our assets other than intellectual property as collateral. The Loan Amendment provides for the Lender’s consent to the Merger and to the creation and funding of a Silicon Valley Bank Paycheck Protection Program escrow account to hold funds in connection with our outstanding Paycheck Protection Program loan amounts for which we have submitted a forgiveness application. The Loan Amendment also amends the definition of “Change in Control” to include the situations in which we no longer control Yumanity, Inc., our wholly-owned subsidiary. The remaining terms and conditions of the Loan Agreement generally continue in the form existing prior to the Loan Amendment.

On March 29, 2021, the Term Loan was amended again to allow for the creation of a new foreign subsidiary, as well as changing certain covenants related to the financial operations of said subsidiary. The subsidiary was formed on April 23, 2021.

On April 13, 2021, the Term Loan was amended to reduce the end-of-term charge from $0.3 million to $0.1 million and to extend the availability of Tranche 2 from March 31, 2021 to June 30, 2021.

Borrowings under the Term Loan are collateralized by financingsubstantially all of our personal property, other than our intellectual property. There were no financial covenants associated with the Term Loan; however, we are subject to certain affirmative and negative covenants restricting our activities, wasincluding limitations on dispositions, mergers or acquisitions; encumbering our intellectual property; incurring indebtedness or liens; paying dividends; making certain investments; and engaging in certain other business transactions. The obligations under the Term Loan are subject to acceleration upon the occurrence of specified events of default, including a material adverse change to our business, operations or financial or other condition. Upon the occurrence of an event of default and until such event of default is no longer continuing, the annual interest rate will be 5.0% above the otherwise applicable rate.

Paycheck Protection Program Loan

In April 2020, prior to entering into the Merger Agreement with Proteostasis in August 2020, we issued a Promissory Note to Silicon Valley Bank, pursuant to which we received loan proceeds of $1.1 million primarily related(the “PPP Loan”), provided under the PPP established under the CARES Act and guaranteed by the U.S. Small Business Administration. The PPP Loan was unsecured, was scheduled to mature on April 24, 2022, and had a fixed interest rate of 1.0% per annum. Equal monthly payments of principal and interest will be due commencing in August 2021 until the maturity date. Interest accrues on the unpaid principal balance from the inception date of the loan. Forgiveness of the PPP Loan is only available for principal that is used for the limited purposes that expressly qualify for forgiveness under U.S. Small Business Administration requirements. On April 3, 2021, we were notified by Silicon Valley Bank that our forgiveness application was accepted by the Small Business Association as of March 30, 2021. Accordingly, we have recognized $1.1 million in income for debt extinguishment.

At-the-Market Offering Program

In April 2021, the Company entered into a sales agreement with Jefferies LLC (“Jefferies”) with respect to an at-the-market (“ATM”) offering program under which the Company may issue and sell, from time-to-time at its sole discretion, shares of its common stock, in an aggregate offering amount of up to $60.0 million. Jefferies acts as the Company’s sales agent and will use commercially reasonable efforts to sell shares of common stock from time-to-time, based upon instruction from the Company.The Company will pay Jefferies up to 3% of the gross proceeds from any common stock sold through the issuancesales agreement. The Company did not sell any shares of short-term borrowings of $1.2 million, offset by payments made on short-term borrowings of $0.1 million.

Duringits common stock under the ATM program during the three months ended March 31, 2019, net cash provided by financing activities was less than $0.1 million, primarily resulting from the issuance of common stock pursuant to our employee stock purchase plan and stock option exercises.2021.

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Future Funding Requirements

Our primary uses of capital are, and we expect will continue to be, compensation and related expenses, third-party clinical research and development services, clinical costs, legal and other regulatory expenses and general overhead costs. We have based our estimates on assumptions that may prove to be incorrect, and we could use our capital resources sooner than we currently expect. Additionally, the process of testing product candidates in clinical trials is costly, and the timing of progress in these trials is uncertain. We cannot estimate the actual amounts necessary to successfully complete the development and commercialization of our product candidates or whether, or when, we may achieve profitability. We expect our expenses to increase substantially in connection with our ongoing activities, particularly as we advance the preclinical activities and clinical trials of our product candidates in development. In addition, we expect to incur additional costs associated with operating as a public company. We believe that our existing cash, cash equivalents and short-term investments will enable us to fund our operating expenses and capital expenditure requirements into the third quarter of 2022 from the date of issuance of the condensed consolidated financial statements included in this quarterly report. The timing and amount of our operating expenditures will depend largely on:

Our expenses will also increase as we:

the scope, number, initiation, progress, timing, costs, design, duration, any potential delays and results of clinical trials and nonclinical studies for our current or future product candidates;

continue to pursue the clinical development of our most advanced product candidates, including posenacaftor, dirocaftor and nesolicaftor, as well as our combination therapies;

seek support and approval from our collaboration partners, the TDN, HIT-CF, CTN, and other interested parties;

continue the research and development of our otherplans we establish for these product candidates;

seek to identifythe number and develop additional product candidates;

seek marketing approvals for anycharacteristics of our product candidates that successfully complete clinical development;

develop and expand our sales, marketing, and distribution capabilities for our product candidates for which we obtain marketing approval;

scale up our manufacturing processes and capabilities to support our ongoing preclinical activities, clinical trials of our product candidates and commercialization of any of our product candidates for whichprograms that we obtain marketing approval;develop or may in-license;

maintain, expand, and protect our intellectual property portfolio;

expand our operational, financial, and management systems, and increase personnel, including personnel to support our clinical development, manufacturing, and commercialization efforts, and our operations as a public company; and

increase our product liability and clinical trial insurance coverage as we initiate additional clinical trials, expand our existing clinical trials, and launch commercialization efforts.

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Because of the numerous risks and uncertainties associated with research, development, and commercialization of pharmaceutical drugs, we are unable to estimate the exact amount of our working capital requirements. Our future funding requirements will depend on many factors, including:

the scope, initiation, progress, results, and costs of researching and developing our product candidates, and conducting preclinical studies and clinical trials;

the outcome, timing and cost of and the costs involved in, obtaining regulatory reviews, approvals for any of our product candidates fromor other actions to meet regulatory requirements established by the FDA EC and comparable foreign regulatory authorities, including the potential for suchthe FDA or comparable foreign regulatory authorities to require that we perform more trialsstudies for our product candidates than those that we currently expect;

market acceptanceour ability to obtain marketing approval for our product candidates;

the cost of filing, prosecuting, defending and enforcing our patent claims and other intellectual property rights covering our product candidates;

our ability to maintain, expand and defend the scope of our drugintellectual property portfolio, including the cost of defending intellectual property disputes, including patent infringement actions brought by third parties against us or our product candidates;

the cost and timing of completion of commercial-scale outsourced manufacturing activities with respect to our product candidates;

our ability to establish and costs involved in, manufacturing our drug candidatesmaintain licensing, collaboration or similar arrangements on favorable terms and whether and to what extent we retain development or commercialization responsibilities under any drugs we successfully commercialize;new licensing, collaboration or similar arrangement;

the cost of establishing sales, marketing and distribution capabilities for our drugany product candidates if either candidate receivesfor which we may receive regulatory approval andin regions where we determinechoose to commercialize it ourselves;our products on our own;

the success of any other business, product or technology that we acquire or in which we invest;

the costs of acquiring, licensing or investing in additional businesses, products, product candidates and technologies;

our need and ability to establishhire additional management and maintain strategic collaborations, licensing or other arrangements,scientific and the financial terms of such agreements;medical personnel;

delays that may be caused by changing regulatory requirements;

diversion of healthcare resources away from the conduct of clinical trials as a result of the ongoing COVID-19 pandemic, including the diversion of hospitals serving as our clinical trial sites and hospital staff supporting the conduct of our clinical trials;

the interruption of key clinical trial activities, such as clinical trial site monitoring, due to limitations on travel, quarantines or social distancing protocols imposed or recommended by federal or state governments, employers and others in connection with the ongoing COVID-19 pandemic;

cost and timing of hiring new employees to support our continued growth;

the costs involvedto operate as a public company in preparing, filing, prosecuting, maintaining, defending,the U.S. including the need to implement additional financial and enforcing patent claims, including litigation costsreporting systems and the outcomeother internal systems and infrastructure for our business;

market acceptance of such litigation; and

the timing, amount and receipt of sales of, or milestone payments related to or royalties on, our current or future product candidates, if any.

We have no productsto the extent any are approved for commercial salesale; and

the effect of competing technological and market developments.

The Merger and a concurrent private placement were completed in December 2020, which provided us with $35.1 million incremental cash from the Merger and net proceeds of $31.6 million from the concurrent private placement. As of May 13, 2021, the issuance date of the condensed consolidated financial statements for the three months ended March 31, 2021, we expect that our existing cash, cash equivalents and marketable securities will fund our operating expenses, capital expenditure requirements and debt service payments into the third quarter of 2022. We have not generated any product revenues from product salesbased this estimate on assumptions that may prove to date. be wrong, and we could exhaust our available capital resources sooner than we expect.

Until such time, if ever, as we can generate substantial product revenue, sufficient to achieve profitability, we expect to finance our cash needs through a combination of equity offerings, debt financings, collaboration agreements, other third-party funding, strategic alliances,collaborations, and marketing, distribution or licensing arrangements or marketing and distribution arrangements. The COVID-19 pandemic continues to rapidly evolve and has already resulted in a significant disruption of global financial markets. If the disruption persists and deepens, we could experience an inability to access additional capital, which could in the future negatively affect our operations.with third parties. To the extent that we raise additional capital through the sale of equity or convertible debt securities, the ownership interest willof our stockholders may be materially diluted, and the terms of thesesuch securities maycould include liquidation or other preferences that adversely affect the rights of a common stockholder.our stockholders. Debt financing and preferred equity financing, if available, may involve agreements that include restrictive covenants limiting or restrictingthat limit our ability to take specificspecified actions, such as incurring additional debt, making capital expenditures or declaring dividends. If we raise additional funds through other third-party funding, collaborations agreements, strategic alliances,or marketing, distribution or licensing arrangements or marketing and distribution arrangements,with third parties, we may have to relinquish valuable rights to our technologies, future revenue streams, research programs or product candidates or grant licenses on terms that may not be favorable to us. If we are unable to raise additional funds through equity or debt financings or other arrangements when needed, we may be required to delay, limit, reduce or terminate our product development or future commercialization efforts.

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Based upon our current operating plan, we believe our existing cash, cash equivalents and short-term investments will enable us to fund our operating expenses and capital expenditure requirements, for at least 12 months from the date that these financial statements are issued. However, additional funding will be necessary to fund our MORE trial and to advance our proprietary combination therapy candidates through regulatory approval and into commercialization, if approved. We intend to obtain additional funding through public or private financing or collaborative arrangements with strategic partners to increase the funds available to support our operating and capital needs. Although we have been successful in raising capital in the past, there is no assurance that we will be successful in obtaining additional financing on terms acceptable to us, if at all, nor is it considered probable under the accounting standards. If we are unable to raise additional funds through equity or debt financings when needed, we may be required to delay, limit, reduce or terminateeliminate our product development or future commercialization efforts, or grant rights to develop and market product candidates that we would otherwise prefer to develop and market ourselves.

Recently Issued and Adopted Accounting Pronouncements

A description of recently issued accounting pronouncements that may potentially impact our financial position and results of operations is disclosed in Note 2 to our condensed consolidated financial statements included in this Quarterly Report on Form 10-Q.

Contractual Obligations and Commitments

Under various agreements, we will be required to make milestone payments and pay royalties and other amounts to third parties.

We enter into contracts in the normal course of business with CROs for clinical trials, preclinical research studies, testing and other services, and products for operating purposes. These contracts generally provide for termination upon notice, and therefore we believe that our non-cancelable obligations under these agreements are not material.

JOBS Act

In April 2012, the Jumpstart Our Business Startups Act of 2012, or the JOBS Act, was enacted. Section 107 of the JOBS Act provides that an emerging growth company can take advantage of an extended transition period for complying with new or revised accounting standards. Thus, an emerging growth company can delay the adoption of certain accounting standards until those standards would otherwise apply to private companies. We have irrevocably elected not to avail ourselves of this extended transition period and, as a result, we will adopt new or revised accounting standards on the relevant dates on which adoption of such standards is required for other public companies.

Off-Balance Sheet Arrangements

We did not have during the periods presented, and we do not currently have, any off-balance sheet arrangements, as defined in the rules and regulations of the SEC.

Item 3. Quantitative and Qualitative Disclosures About Market Risk.

Quantitative and Qualitative Disclosures About Market Risk

We are a smaller reporting company, as defined by in Rule 12b-2 ofunder the Securities Exchange Act of 1934, as amended, for this reporting period and are not required to provide the information required under this item.

Item 4. Controls and Procedures.

Item  4.

Management’s Evaluation of our Disclosure Controls and Procedures.

Management’s Evaluation of our Disclosure Controls and Procedures

We maintainOur management, with the participation of our President and Chief Executive Officer and our Chief Business Officer (our principal executive officer and principal financial officer, respectively), evaluated the effectiveness of our disclosure controls and procedures as of March 31, 2021. The term “disclosure controls and procedures,” as defined in Rules 13a-15(e) and 15d-15(e) under the Exchange Act, means controls and other procedures of a company that are designed to ensure that information required to be disclosed by a company in the reports that we fileit files or submitsubmits under the Securities and Exchange Act of 1934 is (1) recorded, processed, summarized and reported within the time periods specified in the SEC’s rules and formsforms. Disclosure controls and (2)procedures include, without limitation, controls and procedures designed to ensure that information required to be disclosed by a company in the reports that it files or submits under the Exchange Act is accumulated and communicated to ourthe company’s management, including our President and Chief Executive Officer, who is ourits principal executive officer and our interim principal financial officer, and our Head of Finance, who is our principal accounting officer,officers, as appropriate to allow timely decisions regarding required disclosure.

As of March 31, 2020, our management, with the participation of our principal executive officer, who is also our interim principal financial officer, and our principal accounting officer, evaluated the effectiveness of our disclosure controls and procedures (as defined in Rules 13a-15(e) and 15d-15(e) under the Securities Exchange Act of 1934). Our management Management recognizes that any controls and procedures, no matter how well designed and operated, can provide only reasonable assurance of achieving their objectives and management necessarily applies its judgment in evaluating the cost-benefit relationship of possible controls and procedures. Our principal executive officer, who is also our interim principal financial officer, and our principal accounting officer, have concluded based uponBased on the evaluation described above that,of our disclosure controls and procedures as of March 31, 2020,2021, our President and Chief Executive Officer and our Chief Business Officer concluded that, as of such date, our disclosure controls and procedures were effective at the reasonable assurance level.

Changes in Internal Control over Financial Reporting

There were no changesNo change in our internal control over financial reporting (as defined in Rules 13a-15(f) and 15d-15(f) under the Exchange Act) occurred during the three months ended March 31, 20202021 that havehas materially affected, or areis reasonably likely to materially affect, our internal control over financial reporting.

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PART II — OTHERII—OTHER INFORMATION

Item  1.

Legal Proceedings

InItem 1. Legal Proceedings.

From time to time, we may be subject to legal proceedings and claims in the ordinary course of business, we are from timebusiness. Information with respect to time involved in lawsuits, claims, investigations, proceedings, and threats of litigation relating to intellectual property, commercial arrangements, employment and other matters. While the outcome of these proceedings and claims cannot be predicted with certainty, as of March 31, 2020, we were not party to any material pending legal proceedings and we are not awarethis item is included in Note 10 of any claims or actions pending or threatened against us that would have a material adverse impactour condensed consolidated financial statements contained in Part II, Item 8 of this Quarterly Report on our financial position, results of operations or cash flows.Form 10-Q, which is incorporated herein by reference.

Item 1A. Risk Factors.

Item  1A.

Risk Factors

Investing in our common stock involves a high degree of risk. You should carefully consider the following risks and uncertainties, together with all of the other information in this Quarterly Report on Form 10-Q, or this report, including our condensed consolidated financial statements and related notes and “Management’s Discussion and Analysis of Financial Condition and Results of Operations,” as well as our other filings with the Securities and Exchange Commission (“SEC”), before investing in our common stock. Any of the risksrisk factors we describe below could adversely affect our business, financial condition or results of operations. The market price of our common stock could decline if one or more of these risks or uncertainties actuallywere to occur, causingwhich may cause you to lose all or part of your investment. The impact of COVID-19 may also exacerbate other risks discussed in this filing, any of which could have a material effect on us. This situation is changing rapidly and additional impacts may arise.the money you paid to buy our common stock. Additional risks that weare currently do not know about,unknown to us or that we currently believe to be immaterial may also impair our business. Certain statements below are forward-looking statements. See “Forward-Looking“Cautionary Note Regarding Forward-Looking Statements” in this report.Quarterly Report on Form 10-Q.

Risks Related to Our Business, Financial Position, and IndustryNeed for Additional Capital

We are a clinical stage biopharmaceutical company with a very limited operating history and no products approved for commercial sale, which may make it difficult to evaluate our current business and predict our future success and viability.

We are a clinical stage biopharmaceutical company with a limited operating history, focused on developing therapeutics for neurodegenerative diseases. We were initially formed as a limited liability company in 2014 and converted into a corporation in 2015, we have no products approved for commercial sale, and we have not generated any revenue from product sales to date. We began human clinical trials for YTX-7739 at the planning stagesend of 2019 and have not initiated clinical trials for a Phase 3 clinical trialany of our triple combination of posenacaftor, dirocaftor,other current product candidates. Our operations to date have been limited primarily to organizing and nesolicaftor in patients with the most common F508del mutationstaffing, raising capital, and if such trial fails to demonstrate safetyconducting research and efficacy to the satisfaction of regulatory authorities or does not otherwise produce positive results, we may incur additional costs or experience delays in completing, or ultimately be unable to complete, the development and commercialization ofactivities for our lead product candidates.

Before obtainingTo date, we have not initiated or completed a pivotal clinical trial, obtained marketing approval from regulatory authorities for the saleany product candidates, manufactured a commercial scale product, or arranged for a third party to do so on our behalf, or conducted sales and marketing activities necessary for successful product commercialization. Our short operating history as a company makes any assessment of our proprietary triple combination product candidates, we or a potential collaborator must conduct extensive trialsfuture success and viability subject to demonstrate the safety and efficacy of our proprietary triple combination in humans.significant uncertainty. We will encounter risks and difficulties frequently experienced by early-stage biopharmaceutical companies in rapidly evolving fields, and we have not be ableyet demonstrated an ability to submit an NDA or MAA unlesssuccessfully overcome such risks and until we receive data demonstrating that a pivotal trial has achieved its primary endpoints.

Despite the results reported in our Phase 2 clinical trials,difficulties. If we do not know whether a potential Phase 3 clinical trialaddress these risks and difficulties successfully, our business will demonstrate adequate efficacy and safety to result in regulatory approval to market our proprietary triple combination to address the treatment of rare CFTR mutations in any particular jurisdiction.suffer.

Clinical testing is expensive and difficult to design and implement, can take many years to complete and is inherently uncertain as to the outcome. A failure of one or more trials can occur at any stage of testing. The outcome of preclinical studies and early clinical trials may not accurately predict the success of later trials, and interim results of a trial do not necessarily predict final results. A number of companies in the pharmaceutical and biotechnology industries have suffered significant setbacks in advanced trials due to lack of efficacy or unacceptable safety profiles, notwithstanding promising results in earlier trials.

We have incurred significant operating losses since our inception. Weinception and anticipate that we will continue to incur significantcontinued losses for the foreseeable future, and we may never achieve or maintain profitability.future.

We are a drug researchhave funded our operations to date through proceeds from collaborations and development company focused primarily on developingsales of preferred units. From our lead product candidates, PTI-801 or posenacaftor, PTI-808 or dirocaftorinception through March 31, 2021, we have received gross proceeds of $125.5 million from such transactions. As of March 31, 2021, our cash, cash equivalents and PTI-428 or nesolicaftor for the treatment of CF as part of our proprietary combination therapy candidates.marketable securities were $62.9 million. We have incurred significant net losses in each year since our inception, including net losses of $9.9 million and $14.4 million for the three months ended March 31, 2020 and 2019, respectively. As of March 31, 2020, we hadhave an accumulated deficit of $346.5 million.$156.5 million as of March 31, 2021.

29Substantially all of our operating losses have resulted from costs incurred in connection with general and administrative costs associated with our operations, and our research and development programs, including for our preclinical and clinical product candidates and our discovery engine platform. We expect to incur increasing levels of operating losses over the next several years and for the foreseeable future. Our prior losses, combined with expected future losses, have had and will continue to have an adverse effect on our stockholders’ deficit and working capital. In any particular quarter or quarters, our operating results could be below the expectations of securities analysts or investors, which could cause our stock price to decline.


We expect our research and development expenses to significantly increase in connection with our clinical trials of our product candidates. In addition, if we obtain marketing approval for our product candidates, we will incur significant sales and marketing, legal, and outsourced-manufacturing expenses. As a public company, we expect to continue to incur significant and increasing operating losses for the foreseeable future. Because of the numerous risks and uncertainties associated with developing pharmaceutical products, we are also unable to predict the extent of any future losses or when we will become profitable, if at all. Even if we do become profitable, we may not be able to sustain or increase our profitability on a quarterly or annual basis.

Drug development is a highly uncertain undertaking and involves a substantial degree of risk. We have never generated any revenue from product sales, and we may never generate revenue or be profitable.

Our ability to become profitable depends upon the ability of our product candidates to generate revenue. To date, we have financednot generated any revenue from our operations primarily throughproduct candidates and we do not know when, or if, we will do so. We do not anticipate generating any revenue from product sales until after we have successfully completed clinical development and received regulatory approval for the commercial sale of equity securities and debt financings. We have devoted mosta product candidate, if ever. Our ability to generate revenue depends on a number of our financial resources to research and development,factors, including, ourbut not limited to:

successfully completing preclinical and clinical development activities. We have not completedof our product candidates;

successfully submitting investigational new drug, or IND, applications or comparable applications, for our product candidates;

identifying, assessing, and/or developing new product candidates from our discovery engine platform;

developing a sustainable and scalable manufacturing process for our product candidates, as well as establishing and maintaining commercially viable supply relationships with third parties that can provide adequate products and services to support clinical activities and commercial demand for our product candidates;

the prevalence, duration and severity of potential side effects or other safety issues experienced with our product candidates or future product candidates, if any;

negotiating favorable terms in any collaboration, licensing, or other arrangements into which we may enter;

obtaining regulatory approvals for product candidates for which we successfully complete clinical development;

launching and successfully commercializing product candidates for which we obtain regulatory approval, either by establishing a sales, marketing, and distribution infrastructure or collaborating with a partner;

negotiating and maintaining an adequate price for our product candidates, both in the United States and in foreign countries where our products are commercialized;

obtaining market acceptance of our product candidates as viable treatment options;

building out new facilities or expanding existing facilities to support our ongoing development activity;

addressing any competing technological and market developments;

maintaining, protecting, expanding, and enforcing our portfolio of intellectual property rights, including patents, trade secrets, and know-how; and

attracting, hiring, and retaining qualified personnel.

Because of the numerous risks and uncertainties associated with drug development, we are unable to predict the timing or amount of our expenses, or when we will be able to generate any meaningful revenue or achieve or maintain profitability, if ever. In addition, our expenses could increase beyond our current expectations if we are required by the U.S. Food and Drug Administration (the “FDA”), or foreign regulatory agencies, to perform studies in addition to those that we currently anticipate, or if there are any delays in any of our current or future collaborators’ clinical trials or the development of any of our product candidates. We expectEven if one or more of our product candidates is approved for commercial sale, absent our entering into a collaboration or partnership agreement, we anticipate incurring significant costs associated with commercializing any approved product candidate and ongoing compliance efforts.

Even if we are able to generate revenue from the sale of any approved products, we may not become profitable and may need to obtain additional funding to continue to incur significant and increasing losses and negative cash flowsoperations. Revenue from the sale of any product candidate for which regulatory approval is obtained will be dependent, in part, upon the foreseeable future. The size of our losses will depend,the markets in part, on the rate of future expenditures and our ability to generate revenues. In particular, we expect to incur substantial and increased expenses as we:

continue the clinical development of our lead product candidates, posenacaftor, dirocaftor and nesolicaftor, including, without limitation, as part of our proprietary combination therapy candidates, for the treatment of CF;

seek to obtain regulatory approvals for our proprietary combination therapy candidates, and our other product candidates;

seek cooperation and support from third parties, including clinical investigators, industry experts, therapeutic development networks of patient advocacy groups and clinical research organizations, as we enroll patients in our clinical trials;

conduct our ongoing clinical trials and prepare for additional clinical trials and potential commercialization potential combination therapies, and our other product candidates;

scale up contracted manufacturing processes and quantities to conduct our ongoing clinical trials and prepare for additional clinical trials and the commercialization of potential combination therapies, and our other product candidates for any indicationsterritories for which we receivegain regulatory approval;

establish outsourcing ofapproval, the accepted price for the product, the ability to get reimbursement at any price, and whether we own the commercial manufacturingrights for that territory. The precise number of posenacaftor, dirocaftorpeople with Parkinson’s disease, Alzheimer’s disease, and nesolicaftor andamyotrophic lateral sclerosis (“ALS”) is unknown. Our projections of both the number of people who have these diseases, as well as the subset of people with these diseases who have the potential to benefit from treatment with our other product candidates, are based on estimates. If the number of addressable patients is not as significant as we anticipate, the indication approved by regulatory authorities is narrower than we expect, or the reasonably accepted population for any indications for whichtreatment is narrowed by competition, physician choice, or treatment guidelines, we may receive regulatory approval;

establish an infrastructure for thenot generate significant revenue from sales marketing and distribution of potential combination therapies, and our other product candidates, for any indications for which we may receive regulatory approval;

continue to advance our combination therapies as potential treatments for CF in clinical trials;

prepare for Phase 3 trials, including, without limitation, trial design, conducting additional preclinical or nonclinical studies, manufacturing Phase 3 drug substance and drug product, analyzing Phase 2 data and other necessary work to support commencement of Phase 3 trials;

expand our research and development activities and advance the discovery and development programs for other product candidates, including, without limitation, preclinical laboratory, animal and other testing and reports and the preparation of investigational new drug filings in the United States, and the equivalent in non-U.S. jurisdictions where we may seek to conduct clinical trials;

maintain, expand and protect our intellectual property portfolio;

continue our research and development efforts and seek to discover additional product candidates, including back-up candidates to existing product candidates; and

add clinical, regulatory, operational, financial and management information systems to support our clinical development and commercialization efforts and operations as a public company.

We do not have any drugs that have received regulatory approval. Our business is dependent on our ability to successfully complete preclinical and clinical development of, obtain regulatory approval for, and,even if approved, successfully commercialize our current and future drug candidates in a timely manner. An inability to effectively commercialize our current and future product candidates and to maximize their potential where possible through successful research and development activities, whether due to the impacts of the ongoing COVID-19 pandemic or otherwise, could have an adverse effect on our business, financial condition, results of operations and growth prospects.

approved. Even if we do achieve profitability, we may not be able to sustain or increase profitability on a quarterly or annual basis.

Our failure to become and remain profitable would depress thedecrease our value of our company and could impair our ability to raise capital, expand our business, maintain our research and development efforts, diversify our pipeline of product offeringscandidates, or continue our operations. Aoperations and cause a decline in the value of our company could cause you to losecommon stock, all or partany of your investment.which may adversely affect our viability.

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Our abilityDue to generate future revenues from product sales is uncertainthe significant resources required for the development of our programs, and depends upondepending on our ability to successfully develop, obtain regulatory approval for and commercialize our product candidates, as well as the receipt and/or maintenance of regulatory approval of products and product candidates under development by third parties.

Our ability to generate revenue and achieve profitability depends on our ability, alone or with collaborators, to successfully complete theaccess capital, we must prioritize development of obtain the necessary regulatory approvals for, and commercialize, acertain product candidate or candidates. Our several development programs are currently focused on demonstrating their respective clinical benefit for CF patients. We do not anticipate generating revenues from sales of our proprietary combination therapy candidates, or any other product candidate for the foreseeable future, if ever. Our ability to generate future revenues from product sales depends heavily on:

Vertex’s continued compliance with regulatory requirements, the continued commercial availability of ivacaftor and lumacaftor, and ivacaftor and tezacaftor, with or without elexacaftor, the reimbursement of their cost to CF patients by insurers and their overall success in the market;

obtaining favorable results for and advancing the development of posenacaftor, dirocaftor, nesolicaftor, our proprietary combination therapy candidates, and our other product candidates, including successfully enrolling patients in and completing our ongoing clinical trials and initiating and completing additional clinical trials;

obtaining regulatory approval in the United States of our proprietary combination therapy candidates, and our other product candidates for CF and equivalent foreign regulatory approvals;

launching and commercializing our proprietary combination therapy candidates, and our other product candidates, including building a production infrastructure and a sales force, and collaborating with third parties;

achieving broad market acceptance of our proprietary combination therapy candidates, and our other product candidates in the medical community and with third-party payors; and

generating and advancing through clinical development, a pipeline of product candidates in addition to posenacaftor, dirocaftor, nesolicaftor, our proprietary combination therapy candidates, and next-generation CFTR modulators.

Conducting preclinical testing and clinical trials is a time-consuming, expensive and uncertain process that takes years to complete, andMoreover, we may never generate the data necessaryfail to obtain regulatory approval and achieve product sales. Our anticipated development costs would likely increase if we do not obtain favorable results or if development of any product candidate is delayed. An inability to effectively commercializeexpend our current and future drug candidates and to maximize their potential where possible through successful research and development activities, whether due to the impacts of the ongoing COVID-19 pandemic or otherwise, could have an adverse effectlimited resources on our business, financial condition, results of operations and growth prospects.

Further, activities associated with the development and commercialization of our current and future drug candidates are subject to comprehensive regulation by the U.S. Food and Drug Administration, or FDA, and other regulatory agencies in the United States and similar regulatory authorities outside the United States. In particular, if we are required by the FDA and comparable regulatory authorities in other countries to perform studies or trials in addition to those that we currently expect to undertake, we would likely incur higher costs and it will likely take more time than we anticipate. Because of the numerous risks and uncertainties associated with pharmaceutical product development, we are unable to predict the timing or amount of any increase in our anticipated development costs. Failure to obtain regulatory approval in the United States or other jurisdictions would prevent us from commercializing and marketing our current and future drug candidates.

Even if we obtain approval from the FDA and comparable foreign regulatory authorities for our current and future drug candidates, any approval might contain significant limitations related to use restrictions for specified age groups, warnings, precautions or contraindications, or may be subject to burdensome post-approval study or risk management requirements. If we are unable to obtain regulatory approval, or any approval contains significant limitations, we may not be able to obtain sufficient funding or generate sufficient revenue to continue the development of that drug candidate or any other drug candidate that we may in-license, develop or acquire in the future.

Furthermore, even if we obtain regulatory approval for our current and future drug candidates, we will still need to develop a commercial organization, establish a commercially viable pricing structure and obtain approval for adequate reimbursement from third-party and government payors. If we are unable to successfully commercialize our current and future drug candidates, we may not be able to generate sufficient revenue to continue our business. As a result, we cannot assure you that we will be able to generate revenues from sales of any approved product candidates or indications that we will achievemay be more profitable or for which there is a greater likelihood of success.

Our current portfolio consists of two programs and two additional potential programs. Our lead product candidate, YTX-7739, is in Phase 1 clinical development. We seek to maintain profitability even if we do generate sales.

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We will require additional capitala process of prioritization and resource allocation to fund our operations. If we fail to obtain additional capital, we will be forced to delay, reduce or eliminate one or moremaintain an optimal balance between aggressively advancing product candidates, such as YTX-7739, and ensuring replenishment of our product research and development programs, seek corporate partnersportfolio.

Due to the significant resources required for the development of our product candidates, we must focus on specific diseases and disease pathways and decide which product candidates to pursue and advance and the amount of resources to allocate to each. Our decisions concerning the allocation of research, development, programscollaboration, management, and financial resources toward particular product candidates or therapeutic areas may not lead to the development of any viable commercial product and may divert resources away from better opportunities. If we make incorrect determinations regarding the viability or market potential of any of our product candidates or misread trends in the biopharmaceutical industry, in particular for neurodegenerative diseases, our business, financial condition, and results of operations could be materially adversely affected. As a result, we may fail to capitalize on viable commercial products or profitable market opportunities, be required to forego or delay pursuit of opportunities with other product candidates or other diseases and disease pathways that may later prove to have greater commercial potential than those we choose to pursue, or relinquish or license on unfavorable terms ourvaluable rights to technologiessuch product candidates through collaboration, licensing, or other royalty arrangements in cases in which it would have been advantageous for us to invest additional resources to retain sole development and commercialization rights.

We will need additional funding to advance YTX-7739 through clinical development, which funding may not be available on acceptable terms, or at all. Failure to obtain this necessary capital when needed may force us to delay, limit, or terminate our product candidates.development efforts or other operations.

Developing pharmaceutical products, including conducting preclinical studiesAs of March 31, 2021, our cash, cash equivalents and marketable securities were $62.9 million. We will require additional funding to advance YTX-7739 beyond Phase 1 clinical trials and other planned early development of other programs generated by our discovery engine platform. Our ability to secure this additional funding may be adversely impacted by negative or ambiguous results in our Phase 1 clinical trial for YTX-7739. Developing small-molecule products is a time-consuming, expensive, and uncertain process that takes years to complete. Wewe expect our discovery, research, and development expenses to increase substantially increase in connection with our ongoing activities, particularly as we advance our product candidates in clinical programstrials. We may also need additional funds sooner if we choose to pursue additional indications and/or geographies for posenacaftor, dirocaftor, nesolicaftor, which are our proprietary combination therapyproduct candidates and asor otherwise expand more rapidly than we develop any other current or future product candidates.presently anticipate.

Based uponIn addition, our current operating plan, we believe thatindependent registered public accounting firm has included an emphasis of matter paragraph relating to our existing cash, cash equivalents and short-term investments of $57.1 million as of March 31, 2020 will enable usneed for additional financing to fund operations in its report on our operating expenses and capital expenditure requirements for at least 12 months from the date that theseaudited financial statements, are issued. However, additional funding will be necessary to fund our MORE trial and to advance our proprietary combination therapy candidates through regulatory approval and into commercialization, if approved. Although we have been successful in raising capital in the past, there is no assurance that we will be successful in obtaining additional financing on terms acceptable to us, if at all, nor is it considered probable under the accounting standards.  If we are unable to obtain funding, we would be forced to delay, reduce or eliminate one or more of our research and development programs, product portfolio expansion or commercialization efforts, which would adversely affect our business prospects, or we may be unable to continue operations.as a going concern over the long-term.

Our actual cash requirements may vary materially from our current expectations. Should our operating plan may also change we will be required to reassess our operating capital needs and there can be no assurance that we will have the cash resources to fund any changed operating plan or that additional funding will be available on terms acceptable to us, if at all. Changing circumstances including those beyond our control may cause us to consume capital more rapidly than weas a result of many factors currently anticipate,unknown, and we may need to seek additional funds sooner than planned. For example, our clinical trials may encounter technical, enrollmentplanned, through public or private equity or debt financings, government or other difficulties that could increase our development costs more than we expect, or the FDA may require us or we may choose to perform studies or trials in addition to those that we currently anticipate. We may need to raise additional funds to support our ongoing programs for posenacaftor, dirocaftorthird-party funding, marketing and nesolicaftor, our proprietary combination therapy candidates,distribution arrangements and other clinical candidates, through regulatory approvalcollaborations, strategic alliances and commercialization,licensing arrangements, or ifa combination of these approaches. In any event, we need or opt to seekwill require additional capital to obtain regulatory approval for, posenacaftor and/and, if approved, to commercialize our product candidates. Raising funds in the current economic environment may present additional challenges. Even if we believe that we have sufficient funds for our current or nesolicaftor for administration with other CFTR modulators.future operating plans, we may seek additional capital if market conditions are favorable or if we have specific strategic considerations.

SecuringAny additional financingfundraising efforts may divert our management from our their day-to-day activities, which may adversely affect our ability to develop and, if approved, commercialize our product candidates, including posenacaftor, dirocaftor and nesolicaftor, and our proprietary combination therapy candidates. In addition, we cannot guarantee that future financing will be available in sufficient amounts or on terms acceptable to us,it, if at all. Moreover, the terms of any financing may adversely affect the holdings or the rights of our stockholders and the issuance of additional securities, whether equity or debt, by us, or the possibility of such issuance, may cause the market price of our shares to decline. The impactsale of COVID-19 on global financial markets may increase the likelihood that we are unable to raise capital. If we are unable to raise additional capital when requiredequity or on acceptable terms,convertible securities would dilute all of our stockholders. The incurrence of indebtedness would result in increased fixed payment obligations and we may be required to:

significantly delay, scale back or discontinue the research, development or commercialization of our product candidates, including posenacaftor, dirocaftor and nesolicaftor, our proprietary combination therapy candidates, and our other research or preclinical activities;

seek corporate partners for our proprietary combination therapy candidates, or any of our other product candidates at an earlier stage than otherwise would be desirable or on terms that are less favorable than might otherwise be available; or

relinquish, or license on unfavorable terms, our rights to technologies or product candidates that we otherwise would seekagree to develop or commercialize ourselves.

If we are unable to raise additional capital in sufficient amounts or on terms acceptable to us, we will be prevented from pursuing our development and commercialization efforts, which will have a material adverse effect on our business, operating results and prospects andcertain restrictive covenants, such as limitations on our ability to develop our product candidates. In addition, if we are unable to raise capital, we will also need to implement cost reductions, and any failure to effectively do so will harm our business, results of operations and prospects.

Raisingincur additional capital may cause dilution to our existing stockholders, restrict our operations or require us to relinquish rights to our technologies or product candidates on terms unfavorable to us.

Until such time, if ever, as we can generate substantial product revenues, we expect to finance our cash needs primarily through the sale of equity securities, debt, financings and government and foundation grants. We may also seek to raise capital through third-party collaborations, strategic alliances and similar arrangements. We currently do not have any committed external source of funds.

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In order to raise additional funds to support our operations, we may sell additional equity or debt securities, enter into collaborations, strategic alliances, or licensing arrangements or other marketing or distribution arrangements. For example, we have three effective universal shelf registration statements on Form S-3 pursuant to which we registered for sale up to $125.0 million, $100.0 million, and $200.0 million, respectively, of any combination of our common stock, preferred stock, debt securities, warrants, rights, purchase contracts and/or units from time to time and at prices and on terms that we may determine. As of May 7, 2020, an aggregate of approximately $324.4 million of securities remain available for issuance under the three shelf registration statements, including up to approximately $53.1 million of our common stock that we may offer and sell, from time to time, at our discretion, through H.C. Wainwright & Co., LLC, or HWC, as our sales agent under an at-the-market offering program sales agreement that we entered into with HCW in May 2019.  Our $125.0 million shelf registration statement supporting the ATM expires in July 2020, unless extended. We may choose not to file a new shelf registration, or we may choose not to continue using the ATM program at that time. To the extent that we raise additional capital through the sale of equity or debt securities, the ownership interest of existing stockholders will be diluted, and the terms of these securities may include liquidation or other preferences that adversely affect the rights of common stockholders. For example, our board of directors has the right to issue previously-authorized shares of preferred stock with such preferences without stockholder approval. Debt financing, if available, may involve the right to convert any such debt into equity on favorable conversion terms, which conversion would dilute existing stockholders’ ownership interest. Any such debt financing would also likely include covenants limiting or restricting our ability to take specific actions, such as incurring additional debt, making capital expenditures, and declaring dividends, and will impose limitations on our ability to acquire, sell or license intellectual property rights, and other operating restrictions that could adversely impact our ability to conduct our business.

If we raise additional We could also be required to seek funds through collaborations, strategic alliances, or licensing arrangements or other marketing or distribution arrangements with third parties,collaborative partners or otherwise at an earlier stage than otherwise would be desirable and we may havebe required to relinquish valuable rights to some of our technologies future revenue streams, research programs or product candidates or grant licensesotherwise agree to terms unfavorable to us, any of which may have a material adverse effect on terms that may not be favorable to us. our business, operating results, and prospects.

If we are unable to obtain funding on a timely basis, we may be required to significantly curtail, delay, or discontinue one or more of our research or development programs or the commercialization of any approved product candidate or be unable to expand our operations or otherwise capitalize on our business opportunities, as desired, which could materially affect our business, financial condition, and results of operations could be materially adversely affected. If we are unable to raise additional funds through equity or debt financings when needed, we may be required to delay, limit, reduce or terminate our product development or commercialization efforts, or grant others rights to develop and market product candidates that we would otherwise prefer to develop and market ourselves.operations.

The unpredictability of the capital markets may severely hinder our ability to raise capital within the time periods needed or on terms we consider acceptable, if at all. Furthermore, the impact of COVID-19 on global financial markets could make the terms of any available financing less attractive to us and more dilutive to our existing stockholders. Moreover, if we fail to advance one or more of our current product candidates to later-stage clinical trials, successfully commercialize one or more of our product candidates, or acquire new product candidates for development, we may have difficulty attracting investors that might otherwise be a source of additional financing.

We have a limited operating history, which may make it difficult to evaluate the success of our business to date and to assess our future viability.

We have not demonstrated an ability to perform the functions necessary for the successful commercialization of any product candidates.  The successful commercialization of any product candidates will require us to perform a variety of functions, including:

Continuing to undertake preclinical development and clinical trials;

Participating in regulatory approval processes;

Formulating and manufacturing products; and

Conducting sales and marketing activities.

We were formed and began operations in December 2006. Our operations to date have been limited to organizing and staffing our company, business planning, raising capital, acquiring and developing product and technology rights and conducting research and development activities for our product candidates. These operations provide a limited basis for you to assess our ability to commercialize our product candidates and the advisability of investing in our securities. We have not obtained regulatory approval for any of our product candidates. Consequently, any predictions about our future success, performance or viability may not be as accurate as they could be if we had a longer operating history, more experience with clinical development or approved products on the market.

The failure to maintain our license agreement with Genentech, Inc., or the failure of Genentech, Inc. to perform their obligations under the agreement, could negatively impact our business.

We are currently party to a technology transfer and license agreement with Genentech, Inc., or Genentech, in which we granted Genentech a worldwide, exclusive license for technology and materials relating to potential therapeutic small molecule modulators of an undisclosed target within the proteostasis network.  We have limited control over the timing and amount of resources that

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Genentech will dedicate to this arrangement. In particular, we will not be entitled to receive milestone or royalty payments from Genentech absent further development and eventual commercialization of medicines resulting from this license agreement.

We are subject to a number of other risks associated with our dependence on our license agreement with Genentech, including:

Genentech may not comply with applicable regulatory requirements with respect to developing or commercializing products under the license agreement, which could adversely impact development, regulatory approval and eventual commercialization of such products;

we and Genentech could disagree as to future development plans and Genentech may delay initiation of clinical trials or stop a future clinical trial;

there may be disputes between us and Genentech, including disagreements regarding the terms of the license agreement, that may result in the delay of or failure to achieve development, regulatory and commercial objectives that would result in milestone or royalty payments to us, the delay or termination of any future development or commercialization of licensed products using our technology, and/or costly litigation or arbitration that diverts our management’s attention and resources;

Genentech may not provide us with timely and accurate information regarding development progress and activities under the license agreement, which could adversely impact our ability to report progress to others, including our investors, and otherwise plan our own development of our product candidates;

Genentech may fail to meet expected timelines, which could result in the delay of or failure to achieve development, regulatory and commercial objectives;

business combinations or significant changes in Genentech’s business strategy may adversely affect Genentech’s ability or willingness to perform its obligations under the license agreement;

our license partners and potential license partners may not properly maintain or defend our intellectual property rights in their licensed fields or territories or may use our proprietary information in such a way as to invite litigation that could jeopardize or invalidate our intellectual property rights or expose us to potential litigation;

the royalties we are eligible to receive from Genentech may be reduced or eliminated based upon their and our ability to maintain or defend our intellectual property rights; and

our license partners and potential license partners may be impacted by external business disruptions resulting from geopolitical actions, including war and terrorism, natural disasters including earthquakes, typhoons, floods and fires, or from economic or political instability, or public health emergencies, such as the novel COVID-19 coronavirus and related shelter-in-place orders, travel, social distancing and quarantine policies, boycotts, curtailment of trade and other business restrictions.

This license agreement is subject to early termination, including through Genentech’s right to terminate without cause upon advance notice to us. If the agreement is terminated early, we may not be able to find another licensee for the technology and materials relating to potential therapeutic small molecule modulators of an undisclosed target within the proteostasis network, on acceptable terms, or at all, and we may otherwise be unable to pursue continued development on our own for these indications.

Furthermore, certain of the above risks and uncertainties may be amplified as a result of the impact of COVID-19. The extent to which COVID-19 may impact our license agreement with Genentech, or any other third-party partner, will depend on future developments, which are highly uncertain and cannot be predicted, including new information which may emerge concerning the severity of COVID-19 and the actions to contain COVID-19 or treat its impact, among others.

Risks Related to theOur Product Development and Regulatory ApprovalCommercialization

Research and development of Our Product Candidatesbiopharmaceutical products is inherently risky.

The effectsWe are at an early stage of health epidemics, including the global coronavirus pandemic, in regions where we, or the third parties on which we rely, have business operations could have a material adverse impact on our business, including our clinical trials, preclinical studies, supply chain and manufacturing, as well as third-parties which whom we conduct business.

Our business could be adversely affected by public health crises such as pandemics or similar outbreaks in regions where we have concentrations of clinical trial sites or other business operations, and could cause significant disruption in the operations of third party manufacturers and contract research organizations, or CROs, upon whom we rely. In December 2019, a novel strain of coronavirus, SARS-CoV-2, which causes coronavirus disease 2019 or COVID-19, surfaced in Wuhan, China. Since then, COVID-19 has spread to multiple countries, including the United States, Israel and many other European countries in which we have planned or ongoing clinical trials. Our company headquarters is located in Boston, and our CROs and CMOs are located in the United States and abroad. In March 2020, the World Health Organization declared the COVID-19 outbreak a pandemic, and the U.S. government imposed travel restrictions on travel between the United States, Europe and certain other countries. Further, the Presidentdevelopment of the United States declared the COVID-19 pandemic a national emergency, invoking powers under the Stafford Act, the legislation that directs federal emergency disaster response. In addition, on March 23, 2020, the Governor of Massachusetts ordered all individuals living in the Commonwealth of Massachusetts to stay at their place of residence for an indefinite period of time (subject to certain exceptions to facilitate authorized necessary activities) to mitigate the impact of the COVID-19 pandemic. The executive order exempts certain

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individuals needed to maintain continuity of operations of critical infrastructure sectors as determined by the federal government, and the Governor has clarified to MassBio that all biopharma research and development is essential and exempt.

In response to the spread of COVID-19 as well as public health directives and orders, we have implemented work-from-home policies to support the community efforts to reduce the transmission of COVID-19 and protect employees, complying with guidance from federal, state or municipal government and health authorities. We implemented a number of measures to ensure employee safety and business continuity. We have closed our offices with our administrative employees continuing their work outside of our offices, restricted on-site staff to only those required to execute their job responsibilities and limited the number of staff in any given research and development laboratory. Business travel has been suspended, and online and teleconference technology is used to meet virtually rather than in person. We have taken measures to secure our research and development project activities, and work in has been minimized to reduce the risk of COVID-19 transmission.

The regions in which we operate areproduct candidates currently being affected by COVID-19.  Further, timely enrollment in our clinical trials is dependent upon global clinical trial sites which may be adversely affected by COVID-19. Wepipeline and are currently planning for new clinical trials for ourcontinuing to discover additional potential product candidates in countries, including the U.S. and throughout the E.U. Shutdowns or other restrictions related to COVID-19 or other infectious diseases could impact personnel at third-party manufacturing facilities in the United States and other countries, or the availability or cost of materials, which would disruptleveraging our supply chain. Additionally, many of our clinical trials involve patients who have severe medical conditions and are at higher risk for COVID-19 and who are therefore more likely to avoid hospitals or other high-risk areas.

The effects of the executive orders and our work-from-home policies may negatively impact productivity, disrupt our business and delay our clinical programs and timelines (for example, our timelines for any of our product candidates), the magnitude of which will depend, in part, on the length and severity of the restrictions and other limitations on our ability to conduct our business in the ordinary course.

Quarantines, shelter-in-place and similar government orders, or the perception that such orders, shutdowns or other restrictions on the conduct of business operations could occur, related to COVID-19 or other infectious diseases could impact personnel at third-party manufacturing facilities in the United States and other countries, or the availability or cost of materials, which would disrupt our supply chain.

As a result of the COVID-19 outbreak, or similar pandemics, we may experience disruptions that could severely impact our business, clinical trials and preclinical studies, including:

delays or difficulties in enrolling and maintaining patients in our clinical trials, including patients that may not be able or willing to comply with clinical trial protocols if quarantines impede patient movement or interrupt healthcare services;

delays or difficulties in clinical site initiation, including difficulties in recruiting clinical site investigators and clinical site staff;

delays or disruptions in non-clinical experiments and investigational new drug application-enabling good laboratory practice standard toxicology studies due to unforeseen circumstances in supply chain;

delays or disruptions in our ability to manufacture our product candidates due to supply chain disruptions, lack of clinical staff or restrictions on the availability of shared hospital resources;

increased rates of patients withdrawing from our clinical trials following enrollment as a result of contracting COVID-19, being forced to quarantine, or being unable to visit clinical trial locations;

diversion or prioritization of healthcare resources away from the conduct of clinical trials and towards the COVID-19 pandemic, including the diversion of hospitals serving as our clinical trial sites and hospital staff supporting the conduct of our clinical trials, and because, who, as healthcare providers, may have heightened exposure to COVID-19 and adversely impact our clinical trial operations;

interruption of our key clinical trial activities, such as clinical assessments at pre-specified timepoints during the trial and clinical trial site data monitoring, due to limitations on travel imposed or recommended by governmental entities, employers and others or interruption of clinical trial subject visits and study procedures (particularly any procedures that may be deemed non-essential), which may impact the integrity of subject data and clinical study endpoints;

interruption or delays in the operations of the FDA, European Medicines Agency, or EMA, and comparable foreign regulatory agencies or their refusal to accept data from clinical trials in affected geographies, which may impact approval timelines;

delays in necessary interactions with local regulators, ethics committees and other important agencies and contractors due to limitations in employee resources or forced furlough of government employees;

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limitations on employee resources that would otherwise be focused on the conduct of our clinical trials, including sickness of employees or their families, the desire of employees to avoid contact with large groups of people, an increased reliance on working from home or mass transit disruptions; and

reduced ability to engage with the medical and investor communities due to the cancellation of conferences scheduled throughout the year.

discovery engine platform. To date, we have already experienced certain disruptions, including the closuredevoted substantially all of certain facilities in Europeour efforts and delays in ex vivo testing of organoids. Such disruptions could leadfinancial resources to a delay in patient selectionidentify, secure intellectual property for, and recruitment. Such delay could result in broader impact todevelop our contemplated timeline and clinical trial generally.

These and other factors arising from the COVID-19 pandemic could worsen in countries that are already afflicted with COVID-19, could continue to spread to additional countries, or could return to countries where the pandemic has been partially contained, each of which could continue to adversely impact our ability to conduct clinical trialsdiscovery engine platform and our business generally, and could have a material adverse impact on our operations and financial condition and results.

In addition, the trading price for our common stock and other biopharmaceutical companies, as well as the broader equity and debt markets, have been highly volatile as a result of the COVID-19 pandemic and the resulting impact on global financial markets. As a result, we may face difficulties raising capital when needed, and any such sales may be on unfavorable terms to us. Further, to the extent we raise additional capital through the sale of equity or convertible debt securities, the ownership interest of existing shareholders will be diluted.

The global outbreak of the COVID-19 coronavirus continues to rapidly evolve. The extent to which the outbreak may impact our business, clinical trials andproduct candidates, including conducting multiple preclinical studies, will depend on future developments, which are highly uncertain and cannot be predicted with confidence, such as the ultimate geographic spread of COVID-19, the duration of the outbreak, travel restrictionsproviding general and actions to contain the outbreak or treat its impact, such as social distancing and quarantines or lock-downs in the United States and other countries, business closures or business disruptions and the effectiveness of actions taken in the United States and other countries to contain and treat the disease.

We depend substantially on the success of our lead product candidates, posenacaftor, dirocaftor and nesolicaftor, which are currently in clinical development. We cannot be certain that we will be able to successfully complete the clinical development of, obtain regulatory approvaladministrative support for or successfully commercialize posenacaftor, dirocaftor and nesolicaftor.

We currently have no products on the market, and our most advanced product candidates, posenacaftor, dirocaftor and nesolicaftor, are currently in clinical development.

these operations. Our business depends substantiallyheavily on the successful clinical development, regulatory approval, and commercialization of posenacaftor, dirocaftorour lead product candidate, YTX-7739 which is in clinical development. None of our product candidates have advanced into late-stage development or a pivotal clinical study and nesolicaftor, and theyit may be years before any such study is initiated, if at all. YTX-7739 will require substantial additional clinical development, testing, and regulatory approval efforts before we are permitted to commence commercialization, if ever. Theour commercialization. Further, we cannot be certain that any of our product candidates will be successful in clinical trials or obtain regulatory approval.

Our future success is dependent on our ability to successfully develop, obtain regulatory approval for, and then successfully commercialize our product candidates, and we may fail to do so for many reasons, including the following:

our product candidates may not successfully complete preclinical studies or clinical trials;

a product candidate may, upon further study, be shown to have harmful side effects or other characteristics that indicate it is unlikely to be effective or otherwise does not meet applicable regulatory criteria;

our competitors may develop therapeutics that render our product candidates obsolete or less attractive;

our competitors may develop platform technologies that render our platform technology obsolete or less attractive;

the product candidates that we develop and our discovery engine platform may not be sufficiently covered by intellectual property for which we hold exclusive rights;

the market for a product candidate may change so that the continued development of that product candidate is no longer reasonable or commercially attractive;

a product candidate may not be capable of being produced in commercial quantities at an acceptable cost, or at all;

we may not be able to establish manufacturing capabilities or arrangements with third-party manufacturers for clinical and, if approved, commercial study;

even if a product candidate obtains regulatory approval, we may be unable to establish sales and marketing capabilities, or successfully market such approved product candidate, to gain market acceptance; and

a product candidate may not be accepted as safe or effective by patients, the medical community or third-party payors, if applicable.

If any of these events occur, we may be forced to abandon our development efforts for a product candidate or candidates, which would have a material adverse effect on our business and could potentially cause us to cease operations. For instance, if we observe harmful side effects or other characteristics that indicate one product candidate is unlikely to be effective or otherwise does not meet applicable regulatory criteria, these findings may implicate the discovery engine platform as a whole.

We may not be successful in our efforts to further develop our discovery engine platform technology and current product candidates. We are not permitted to market or promote any of our product candidates before we receive regulatory approval from the FDA or comparable foreign regulatory authorities, and we may never receive such regulatory approval for any of our product candidates. Each of our product candidates are in the early stages of development and will require significant additional clinical development, management of preclinical, clinical, and manufacturing activities, regulatory approval, adequate manufacturing supply, a commercial organization, and significant marketing efforts before we could generate any revenue from product sales, if at all.

The preclinical and clinical product candidates and current clinical trials are, and the future clinical trials and the manufacturing and marketing of posenacaftor, dirocaftor and nesolicaftor and any otherour product candidates will be, subject to extensive and rigorous review and regulation by numerous government authorities in the U.S., the E.U.United States, and in other jurisdictionscountries where we intend to test and, if approved, market ourany product candidates.candidate. Before obtaining regulatory approvals for the commercial sale of any product candidate, we must, among other requirements, demonstrate through preclinical testingstudies and clinical trials that the product candidate is safe and effective for use in each target indication,indication. Drug development is a long, expensive, and potentially in specific patient populations, including the pediatric population.uncertain process, and delay or failure can occur at any stage of any of our clinical trials. This process can take many years and may include post-marketing studies and surveillance, which wouldwill require the expenditure of substantial resources beyond the proceeds we have currently raised.resources. Of the large number of drugs in development for approval in the United States, and the European Union, only a small percentage will successfully complete the FDA or EMA, regulatory approval processes, as applicable,process and arewill be commercialized. Accordingly, even if we are able to obtain the requisite financing to continue to fund our research, development and preclinical studies and clinical programs,trials, we cannot assure you that posenacaftor, dirocaftor, nesolicaftor or any of our other product candidates will be successfully developed or commercialized.

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We also depend on the successIf any of our proprietary combination therapies, includingproduct candidates successfully complete clinical trials, we generally plan to seek regulatory approval to market our product candidates in the United States, the European Union (“EU”), and in additional foreign countries where we believe there is a doubleviable commercial opportunity and a triple combination,significant patient need. We have never commenced, compiled, or submitted an application seeking regulatory approval to market any product candidate. We may never receive regulatory approval to market any product candidates even if such product candidates successfully complete clinical trials, which are currentlywould adversely affect our viability. To obtain regulatory approval in earlycountries outside the United States, we must comply with numerous and varying regulatory requirements of such other countries regarding safety, efficacy, chemistry, manufacturing and controls, clinical development.trials, commercial sales, pricing, and distribution of our product candidates. We may also rely on collaborators or partners to conduct the required activities to support an application for regulatory approval, and to seek approval, for one or more of our product candidates. We cannot be certainsure that any collaborators or partners will conduct these activities or do so within the timeframe we desire. Even if we (or any collaborators or partners) are successful in obtaining approval in one jurisdiction, we cannot ensure that we (or any collaborators or partners) will obtain approval in any other jurisdictions. If we are unable to obtain approval for our product candidates in multiple jurisdictions, our revenue and results of operations could be negatively affected.

Even if we receive regulatory approval to market any of our product candidates, we cannot assure you that any such product candidate will be successfully commercialized, widely accepted in the marketplace or more effective than other commercially available alternatives.

Investment in biopharmaceutical product development involves significant risk that any product candidate will fail to demonstrate adequate efficacy or an acceptable safety profile, gain regulatory approval, and become commercially viable. We cannot provide any assurance that we will be able to successfully completeadvance any of our product candidates through the development process or, if approved, successfully commercialize any of our product candidates.

We may not be successful in our efforts to continue to create a pipeline of product candidates or to develop commercially successful products. If we fail to successfully identify and develop additional product candidates, our commercial opportunity may be limited.

One of our strategies is to identify and pursue clinical development of obtain regulatory approval for, or successfully commercialize these combinations. Combination therapies involve additional complexityproduct candidates. Our portfolio currently consists of four programs, one of which is in clinical development and risk that could delay or cause our programs to stall or fail; developmentthe rest of such programs may be more costly, may take longer to achievewhich are in research, discovery and preclinical stages of development. Identifying, developing, obtaining regulatory approval, and may be associated with unanticipated adverse events.

Our business depends oncommercializing additional product candidates for the successful clinical development, regulatory approval and commercializationtreatment of combination therapies, including potential proprietary double and triple combinations thatneurodegenerative diseases will require substantial additional funding and is prone to the risks of failure inherent in drug development. We cannot provide you any assurance that we will be able to successfully identify or acquire additional product candidates, advance any of these additional product candidates through the development process, successfully commercialize any such additional product candidates, if approved, or assemble sufficient resources to identify, acquire, develop or, if approved, commercialize additional product candidates. If we are unable to successfully identify, acquire, develop, and commercialize additional product candidates, our commercial opportunity may be limited.

We may not be able to conduct, or contract others to conduct, animal testing in the future, which could harm our research and development activities.

Certain laws and regulations relating to drug development require us to test our product candidates on animals before initiating clinical trials involving humans. Animal testing activities have been the subject of controversy and adverse publicity. Animal rights groups and other organizations and individuals have attempted to stop animal testing activities by pressing for legislation and regulation in these areas and by disrupting these activities through protests and other means. To the extent the activities of these groups are successful, our research and development activities may be interrupted or delayed.

We have concentrated our research and development efforts on the treatment of neurodegenerative diseases, a field that has seen limited success in drug development. Further, our product candidates are based on new approaches and novel technology, which makes it difficult to predict the time and cost of product candidate development and subsequently obtaining regulatory approval.

We have focused our research and development efforts on addressing neurodegenerative diseases, including Parkinson’s disease, ALS and Alzheimer’s disease. Efforts by biopharmaceutical companies in the field of neurodegenerative diseases have seen limited successes in drug development. There are few effective therapeutic options available for patients with Parkinson’s disease, ALS or Alzheimer’s disease. Our future success is highly dependent on the successful development of our discovery engine platform technology and our product candidates for treating neurodegenerative diseases. Developing and, if approved, commercializing our product candidates for treatment of neurodegenerative diseases subjects us to a number of challenges, including engineering product candidates and obtaining regulatory approval efforts beforefrom the FDA and other regulatory authorities who have only a limited set of precedents to rely on.

Our approach is centered on the key insight that human protein misfolding, a phenomenon at the root of virtually all neurodegenerative diseases, can be modeled effectively in yeast cells. Discoveries from the yeast system are then translated to diseased human cell lines created by adult stem cells using induced pluripotent stem cell technology (“iPSC”). This strategy may not prove to be successful. We cannot be sure that our approach will yield satisfactory therapeutic products that are safe and effective, scalable, or profitable.

Moreover, public perception of drug safety issues, including adoption of new therapeutics or novel approaches to treatment, may adversely influence the willingness of subjects to participate in clinical trials, or if approved, of physicians to prescribe our products.

We may encounter difficulties in enrolling subjects in our clinical trials, thereby delaying or preventing development of our product candidates.

There is no precise method of establishing the actual number of people with neurodegenerative diseases in any geography over any time period. It is estimated that more than 60 million people worldwide suffer from neurodegenerative diseases. If the actual number of people with neurodegenerative diseases is lower than we are permittedbelieve, we may experience difficulty in enrolling subjects in our clinical trials, thereby delaying development of our product candidates. Furthermore, we may experience difficulties in subject enrollment in our clinical trials for a variety of other reasons, including:

the subject eligibility criteria defined in the protocol, including biomarker-driven identification and/or certain highly-specific criteria related to commence commercialization, if ever. Thestage of disease progression, which may limit the patient populations eligible for our clinical trials to a greater extent than competing clinical trials for the same indication that do not have biomarker-driven patient eligibility criteria;

eligibility requirements mandated by regulatory agencies which may limit the number of eligible patients in a given disorder;

the size of the study population required for analysis of the study’s primary endpoints;

the proximity of subjects to a study site;

the design of the study;

our use of academic sites, which may be less accustomed to running clinical trials and manufacturingmanaging enrollment;

public perception of drug safety issues;

our ability to recruit clinical study investigators with the appropriate competencies and marketingexperience;

competing clinical trials for similar therapies or targeting patient populations meeting our patient eligibility criteria;

clinicians’ and patients’ perceptions as to the potential advantages and side effects of these combinationsthe product candidate being studied in relation to other available therapies and product candidates;

our ability to obtain and maintain patient consents;

the risk that subjects enrolled in clinical trials will be subjectnot complete such studies, for any reason; and

the impact of the COVID-19 pandemic on patient enrollment and retention and clinical trial site initiation.

Our clinical trials may fail to extensivedemonstrate adequate safety and rigorous reviewefficacy of our product candidates, which would prevent, delay, or limit the scope of regulatory approval and regulation by numerous government authorities in the United States, the European Union and other jurisdictions where we intend to test and, if approved, market them. commercialization.

Before obtaining regulatory approvals for the commercial sale of any of our product candidate,candidates, we must, among other requirements, demonstrate through lengthy, complex, and expensive preclinical testingstudies and clinical trials that theour product candidate iscandidates are both safe and effective for use in each target indication,indication. Each product candidate must demonstrate an adequate risk versus benefit profile in our intended patient population and potentially in specific patient populations, including the pediatric population. This processfor our intended use.

Clinical testing is expensive and can take many years to complete, and our outcome is inherently uncertain. Failure can occur at any time during the clinical study process. The results of preclinical studies of our product candidates may include post-marketingnot be predictive of the results of early-stage or later-stage clinical trials, and results of early-stage clinical trials of our product candidates may not be predictive of the results of later-stage clinical trials. The results of clinical trials in one set of subjects or disease indications may not be predictive of those obtained in another. In some instances, there can be significant variability in safety or efficacy results between different clinical trials of the same product candidate due to numerous factors, including changes in study procedures set forth in protocols, differences in the size and type of the patient populations, changes in and lack of adherence to the dosing regimen and other clinical study protocols, and the rate of dropout among clinical study participants. Product candidates in later stages of clinical trials may fail to show the desired safety and efficacy profile despite having progressed through preclinical studies and surveillance, which would require the expenditure of substantial resources beyond the proceeds we have currently raised. Of the largeinitial clinical trials. A number of drugs in development for approvalcompanies in the United States and the European Union, only a small percentage successfully complete the FDAbiopharmaceutical industry have suffered significant setbacks in later-stage clinical trials due to lack of efficacy or European Medicines Agency, or EMA, regulatory approval processes, as applicable, and are commercialized. Accordingly, even if we are able to obtain the requisite financing to continue to fund our research, development and clinical programs, we cannot assure you that our proprietary combination therapies or any of oursafety issues, notwithstanding promising results in early-stage studies. This is particularly true in neurodegenerative diseases, where failure rates historically have been higher than in other disease areas. Most product candidates will be successfully developed or commercialized.that begin clinical trials are never approved by regulatory authorities for commercialization.

Clinical development and commercialization of combination therapies, such as our potential proprietary double and triple combinations, involve additional complexity and risk, including without limitation, those involving preclinical studies, drug-drug interactions, dose selection, unanticipated adverse events, clinical design and approvals of regulatory bodies and therapeutic development networks of patient advocacy groups. For example, if we or regulatory bodies identify concerns in preclinical and/or combination toxicology studies, we may need to run additional studies before commencing or continuing clinical development. Combination therapy clinical development may also involve more restrictive inclusion criteria based on the profiles of multiple investigational products, which could delay enrollment.

We have limited experience developingin designing clinical trials and commercializing combination therapies and are competing with industry players with greater resources than us. If we aremay be unable to manage the additional complexitiesdesign and risks of the development and commercialization of combination therapies,execute a clinical study to support marketing approval. We cannot be certain that our proposed combination program could be delayed, halted or otherwise fail to receive approval.

The regulatory approval processes of the FDA and comparable foreign regulatory authorities are lengthy, time-consuming and inherently unpredictable. Agency requirements that differ from our assumptions or change can result in delays in starting, conducting and finishingcurrent clinical trials that are needed before we can apply for the next phase of development and, if successful, marketing approvals. If we are ultimately unable to obtain regulatory approval for our product candidates, our businessor any other future clinical trials will be substantially harmed.

We are not permitted to market posenacaftor, dirocaftor, nesolicaftor, our potential combination therapies, orsuccessful. Additionally, any safety concerns observed in any one of our other product candidatesclinical trials in our targeted indications could limit the United States or the European Union until we receiveprospects for regulatory approval of a New Drug Application, or NDA, from the FDA or a Marketing Authorization Application, or MAA, from the European Commission, respectively. Prior to submitting an NDA to the FDA or an MAA to the EMA for approval of any of our product candidates for a specific indication, we will need to complete preclinical and toxicology studies, as well as Phase 1, Phase 2 and Phase 3 clinical trials.

Successfully initiating and completing our clinical program and obtaining approval of an NDA or an MAA is a complex, lengthy, expensive and uncertain process, and the FDA, the EMA or other comparable foreign regulatory authorities may delay, limit or deny approval of any of our candidates for many reasons, including, among others:

we may not be able to demonstrate that our product candidates are safe and effective to the satisfaction of the FDA or the EMA;

the results of our clinical trials may not meet the level of statistical or clinical significance required by the FDA or the EMA for marketing approval;

the FDA or the EMA may disagree with the number, design, size, conduct or implementation of our clinical trials or the requirements for or adequacy of the information and data needed to support the next phase of development (including, without limitation, Phase 3) for one or more of our product candidates, such as our combination therapy candidates;

the FDA or the EMA may require that we conduct additional clinical trials or cohorts or run cohorts sequentially, all of which could delay our trial completion timelines;

the FDA or the EMA may not approve the formulation, labeling or specifications of posenacaftor, dirocaftor, nesolicaftor, or our other product candidates;

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the clinical research organizations, or CROs, that we retain to conduct our clinical trials may take actions outside of our control that materially adversely impact our clinical trials;

the FDA or the EMA may find the data from preclinical studies and clinical trials insufficient to demonstrate that posenacaftor, dirocaftor, nesolicaftor, our potential combination therapies, and/or our other product candidates’ clinicalin those, and other benefits outweigh their safety or other risks, including, without limitation, the potential for drug-drug interaction;

the FDA or the EMA may disagree with our interpretation of data from our preclinical studies and clinical trials, including our characterization of observed toxicities;

the FDA or the EMA may not accept data generated at our clinical trial sites;

if our NDAs or MAAs, if and when submitted, are reviewed by the FDA or the EMA, as applicable, the regulatory agency may have difficulties scheduling the necessary review meetings in a timely manner, may recommend against approval of our application or may recommend that the FDA or the EMA, as applicable, require, as a condition of approval, additional preclinical studies or clinical trials, limitations on approved labeling or distribution and use restrictions;

the FDA may require development of a Risk Evaluation and Mitigation Strategy as a condition of approval or post-approval, and the EMA may grant only conditional approval or impose specific obligations as a condition for marketing authorization, or may require us to conduct post-authorization safety studies;

the FDA or the EMA may find deficiencies with or not approve the manufacturing processes or facilities of third-party manufacturers with which we contract; or

the FDA or the EMA may change their approval policies or adopt new regulations.

Any of these factors, many of which are beyond our control, could jeopardize our ability to obtain regulatory approval for and successfully market posenacaftor, dirocaftor, nesolicaftor, our potential combination therapies, or any of our other product candidates. Any such setback in our pursuit of regulatory approval would have a material adverse effect on our business and prospects.

Disruptions at the FDA and any comparable agencies may also slow the time necessary for new drugs to be reviewed and/or approved by necessary government agencies, which would adversely affect our business. For example, in recent years, including in 2018 and 2019, the U.S. government shut down several times and certain regulatory agencies, such as the FDA and the SEC, had to furlough critical employees and stop critical activities. Separately, in response to the COVID-19 pandemic, on March 10, 2020, the FDA announced its intention to postpone most inspections of foreign manufacturing facilities and products through April 2020. On March 18, 2020, the FDA announced its intention to temporarily postpone routine surveillance inspections of domestic manufacturing facilities and provided guidance regarding the conduct of clinical trials. Regulatory authorities outside the United States may adopt similar restrictions or other policy measures in response to the COVID-19 pandemic. If a prolonged government shutdown occurs, or if global health concerns continue to prevent the FDA or other regulatory authorities from conducting their regular inspections, reviews, or other regulatory activities, it could significantly impact the ability of the FDA to timely review and process our regulatory submissions,indications, which could have a material adverse effect on our business.business, financial condition, and results of operations.

In addition, even if such clinical trials are successfully completed, we cannot guarantee that the FDA or foreign regulatory authorities will interpret the results as we do, and more studies could be required before we submit our product candidates for approval. To the extent that the results of the studies are not satisfactory to the FDA or foreign regulatory authorities for support of a marketing application, we may be required to expend significant resources, which may not be available to us, to conduct additional studies in support of potential approval of our product candidates. Even if regulatory approval is secured for any of our product candidates, the terms of such approval may limit the scope and use of our product candidates, which may also limit their commercial potential.

We may not be able to file IND applications or related amendments or similar applications and amendments outside the United States to commence additional clinical trials on the timelines expected, and even if we are able to, regulatory authorities may not permit us to proceed.

We may not be able to file future IND applications or similar applications outside the European Union, we intend to marketUnites States for our product candidates on the timelines we expect. For example, we may experience manufacturing delays or other delays with preclinical studies. Moreover, we cannot be sure that submission of an IND or similar application outside the United States will result in the FDA or respective regulatory authority allowing clinical trials to begin, or that, once begun, issues will not arise that suspend or terminate clinical trials. Additionally, even if approved,such regulatory authorities agree with the design and implementation of the clinical trials set forth in IND or similar application, we cannot guarantee that such regulatory authorities will not change their requirements in the future. These considerations also apply to new clinical trials we may submit as amendments to existing IND or similar applications or to a new application. Any failure to file IND or similar applications on the timelines we expect or to obtain regulatory authorizations for our trials may prevent us from completing our clinical trials or commercializing our products on a timely basis, if at all.

Interim, “topline,” and preliminary data from our clinical trials that are announced or published from time to time may change as more patient data become available and are subject to audit and verification procedures that could result in material changes in the final data.

From time to time, we may publicly disclose preliminary or topline data from our clinical trials, which are based on a preliminary analysis of then-available data, and the results and related findings and conclusions are subject to change following a more comprehensive review of the data related to the particular trial. We also make assumptions, estimations, calculations and conclusions as part of its analyses of data, and we may not have received or had the opportunity to fully evaluate all data. As a result, the topline or preliminary results that we report may differ from future results of the same studies, or different conclusions or considerations may qualify such results, once additional data have been received and fully evaluated. Topline data also remain subject to audit and verification procedures that may result in the final data being materially different from the preliminary data we previously published. As a result, topline data should be viewed with caution until the final data are available. From time to time, we may also disclose interim data from our clinical trials. Interim data from clinical trials that we may complete are subject to the risk that one or more of the clinical outcomes may materially change as patient enrollment continues and more patient data become available or as patients from our clinical trials continue other international markets. Such marketing will require separatetreatments for their disease. Adverse differences between preliminary or interim data and final data could significantly harm our business prospects.

In addition, the information we choose to publicly disclose regarding a particular clinical trial is based on what is typically extensive information, and you or others may not agree with what we determine is material or otherwise appropriate information to include in our disclosure.

If the interim, topline, or preliminary data that we report differs from actual or final results, or if others, including regulatory approvals in each market and complianceauthorities, disagree with numerous and varying regulatory requirements. The approval procedures vary from country-to-country and may require additional testing. Moreover, the time requiredconclusions reached, our ability to obtain approval may differ from that required to obtain FDA or EMA approval. In addition, in many countries, a product candidate must be approved for, reimbursement before it can be approved for sale in that country. Approval by the FDA or the EMA does not ensure approval by regulatory authorities in other countries or jurisdictions, and approval by one foreign regulatory authority does not ensure approval by regulatory authorities in other foreign countries or by the FDA or the EMA. The regulatory approval process in other international markets may include all of the risks associated with obtaining FDA or EMA approval.

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Our leadcommercialize, our product candidates are designed tomay be administered with other CF therapies. Developingharmed, which could harm our business, operating results, prospects or financial condition.

Our product candidates for administration withmay cause serious adverse events or other therapies may lead to unforeseenundesirable side effects or failures in our clinical trials that could delay or prevent their regulatory approval, or limit the commercial profile of an approved label.label, or result in significant negative consequences following marketing approval, if any.

We are exploring proprietary combination therapies consisting of combinations of posenacaftor and dirocaftor, as a double combination, and posenacaftor, dirocaftor and nesolicaftor, as a triple combination.  We anticipate that if oneSerious adverse events or more ofother undesirable side effects caused by our product candidates is approved for marketing, it may be approvedcould cause us or regulatory authorities to be administered withinterrupt, delay, or halt clinical trials, and could result in a more restrictive label or the delay or denial of regulatory approval by the FDA or other therapies. Our development programs and planned studies carry all the risks inherent in drug development activities, including the risk that they will fail to demonstrate meaningful efficacy or acceptable safety. In addition, our development programs are subject to additional regulatory commercial, manufacturing and other risks becauseauthorities.

Further, clinical trials by their nature utilize a sample of the potential usepatient population for a limited duration of other therapies in combinationexposure. Rare and severe side effects of a product candidate may only be uncovered with a significantly larger number of patients exposed to the product candidate. If our product candidates. Testingcandidates receive marketing approval and we or others identify undesirable side effects caused by such product candidates in combination with(or any other therapies may increase the risk of significant adverse effects or test failures, or impact from drug-drug interactions. The timing, outcome and cost of developing products to be used in combination with other therapies is difficult to predict and dependent onsimilar products) after such approval, a number of factors thatpotentially significant negative consequences could result, including:

regulatory authorities may suspend, withdraw, or limit their approval of such product candidates;

regulatory authorities may require the addition of labeling statements, such as a “boxed” warning or a contraindication;

we may be required to change the way such products are outside our reasonable control. If distributed or administered;

we may be required to conduct additional post-marketing studies and surveillance;

we may be required to implement a risk evaluation and mitigation strategy (“REMS”), or create a medication guide outlining the risks of such side effects for distribution to patients;

we may be subject to regulatory investigations and government enforcement actions;

subjects in a clinical study may experience safetysevere or toxicity issues in ourunexpected drug-related side effects;

we may decide, or regulatory authorities may require it, to conduct additional clinical trials or with any approved products, abandon product development programs;

we may not receive approvaldecide to market anyremove such products whichfrom the marketplace;

we could be sued and held liable for injury caused to individuals exposed to or taking our products;

the product may become less competitive; and

our reputation may suffer.

Any of these events could prevent us from ever generating revenuesachieving or achieving profitability.

If the data from our existing, ongoing and planned preclinical studies and clinical trials of posenacaftor, dirocaftor and nesolicaftor as part of a proprietary combination therapy, regarding the safety or efficacy of these combinations are not favorable, the FDA and comparable foreign regulatory authorities may not approve these combination therapies and we may be forced to delay or terminate the development of any of these combination therapies, which would materially harm our business. Further, even if we gain marketing approvals for any of these combination therapies from the FDA and comparable foreign regulatory authorities in a timely manner, we cannot be certain that they will be commercially successful. If the results of the anticipated or actual timing of marketing approvals for these combination therapies, or themaintaining market acceptance of these combination therapies, if approved, including treatment reimbursement levels agreed to by third-party payors, do not meet the expectations of investors or public market analysts,affected product candidates, could substantially increase the market price of our common stock would likely decline.  Government and other third-party payors seek to contain costs of health care through legislativecommercializing our product candidates, and other means. If they failcould significantly impact our ability to provide coveragesuccessfully commercialize our product candidates and adequate reimbursement rates for these products, it could increase the cost of our trials in such jurisdictions and decrease the possible market for any approved combination therapy that includes these co-administered drugs.generate revenues.

Failures or delays in the commencement progress or completion of, or ambiguous or negative results from, our clinical trials of our product candidates including due to competition from competing trials for CF patients, amended or additional trials or cohorts, lack of sufficient approvals including from the FDA, local regulatory and ethics bodies and those of therapeutic development networks of patient advocacy groups, or trial holds or stoppage due to interim results or safety concerns, could result in increased costs to us and could delay, prevent, or limit our ability to generate clinical trial data, advance our product candidates in the clinic, submit an NDA (or foreign equivalent) for any of our product candidates for U.S. or foreign marketing approval, derive revenue and continue our business.

Successful completion of the clinical trials for posenacaftor, dirocaftor, nesolicaftor, our proprietary combination therapy candidates, and our other candidates is a prerequisite to submitting an NDA to the FDA or a MAA to the EMA and, consequently, the ultimate approval and commercial marketing of posenacaftor, dirocaftor, nesolicaftor, our proprietary combination therapy candidates, and our other candidates in the United States and the European Union. Similar prerequisites apply in other foreign jurisdictions and for all of our product candidates in any jurisdiction. Clinical trials are expensive, difficult to design and implement, can take many years to complete and are uncertain as to outcome. A product candidate can unexpectedly fail at any stage of clinical development. The historical failure rate for product candidates is high due to scientific feasibility, safety, tolerability, toxicology, efficacy, changing standards of medical care and other variables. If the FDA requires us to complete, or we choose to implement, amended or additional studies beyond what we currently expect or assume, or to run additional cohorts or conduct cohorts sequentially, we may be delayed in completing our clinical trials and our expenses will increase. Conducting our trials in Europe and other ex-U.S. jurisdictions has and will continue to require IND-equivalent submissions to, and the approval of, local regulatory and ethics bodies, and we cannot assure you we will receive these approvals, or receive them in a timely manner. If therapeutic development networks of CF patient advocacy groups in the United States and/or other jurisdictions such as Europe do not timely sanction or highly rate or score our trials, or prioritize trials of other sponsors over our trials, we may not be able to enroll sufficient patients to conduct our trials at their member sites, or it may take longer to conduct these trials and we may need to look to other jurisdictions where we can more efficiently run our trials.  Many CF clinical trial sites place importance on the review, ranking and sanctioning of therapeutic development networks of CF patient advocacy groups. In the U.S., we believe many sites consider sanctioning from the Protocol Review Committee, or PRC, of the Therapeutic Development Network of the U.S.-based Cystic Fibrosis Foundation, or the TDN, when deciding whether and when to participate in a trial or which trials to prioritize. For example, the TDN deferred sanctioning of nesolicaftor, which we believe contributed to a delay in our now completed nesolicaftor Phase 2 trial. There is also a large number of CF programs in clinical development at this time, including numerous corrector and combination trials from Vertex, and other companies with greater resources and experience than us.  We face intense competition for eligible CF patients, which has and could continue to hamper our recruitment efforts. We do not know whether allany of our clinical trials will begin or be completed on schedule, if at all, as the commencement and completion of clinical trials can be delayed or prevented for a number of reasons, including, among others:

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the FDA or other regulatory bodies may not authorize us or our investigators to commence our planned clinical trials or any other clinical trials we may initiate, or may suspend our clinical trials, for example, through imposition of a clinical hold;

delays in filing or receiving approvals of additional investigational new drug (“IND”) applications that may be required;

lack of adequate funding to continue our clinical trials and preclinical studies;

negative results from our preclinical studies and clinical trials;

delays in reaching or failing to reach agreement on acceptable terms with prospective contract research organizations (“CROs”) and clinical study sites, the terms of which can be subject to extensive negotiation and may vary significantly among different CROs and study sites;

 

delays in reaching or failing to reach agreement on acceptable terms with prospective CROs and trial sites, the terms of which can be subject to extensive negotiation and may vary significantly among different CROs and trial sites;

inadequate quantity or quality of or access to a product candidate or other materials necessary to conduct clinical trials;trials, for example delays in the manufacturing of sufficient supply of finished drug product;

difficulties obtaining institutional review board, or IRB, or ethics committee or EC,Institutional Review Board (“IRB”) approval to conduct a clinical trialstudy at a prospective site or sites;

challenges in recruiting and enrolling patientssubjects to participate in clinical trials, including the size and nature of the patient population, the proximity of patientssubjects to clinicalstudy sites, (including, without limitation, if U.S. trial sites include international subjects coming to the U.S. on a visa), eligibility criteria for the clinical trial,study, the nature of the clinical trialstudy protocol, (including, without limitation, patient factors such as the time commitment involved in the required number of trial-related visits and procedures and the inability to take certain existing therapies during the trial), risks included in the signed informed consent and any new or amended consents required by each study participant, the availability of approved effective treatments for the relevant disease, and competition from other clinical trialstudy programs for similar indications;

unfavorable review of or a decision to defer sanctioning or not to sanction one or more of our clinical trials by the TDN, or the CTN, each of which may not sanction our trials for conduct at prospective trial sites, may change or alter any approval it may grant, or may provide a ranking or revised ranking of an amended protocol that adversely impacts recruitment in our clinical trials compared with other investigational new drugs in CF; while the TDN approved and favorably ranked our proprietary triple combination (for posenacaftor, dirocaftor and nesolicaftor), proprietary double combination (for posenacaftor and dirocaftor), posenacaftor protocols as well as our posenacaftorand nesolicaftor trials in patients on background Symdeko, we cannot assure you that it will sanction any of our other trials; the CTN has approved and favorably ranked the protocols for our posenacaftor, nesolicaftor and triple combination trials and we are actively working to continue to expand into Europe with its member sites, subject to regulatory and ethics approvals in local jurisdictions, but we cannot assure you that such expansion will be successful

severe or unexpected drug-related side effects experienced by patientssubjects in oura clinical study;

we may decide, or regulatory authorities may require it, to conduct additional clinical trials or by individuals using drugs similarabandon product development programs;

delays in validating, or inability to validate, any endpoints utilized in a clinical study, if necessary;

the FDA may disagree with our product candidates;clinical study design and our interpretation of data from clinical trials, or may change the requirements for approval even after it has reviewed and commented on the design for our clinical trials;

reports from preclinical or clinical testing of other similaralpha-synuclein-dependent therapies that raise safety or efficacy concerns; orand

difficulties retaining and/or obtaining data from patientssubjects who have enrolled in a clinical trialstudy but may be prone to withdraw due to rigors of the clinical trial, lack of efficacy, side effects, personal issues, or loss of interest, difficulty travelling to the trial site or returning for required check-ins, or other factors, some of which are out of our control.interest.

There are an unprecedented number of CF clinical trials ongoing in the United States and in other countries. As a result of this and other factors described above, the activation of clinical trial sites for our ongoing trials, and securing our target subject enrollment for these clinical trials, has been delayed from what we had originally planned. If we are unable to increase our enrollment, we will not have a substantially complete data set for these trials by our target dates.

Clinical trials may also be delayed or terminated as a result of ambiguous or negative interim results. In addition, a clinical trialstudy may be suspended placed on clinical hold or terminated by us, the FDA, other regulatory authoritiesthe IRBs or the IRBs/ECsethics committees at the sites where the IRBs/ECsin which such clinical studies are overseeingbeing conducted, a clinical trial, or a data and safety monitoring board (“DSMB”) overseeing the clinical study at issue or DSMB, may recommend that the sponsor suspend or terminate a trial,other regulatory authorities due to a number of factors, including, among others:

failure to conduct the clinical trialstudy in accordance with regulatory requirements or our clinical protocols;

inspection of the clinical trialstudy operations or trialstudy sites by the FDA the EMA or other regulatory authorities that reveals deficiencies or violations that require us to undertake corrective action, including in response to the imposition of a clinical hold;

unforeseen safety issues, including any that could be identified in our ongoing toxicologypreclinical studies or clinical trials, adverse side effects or lack of effectiveness, including as part of ambiguous or negative interim results;effectiveness;

changes in government regulations or administrative actions;

problems with clinical supply materials; and

lack of adequate funding to continue clinical trials.

We may in the clinical trial.

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Positive results from preclinicalfuture seek orphan drug designation or in vitro, in vivo and ex vivo testingexclusivity for certain of our product candidates are not necessarily predictive of the results of our ongoing and future clinical trials of these candidates. If we cannot achieve positive results in our clinical trialscompetitors are able to obtain orphan drug exclusivity for products that constitute the same drug and treat the same indications as our proprietaryproduct candidates, or our other candidates, we may be unable to successfully develop, obtain regulatory approval for and commercialize our proprietary candidates.

Positive results from our preclinical testing of posenacaftor, dirocaftor, nesolicaftor, our proprietary combination therapy candidates, and our other candidates in vitro, in vivo and ex vivo may not necessarily be predictive of the results from our clinical trials in humans (including, without limitation, as part of any predicted correlation between in vitro CFTR protein activity as measured by an Ussing Chamber Assay and lung function improvement measured by FEV1 improvement in clinical trials). Many companies in the pharmaceutical and biotechnology industries have suffered significant setbacks in clinical trials after achieving positive results in preclinical in vitro and in vivo studies, and we may face similar setbacks in our ex vivo organoid studies. For example, CFTR mRNA levels in target tissues of rats and monkeys exposed to nesolicaftor were observed to increase proportionally with exposure to nesolicaftor. Additionally, preliminary exploratory biomarker nasal CFTR mRNA and protein data from the SAD and MAD cohorts in our Phase 1 clinical trial for nesolicaftor in healthy volunteers and nesolicaftor as an add-on agent to Symdeko confirm target engagement. However, later clinical trials may not show that this biomarker is predictive of clinical efficacy or we may not be able to successfully obtain sufficient biomarker data to analyze. Preclinical and clinical data are often susceptible to varying interpretations and analyses, andhave competing products approved by the FDAapplicable regulatory authority for a significant period of time.

We may in the future seek orphan drug designation or other regulatory agencies may require changes to our protocols or other aspects of our clinical trials or require additional studies. Additionally, many companies that believed their product candidates performed satisfactorily in preclinical studies and clinical trials nonetheless failed to obtain FDA or EMA approval. If we fail to produce positive results in our clinical trials of one or moreexclusivity for certain of our product candidates, the development timeline and regulatory approval and commercialization prospects for those product candidates, and, correspondingly, our business and financial prospects, would be materially adversely affected.  These risks could also impair our ability to successfully commence, progress or complete studies of our proprietary combination therapy candidates.

Even if we obtain positive clinical results for our proprietary candidates in early-stage clinical trials (including, without limitation, those involving a relatively short duration in a small number of subjects, with the publication of interim, initial, preliminary or final results), those positive results may not be repeated in later-stage clinical trials.  

Before obtaining regulatory approval for the sale of our product candidates, including posenacaftor, dirocaftor, nesolicaftor, and any proprietary combination therapy candidates, we must conduct extensive clinical trials to demonstrate the safety and efficacy of our product candidates in humans. Successful completion of such clinical trials is a prerequisite to submitting an NDA to the FDA and, consequently, the ultimate approval and commercial marketing of posenacaftor, dirocaftor and nesolicaftor and any proprietary combination therapy candidates in the United States. Similar requirements apply in the European Union and other foreign jurisdictions. A failure of one or more clinical trials can occur at any stage of testing. The outcome of preclinical testing and early clinical trials may not be predictive of the success of later clinical trials, and preliminary, initial or interim results of a clinical trial do not necessarily predict final results. Our current CF trials involve relatively short duration in a small number of patients, resulting in limited data sets. From time to time, we may publish or report interim, initial or preliminary data from our clinical trials. Interim, initial or preliminary data from clinical trials that we may conduct may not be indicative of the final results of the trial and are subject to the risk that one or more of the clinical outcomes may materially change as patient enrollment continues and more patient data become available. Interim, initial or preliminary data also remain subject to audit and verification procedures that may result in the final data being materially different from the interim, initial or preliminary data. We may also experience delays in analyzing or an inability to analyze samples, including, without limitation, biomarker data, due to insufficient sample size, errors in collection procedures at one or more sites, or other factors. As a result, interim, initial or preliminary data should be viewed with caution until the final data are available.  

Negative or inconclusive results of our clinical trials of posenacaftor, dirocaftor or nesolicaftor, any proprietary combination therapy candidates, or any other clinical trials we conduct, could mandate repeated or additional clinical studies. We do not know whether our clinical trials of any product candidate will demonstrate adequate efficacy and safety to result in regulatory approval to market such product candidate. Even if early-stage clinical results are favorable, if later-stage clinical trials (including, without limitation, those for longer duration with greater numbers of patients) do not produce favorable results, our ability to obtain regulatory approval for our product candidates, including posenacaftor, dirocaftor and nesolicaftor, and any proprietary combination therapy candidates, may be adversely impacted.

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Our product candidates may cause adverse effects or have other properties that could delay or prevent their regulatory approval or limit the scope of any approved label or market acceptance.

Undesirable side effects caused by our product candidates could cause us or regulatory authorities to interrupt, delay or halt clinical trials and could result in the denial of regulatory approval by the FDA or other comparable foreign regulatory authorities. It is possible that, during the course of the development of posenacaftor, dirocaftor, nesolicaftor, our proprietary combination therapy candidates, or our other product candidates, results of our studies and clinical trials could reveal an unacceptable severity and prevalence of side effects and/or drug-drug interactions. For example, in preclinical testing of nesolicaftor we observed reduced platelet counts in the animals we tested following administration at doses in excess of the doses we expect to administer in our clinical trials. As a result of this or any other side effects, our clinical trials could be suspended or terminated and the FDA or comparable foreign regulatory authorities could order us to cease further development, or deny approval, of our product candidates for any or all targeted indications. The drug-related side effects could affect patient recruitment or the ability of enrolled patients to complete the trial or result in potential product liability claims or result in delays in the trials due to requirements to provide new informed consents to patients to disclose new or changed risks or side effects.  Even if approved for marketing, our product candidates could face label restrictions based on the above factors or others.

Additionally, if one or more of our product candidates receive marketing approval, and we or others later identify undesirable side effects caused by such products, a number of potentially significant negative consequences could result, including:

regulatory authorities may withdraw approvals of such product or impose restrictions on its distribution in a form of a modified Risk Evaluation and Mitigation Strategy;

regulatory authorities may require additional labeling, such as warnings or contraindications;

we may be required to change the way the product is administered or to conduct additional clinical studies;

we could be sued and held liable for harm caused to patients; and

our reputation may suffer.

Any of these events could delay or prevent us from achieving or maintaining market acceptance of the particular product candidate, if approved, and could significantly harm our business, results of operations and prospects.

If we cannot demonstrate an acceptable safety and toxicity profile for our product candidates in our clinical studies, we will not be able to continue our clinical trials or obtain approval for our product candidates.

In order to obtain approval of a product candidate, we must demonstrate safety in various nonclinical and clinical tests. At the time of initiating human clinical trials, we may not have conducted or may not conduct the types of nonclinical testing ultimately required by regulatory authorities, or future nonclinical tests may indicate that our product candidates are not safe for use. Nonclinical testing and clinical testing are both expensive and time-consuming and have uncertain outcomes. For example, results of an earlier laboratory study of PTI-130, a former amplifier candidate, in non-rodent species suggested potential hematologic and reproductive toxicology issues that we believe are specific to the non-rodent species. We cannot predict whether future safety and toxicology studies may produce these same problems or cause other undesirable effects. We also observed certain undesired hematological (including reduced platelet count) side effects in animals dosed at levels of nesolicaftor that are higher than those intended for our clinical studies. We plan to complete additional toxicity studies of reproductive toxicity, carcinogenicity and long-term side effects prior to or concurrent with any Phase 3 clinical trials of our product candidates, and we cannot exclude the possible occurrence of these or other side effects in future nonclinical or clinical studies. In addition, success in initial tests does not ensure that later testing will be successful. We may experience numerous unforeseen events during, or as a result of, the testing process, which could delay or prevent our ability to develop or commercialize our product candidates, including:

our preclinical and nonclinical testing may produce inconclusive or negative safety results, which may require us to conduct additional nonclinical testing or to abandon product candidates;

our product candidates may have unfavorable pharmacology or toxicity characteristics or suggest possible drug-drug interaction;

our product candidates may cause undesirable side effects; and

the FDA or other regulatory authorities may determine that additional safety testing is required.

Any such events would increase our costs and could delay or prevent our ability to commercialize our product candidates, which could adversely impact our business, financial condition and results of operations.

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Nesolicaftor is based on a novel technology, which may raise development issues we may not be able to resolve, regulatory issues that could delay or prevent approval, or personnel issues that may keep us from being able to develop our product candidates.

Our product candidate nesolicaftor is based on our novel amplifier technology. We are not aware of other drugs that work in a manner that we believe our amplifier technology does. We cannot assure you that development problems related to our novel technology will not arise in the future that could cause significant delays or that we are not able to resolve.

Clinical development and regulatory approval of novel product candidates such as ours can be more expensive and take longer than other, more well-known or extensively studied pharmaceutical product candidates due to our, investigators’ and regulatory agencies’ lack of experience with them. These factors also apply to patient advocacy groups and sanctioning by their affiliated therapeutic development center arms, such as the TDN. To our knowledge, there are no other amplifiers in clinical development and none have been approved to date. The novelty of our technology may lengthen the clinical development timeline and regulatory review process, require us to conduct additional studies or clinical trials, increase our development costs, lead to changes in regulatory positions and interpretations, delay or prevent approval and commercialization of our product candidates or lead to significant post-approval limitations or restrictions. For example, the FDA could require additional studies or characterization that may be difficult or impossible to perform.

In addition, if we are unable to hire and retain the necessary personnel, the rate and success at which we can develop and commercialize product candidates will be limited. Any such events would increase our costs and could delay or prevent our ability to commercialize our product candidates, which could adversely impact our business, financial condition and results of operations.

Even if we meet safety and efficacy endpoints in clinical trials, we cannot predict whether or when we will obtain regulatory approval to commercialize our product candidates and we cannot, therefore, predict the timing of any future revenue from posenacaftor, dirocaftor, nesolicaftor, our proprietary combination therapy candidates or any of our other product candidates.

We cannot commercialize our product candidates, including posenacaftor, dirocaftor, nesolicaftor, and our proprietary combination therapy candidates, until the appropriate regulatory authorities, such as the FDA, have reviewed and approved the product candidate. The regulatory agencies may not complete their review processes in a timely manner, or we may not be able to obtain regulatory approval for posenacaftor, dirocaftor, nesolicaftor, proprietary combination therapy candidates, or our other product candidates at all. Additional delays may result if posenacaftor, dirocaftor, nesolicaftor, proprietary combination therapy candidates, or any other product candidate is brought before an FDA advisory committee or an analogous foreign body, which could recommend restrictions on approval or recommend non-approval of the product candidate. In addition, we may experience delays or rejections based upon additional government regulation from future legislation or administrative action, or changes in regulatory agency policy during the period of product development, clinical studies and the review process. As a result, we cannot predict when, if at all, we will receive any future revenue from commercialization of any of our product candidates, including posenacaftor, dirocaftor, nesolicaftor, and proprietary combination therapy candidates.

Even if we obtain regulatory approval for our proprietary candidates and/or our other product candidates, we will still face extensive regulatory requirements and our products may face future development and regulatory difficulties.

Even if we obtain regulatory approval in the United States, the FDA may still impose significant restrictions on the indicated uses or marketing of our product candidates, including posenacaftor, dirocaftor and nesolicaftor and our proprietary combination therapy candidates, or impose ongoing requirements for potentially costly post-approval studies or post-market surveillance, including Phase 4 clinical trials. For example, the labeling, if approved for our product candidates, including posenacaftor, dirocaftor and nesolicaftor and our proprietary combination therapy candidates, will likely include restrictions on use due to the specific patient population and manner of use in which the drug was evaluated and the safety and efficacy data obtained in those evaluations.  

Posenacaftor, dirocaftor, nesolicaftor, our proprietary combination therapy candidates and our other product candidates will also be subject to additional ongoing FDA requirements governing the labeling, packaging, storage, distribution, safety surveillance, advertising, promotion, record-keeping and reporting of safety and other post-market information. The holder of an approved NDA is obligated to monitor and report adverse events and any failure of a product to meet the specifications described in the NDA. The holder of an approved NDA must also submit new or supplemental applications and obtain FDA approval for certain changes to the approved product, product labeling or manufacturing process. Advertising and promotional materials must comply with FDA rules and are subject to FDA review, in addition to other potentially applicable federal and state laws.

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In addition, manufacturers of drug products and their facilities are subject to payment of user fees and continual review and periodic inspections by the FDA and other regulatory authorities for compliance with current good manufacturing practice, or cGMP, requirements and adherence to commitments made in the NDA. If we, or a regulatory agency, discover previously unknown problems with a product, such as quality issues or adverse events of unanticipated severity or frequency, or problems with the facility where the product is manufactured, a regulatory agency may impose restrictions relative to that product or the manufacturing facility, including requesting a recall or requiring withdrawal of the product from the market or suspension of manufacturing.

If we fail to comply with applicable regulatory requirements following approval of our product candidate, a regulatory agency may:

issue an untitled or warning letter asserting that we are in violation of the law;

seek an injunction or impose civil or criminal penalties or monetary fines;

suspend or withdraw regulatory approval;

suspend any ongoing clinical trials;

refuse to approve a pending NDA or supplements to an NDA submitted by us; or

request a recall and/or seize product.

Any government investigation of alleged violations of law could require us to expend significant time and resources in response and could generate negative publicity. The occurrence of any event or penalty described above may inhibit our ability to commercialize posenacaftor, dirocaftor, nesolicaftor, our proprietary combination therapy candidates and our other product candidates and inhibit our ability to generate revenues.

Even if we obtain regulatory approval for our proprietary candidates or any of our other product candidates in the one geographical area, we may never obtain approval for or commercialize these candidates or any of our other product candidates outside of that area, which would limit our ability to realize their full market potential.

In order to market any products in the United States or European Union, we must establish and comply with numerous and varying regulatory requirements on a country-by-country basis regarding safety and efficacy. Approval by the FDA or EMA does not ensure approval by regulatory authorities in other countries or jurisdictions. In addition, clinical trials conducted in one country may not be accepted by regulatory authorities in other countries, and regulatory approval in one country does not guarantee regulatory approval in any other country. Approval processes vary among countries and can involve additional product testing and validation and additional administrative review periods. Successful approval by one jurisdiction does not necessarily guarantee approval in any other jurisdiction. Further, the disparate impact of COVID-19 across the United States and the European Union could result in yet further differences in their respective regulatory regimes, and an unwillingness for the FDA or EMA to accept data from clinical trials conducted in certain geographies.

Seeking foreign regulatory approval could result in difficulties and costs for us and require additional preclinical studies or clinical trials which could be costly and time consuming. Regulatory requirements can vary widely from country to country and could delay or prevent the introduction of our product candidates in those countries. We do not have any product candidates approved for sale in any jurisdiction, including international markets, and we do not have experience in obtaining regulatory approval in international markets. If we fail to comply with regulatory requirements in international markets or to obtain and maintain required approvals, or if regulatory approvals in international markets are delayed, our target market will be reduced and our ability to realize the full market potential of our product candidates will be unrealized.

If we are not able to obtain or maintain orphan product status for our product candidates for which we seek this status, we will not be able to claim the tax credits for our clinical trials of such products provided by this status or potentially take advantage of other benefits of orphan drug status.

Regulatory authorities in some jurisdictions, including the United States and the European Union, may designate drugs forand biologics intended to treat relatively small patient populations as orphan drugs. Under the Orphan Drug Act of 1983, the FDA may designate a product candidate as an orphan drug if it is a drug intended to treat a rare disease or condition, which is generally defined as a disease or condition thathaving a patient population of fewer than 200,000 individuals in the United States, have been diagnosed as having ator a patient population greater than 200,000 in the timeUnited States where there is no reasonable expectation that the cost of developing the submission ofdrug will be recovered from sales in the requestUnited States. In the European Union, the European Commission after recommendation from the EMA’s Committee for orphan drug designation. Under Regulation No. (EC) 141/2000 on Orphan Medicinal Products a medicinal product may be designated as angrants orphan medicinal product if, among other things, it isdrug designation to promote the development of products that are intended for the diagnosis, prevention or treatment of a life-threatening or chronically debilitating condition affecting not more than five5 in 10,000 peoplepersons in the European Union. Additionally, orphan designation is granted for products intended for the diagnosis, prevention or treatment of a life-threatening, seriously debilitating or serious and chronic condition and when, without incentives, it is unlikely that sales of the drug in the European Union whenwould be sufficient to justify the application is made. necessary investment in developing the drug or biologic product.

If we request orphan drug designation for our product candidates, there can be no assurances that FDA or the European Commission will grant any of our product candidates such designation. Additionally, orphan drug designation does not guarantee that any regulatory authority will accelerate regulatory review of, or ultimately approve, the product candidate, nor does it limit the ability of any regulatory authority to grant orphan drug designation to product candidates of other companies that treat the same indications.

Generally, if a product candidate with an orphan drug designation subsequently receives the first marketing approval for the indication for which it has such designation, the product is entitled to a period of market exclusivity. Thismarketing exclusivity, which precludes the EMAFDA or the FDA, as applicable,European Commission from approving another marketing application for a product that constitutes the same or, in the European Union, a similar drug fortreating the same indication for that timemarketing exclusivity period, unless, among other things,except in limited circumstances. If another sponsor receives such approval before we do (regardless of our orphan drug designation), we will be precluded from receiving marketing approval for our product for the later product is clinically superior.applicable exclusivity period. The exclusivityapplicable period is seven years in the United States and ten10 years in the European Union following marketing approval.Union. The EU exclusivity period in the European Union can be reduced to

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six years if a drugproduct no longer meets the criteria for orphan drug designation for exampleor if the drugproduct is sufficiently profitable so that market exclusivity is no longer justified. Orphan drug exclusivity may be revoked if any regulatory authority determines that the request for designation was materially defective or if the manufacturer is unable to assure sufficient quantity of the product to meet the needs of patients with the rare disease or condition.

Even if we obtain orphan drug exclusivity for a product candidate, that exclusivity may not effectively protect the product candidate from competition because different drugs can be approved for the same condition. In the United States, orphan drug exclusivity may be lost if the FDA withdraws or revokes the orphan-drug designation as permitted by law, we withdraw the marketing application for the drug, we consent to another’s marketing application for approval of the same use or indication as the designated orphan drug, or we fail to assure a sufficient quantity of the drug as required by law. Similarly, in the European Union, exclusivity may be lost if we request the removal of the orphan-drug designation or the drug no longer meets any of the criteria that made it eligible for orphan-drug status at the outset. Eveneven after an orphan drug is approved, the same or, in the European Union, a similarFDA may subsequently approve another drug can subsequently be approved for the same condition if the competent regulatory agencyFDA concludes that the laterlatter drug is not the same drug or is clinically superior in that it is shown to be safer, more effective or makes a major contribution to patient care.

We are currently, and may in the original orphan drug by providing a significant therapeutic advantage over and above that drug.

If we do not obtain orphan drug exclusivity or if our competitors obtain orphan drug exclusivityfuture, conduct clinical trials for other rare diseases or conditions we are targeting before we do, we may be delayed in obtaining marketing authorization or we may lose out on the potential benefits of market exclusivity associated with the orphan drug designation. Among the other benefits of orphan drug designation are tax credits for certain research and a waiver of the NDA application user fee. If we do not obtain orphan designation for posenacaftor or our other product candidates (and maintain such designation as to nesolicaftor), we will lose out on such benefits associated with orphan designation.

Use of social media platforms presents new risks.

Social media increasingly is being used to communicate about our product candidates outside the United States, and the diseases our therapiesFDA and similar foreign regulatory authorities may not accept data from such trials.

We are designedcurrently, and may in the future, conduct additional clinical trials outside the United States, including in Europe or other foreign jurisdictions. The acceptance of trial data from clinical trials conducted outside the United States by the FDA may be subject to treat. We believe that memberscertain conditions. In cases where data from clinical trials conducted outside the United States are intended to serve as the sole basis for marketing approval in the United States, the FDA will generally not approve the application on the basis of foreign data alone unless (i) the data are applicable to the United States population and United States medical practice; (ii) the trials were performed by clinical investigators of recognized competence; and (iii) the data may be considered valid without the need for an on-site inspection by the FDA or, if the FDA considers such an inspection to be necessary, the FDA is able to validate the data through an on-site inspection or other appropriate means. Additionally, the FDA’s clinical trial requirements, including sufficient size of patient populations and statistical powering, must be met. Many foreign regulatory bodies have similar approval requirements. In addition, such foreign trials would be subject to the applicable local laws of the CF community mayforeign jurisdictions where the trials are conducted. There can be more active on social media as compared to other patient populations. Social media practicesno assurance that the FDA or any similar foreign regulatory authority will accept data from trials conducted outside of the United States or the applicable jurisdiction. If the FDA or any similar foreign regulatory authority does not accept such data, it would result in the pharmaceuticalneed for additional trials, which would be costly and biotechnology industries are evolving,time-consuming and delay aspects of our business plan, and which creates uncertaintymay result in our product candidates not receiving approval for commercialization in the applicable jurisdiction.

Changes in regulatory requirements, FDA guidance, or unanticipated events during our preclinical studies and riskclinical trials of noncompliance with regulations applicableour product candidates may occur, which may result in changes to our business. For example, patients may use social media platforms to comment on the effectiveness of,preclinical or adverse experiences with, a drug candidate,clinical study protocols or additional preclinical or clinical study requirements, which could result in reporting obligations. In addition, there is a risk of inappropriate disclosure of sensitive informationincreased costs to us and could delay our development timeline.

Changes in regulatory requirements, FDA guidance, or negativeunanticipated events during our preclinical studies and clinical trials may force us to amend preclinical studies and clinical trial protocols or inaccurate poststhe FDA may impose additional preclinical studies and clinical trial requirements. Amendments or comments about us on any social networking website. If any of these events were to occur or we otherwise fail to comply with applicable regulations, we could incur liability, face restrictive regulatory actions or incur other harmchanges to our business.

Risks Relatedclinical study protocols would require resubmission to Our Dependence on Third Parties

the FDA and IRBs for review and approval, which may adversely impact the cost, timing, or successful completion of clinical trials. Similarly, amendments to our preclinical studies may adversely impact the cost, timing, or successful completion of those preclinical studies. If third parties on which we depend to conductexperiences delays completing, or if we terminate, any of our preclinical studies or any ongoing or future clinical trials, do not perform as contractually required, fail to satisfy regulatory or legal requirements or miss expected deadlines, our development program could be delayed with materially adverse effects on our business and prospects.

We rely on clinical research organizations, clinical data management organizations and consultants, collectively referred to as CROs, to design, conduct, supervise and monitor preclinical and clinical studies of our product candidates and plan to do the same for our ongoing and future clinical trials for posenacaftor, dirocaftor, nesolicaftor, proprietary combination therapy candidates and any other clinical trials. We and our CROsif we are required to comply with various regulations, including Good Clinical Practice,conduct additional preclinical studies or GCP, requirements, which are enforced by the FDA, and guidelines of the Competent Authorities of the Member States of the European Economic Area, and comparable foreign regulatory authorities to ensure that the health, safety and rights of patients are protected in clinical development and clinical trials, and that trial data integrity is assured. Regulatory authorities ensure compliance with these requirements through periodic inspections of trial sponsors, principal investigators and trial sites, as well as third party contractors. If we or any of our CROs fail to comply with applicable requirements, or the CRO does not perform its contractually required obligations (or makes errors or mistakes), the clinical data, including, without limitation, biomarker data, generated in our clinical trials may not be collected or may be collected but be deemed unreliable, and the FDA, the EMA or other comparable foreign regulatory authorities may require us (or we may choose ourselves) to perform additional clinical trials before approving our marketing applications. We cannot assure you that upon inspection by a given regulatory authority, such regulatory authority will determine that any of our clinical trials comply with such requirements. In addition, our clinical trials must be conducted with products produced under cGMP requirements, which mandate the methods, facilities and controls used in manufacturing, processing and packaging of a drug product to ensure its safety and identity. Failure to comply with these regulations may require us to delay or repeat preclinical and clinical trials, which would delay the regulatory approval process.

Our CROs are not our employees, and except for remedies available to us under our agreements with such CROs, we cannot control whether or not they devote sufficient time and resources to our ongoing clinical and preclinical programs. We generally represent a small percentage of these firms’ overall business, which could limit our ability to receive priority allocation of their resources. If CROs do not successfully carry out their contractual duties or obligations or meet expected deadlines or if the quality or accuracy of the clinical data they obtain is compromised due to the failure to adhere to our clinical protocols, regulatory requirements or for other reasons, our clinical trials may be extended, delayed or terminated and we may not be able to obtain regulatory approval for or successfully commercialize our product candidates. As a result, our operations and the commercial prospects for our product candidates wouldmay be harmed our costs could increase and our ability to generate revenues couldproduct revenue will be delayed.

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We also rely on clinical investigators and clinical research organizations, as well as therapeutics development arms of patient advocacy groups, such as the HIT-CF, TDN and CTN, to assistIf, in the design and review of our clinical trials, including supporting the enrollment of qualified patients.  If these third parties do not approve or sanction our trial protocols to facilitate enrollment, our ability to conduct clinical trials may be impeded.  Because we have relied on third parties, our internal capacity to perform these functions is limited. Outsourcing these functions involves risk that third parties may not perform to our standards, may not produce results in a timely manner or may fail to perform at all. In addition, the use of third-party service providers requires us to disclose our proprietary information to these parties, which could increase the risk that this information will be misappropriated or inadvertently be made publicly-available. We currently have a small number of employees, which limits the internal resources we have available to identify and monitor our third-party providers. To the extent we are unable to identify and successfully manage the performance of third-party service providers in the future, our business may be adversely affected. Though we carefully manage our relationships with our CROs, and other third parties, there can be no assurance that we will not encounter similar challenges or delays in the future or that these delays or challenges will not have a material adverse impact on our business, financial condition and prospects.

In addition, our CROs and collaborators have been and may continue to be affected by the COVID-19 pandemic. Clinical site closure and other activities that require visits to clinical sites, have been and may continue to be delayed due to prioritization of hospital resources toward the COVID-19 pandemic or concerns among patients about participating in clinical trials during a pandemic. This is particularly true of our European-based collaborators, in which we are aware of certain disruptions and potential delays in ex vivo in testing of organoids due to the research personal transitioning to working in shifts to reduce the number of people gathered together at one time in any given laboratory or temporary closures of research laboratories. Disruption of our collaborators’ and CRO’s business as a result of COVID-19 could increase the likelihood that they are unable to perform as contractually required, which could have a material adverse effect on our business, financial condition, results of operations and prospects.

If we cannot contract with acceptable third parties on commercially reasonable terms, or at all, or if these third parties do not carry out their contractual duties, satisfy legal and regulatory requirements for the conduct of preclinical studies or clinical trials or meet expected deadlines, our clinical development programs could be delayed and otherwise adversely affected. In all events, we are responsible for ensuring that each of our preclinical studies and clinical trials is conducted in accordance with the general investigational plan and protocols for the trial. The FDA and the EMA require clinical trials to be conducted in accordance with GCP, including for conducting, recording and reporting the results of preclinical studies and clinical trials to assure that data and reported results are credible and accurate and that the rights, integrity and confidentiality of clinical trial participants are protected. Our reliance on third parties that we do not control does not relieve us of these responsibilities and requirements. Any such event could have a material adverse effect on our business, financial condition, results of operations and prospects.

We rely on third-party manufacturers and suppliers and we intend to rely on third parties to produce preclinical, clinical and commercial supplies of posenacaftor, dirocaftor, nesolicaftor and any future product candidates. These third parties may not perform as contractually required or expected and issues may arise that could delay the commencement or completion of clinical trials.

We rely on third parties to supply the materials and components for our research and development, preclinical and clinical trial supplies. We do not own manufacturing facilities or supply sources for such components and materials. There can be no assurance that our supply of research and development, preclinical and clinical development drugs and other materials will not be limited, interrupted, restricted in certain geographic regions or of satisfactory quality or continue to be available at acceptable prices. Any replacement of these third parties could require significant effort and expertise because there may be a limited number of qualified replacements.

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The manufacturing process for a product candidate is subject to FDA, EMA and other foreign regulatory authority review. Suppliers and manufacturers must meet applicable manufacturing requirements and undergo rigorous facility and process validation tests required by regulatory authorities to comply with regulatory standards such as cGMP. In the event that any of our suppliers or manufacturers fails to comply with such requirements or to perform its obligations to us in relation to quality, timing or otherwise, or if our supply of components or other materials becomes limited or interrupted for other reasons, our regulatory filings may be delayed, our preclinical studies or clinical trials may be delayed or suspended, and we may be forced to manufacture the materials ourselves, for which we currently do not have the capabilities or resources, or enter into an agreement with another third party, which we may not be able to do on reasonable terms, if at all. In some cases, the technical skills or technology required to manufacture our product candidates may be unique or proprietary to the original manufacturer and we may have difficulty, or there may be contractual restrictions prohibiting us from, transferring such skills or technology to another third party and a feasible alternative may not exist; even if it exists, it may be cost-prohibitive and time-prohibitive to engage in technology transfer to switch vendors for drug substance and/or product candidate manufacturing. These factors would increase our reliance on such manufacturer or require us to obtain a license from such manufacturer in order to have another third party manufacture our drug substance and/or product candidates. If we are required to change manufacturers for any reason, we will be required to verify that the new manufacturer maintains facilities and procedures that comply with quality standards and with all applicable regulations and guidelines. The delays associated with the verification of a new manufacturer could negatively affect our ability to develop product candidates in a timely manner or within budget.  Drug formulation is an inherently uncertain process with numerous steps, some of which may need to be repeated, to ensure quality, accuracy and yield; unexpected variances may occur, which could delay our manufacturing efforts and delay commencement or completion of preclinical studies and/or clinical trials.

Additionally, our third-party manufacturers and suppliers have been impacted and may continue to be impacted by the COVID-19 pandemic. We depend on personnel at third-party manufacturing facilities in the United States and other countries to manufacture products used in our preclinical studies and clinical trials. Quarantines, shelter-in-place and similar government orders, or the expectation that such orders, shutdowns or other restrictions could occur, whether related to COVID-19 or other infectious diseases, could impact personnel at third-party manufacturing facilities in the United States, European Union and other countries, or the availability or cost of materials, which could disrupt our supply chain.

If our relationships with our manufacturers, suppliers or other vendors are terminated or scaled back as a result of the COVID-19 pandemic or other health epidemics, we may not be able to enter into arrangements with alternative suppliers or vendors or do so on commercially reasonable terms or in a timely manner. Further, if the COVID-19 pandemic persists for an extended period of time and begins to impact essential distribution systems such as FedEx and postal delivery, we could experience disruptions to our supply chain and operations, and associated delays in the manufacturing and supply of our product candidates. Switching or adding additional suppliers or vendors involves substantial cost and requires management time and focus. In addition, there is a natural transition period when a new supplier or vendor commences work. As a result, delays may occur, which could adversely impact our ability to meet our desired clinical development and any future commercialization timelines. Although we carefully manage our relationships with our suppliers and vendors, there can be no assurance that we will not encounter challenges or delays in the future or that these delays or challenges will not harm our business.

We expect to continue to rely on third-party manufacturers if we receive regulatory approval for any product candidate. To the extent that we have existing, or enter into future, manufacturing arrangements with third parties, we will depend on these third parties to perform their obligations in a timely manner consistent with contractual and regulatory requirements, including those related to quality control and assurance. If we are unable to obtain or maintain third-party manufacturing for product candidates, or to do so on commercially reasonable terms, we may not be able to develop and commercialize our product candidates successfully. Our or a third party’s failure to execute on our manufacturing requirements could adversely affect our business in a number of ways, including:

preventing us from initiating or continuing preclinical studies or clinical trials of product candidates under development;

delaying our trials and/or delaying submissions of regulatory applications or receipt of regulatory approvals for product candidates;

preventing a collaborator from cooperating with us;

subjecting our product candidates to additional inspections by regulatory authorities;

requiring us to cease distribution or to recall batches of our product candidates; and

in the event of approval to market and commercialize a product candidate, preventing us from meeting commercial demands for our products.

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If a current or future collaborative partner terminates or fails to perform its obligations under an agreement with us, or if research does not produce viable lead candidates or meet specified criteria during the applicable research term, the development and commercialization of the product candidates could be delayed or terminated.

If one of our collaborative partners, such as Genentech, does not devote sufficient time and resources to a collaboration arrangement with us, we may not realize the potential commercial benefits of the arrangement, and our results of operations may be materially adversely affected.

Much of the potential revenue from our collaboration consists of contingent payments, such as payments for achieving scientific or regulatory milestones or royalties payable on sales of drugs. The milestone and royalty revenue that we may receive under collaborations will depend upon our collaborators’ ability to successfully develop, introduce, market and sell new products. Our collaboration partners may fail to develop or effectively commercialize their products using our products or technologies or otherwise discontinue their research activities because they:

exercise their unilateral right to terminate the collaboration agreement including, without limitation, if research does not produce a viable lead candidate or meet specified criteria during the applicable research term;

decide not to devote the necessary resources due to internal constraints, such as limited personnel with the requisite expertise, limited cash resources or specialized equipment limitations, or the belief that other drug development programs may have a higher likelihood of obtaining marketing approval or may potentially generate a greater return on investment;

decide to pursue other technologies or develop other product candidates, either on their own or in collaboration with others, including our competitors, to treat the same diseases targeted by our own collaborative programs;

do not have sufficient resources necessary to carry the product candidate through clinical development, marketing approval and commercialization; or

cannot obtain the necessary marketing approvals.

Competition may negatively impact a partner’s focus on and commitment to our relationship and, as a result, could delay or otherwise negatively affect the commercialization of our products, which would have a material adverse effect on our operating results and financial condition. Terminated collaborations include the risk that the former partner maintains rights to exploit certain co-developed technology, and the risk that, to the extent the program is desired to continue, funding formerly provided by the partner will need to come from alternative sources such as us or a new partner and such funding may not be available on terms acceptable to us, if at all.  These factors can cause a delay or abandonment of technology programs and could negatively affect commercialization of our products, which would have a material adverse effect on our operating results and financial condition.

We face a number of challenges in seeking future collaborations. Collaborations are complex and any potential discussions may not result in a definitive agreement for many reasons. For example, whether we reach a definitive agreement for a collaboration will depend, among other things, upon our assessment of the collaborator’s resources and expertise, the terms and conditions of the proposed collaboration, and the proposed collaborator’s evaluation of a number of factors, such as the design or results of our clinical trials, the potential market for our product candidates, the costs and complexities of manufacturing and delivering our product candidates to patients, the potential of competing products, the existence of uncertainty with respect to ownership or the coverage of our intellectual property, and industry and market conditions generally. If we determine that additional collaborations for our product candidates are necessary and are unable to enter into such collaborations on acceptable terms, we might elect to delay or scale back the development or commercialization of our product candidates in order to preserve our financial resources or to allow us adequate time to develop the required physical resources and systems and expertise ourselves.

Collaboration agreements may not lead to development or commercialization of product candidates in the most efficient manner, or at all. In addition, there have been a significant number of recent business combinations among large pharmaceutical companies that have resulted in a reduced number of potential future collaborators. If a current or future collaborator of ours were to be involved in a business combination, the continued pursuit and emphasis on our product development or commercialization program could be delayed, diminished or terminated.

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Risks Related to Commercialization of Our Product Candidates

The commercial success of posenacaftor, dirocaftor, nesolicaftor, any proprietary combination therapy candidates and our other product candidates will depend upon the acceptance of those products, if approved, by the medical community, including physicians, patients and health care payors.

Even if posenacaftor, dirocaftor, nesolicaftor, any proprietary combination therapy candidates or our other product candidates are approved for sale, they may not achieve sufficient market acceptance by physicians, patients, healthcare payors and others in the medical community. If these product candidates, if approved, do not achieve an adequate level of acceptance, we may not generate significant product revenues and we may not become profitable. The degree of market acceptance of any of our product candidates, including posenacaftor, dirocaftor and nesolicaftor and any proprietary combination therapy candidates, will depend on a number of factors, including:

demonstration of safety and efficacy in our clinical trials and in any post-marketing studies;

the relative convenience, ease of administration and acceptance by physicians, patients and health care payors;

the prevalence and severity of any adverse effects;

limitations or warnings contained in the FDA-approved label for the relevant product candidate;

availability of alternative treatments;

pricing and cost-effectiveness;

the effectiveness of our or any future collaborators’ sales and marketing strategies; and

our ability to obtain and maintain healthcare payor approval and reimbursement, which may vary from country to country and within a country.

If any of our product candidates, including posenacaftor, dirocaftor and nesolicaftor and any proprietary combination therapy candidates, is approved but does not achieve an adequate level of acceptance by physicians, patients and health care payors, we may not generate sufficient revenue and we may not become or remain profitable.

If we are unable to establish sales and marketing capabilities or enter into agreements with third parties to sell and market ourany product candidates we may develop, we may not be successful in commercializing ourthose product candidates if and when they are approved.

We do not currently have a sales or marketingan infrastructure and we have limited experience infor the sales, marketing, orand distribution of pharmaceutical products. Our commercialization strategy will target key prescribing physicians and advocacy groups, as well as provide patients with support programs, and seekIn order to ensure product access and secure reimbursement. Outside of the United States, Canada, Europe and Australia, we may seek a partner to commercialize our products. In the future, we may choose to build a focused sales and marketing infrastructure to market or co-promote our product candidates, if approved by the FDA or any other regulatory body, we must build our sales, marketing, managerial, and when theyother non-technical capabilities, or make arrangements with third parties to perform these services. There are approved, which would be expensiverisks involved with both establishing our own commercial capabilities and time-consuming. Alternatively, we may electentering into arrangements with third parties to outsourceperform these functions to third parties. Either approach carries significant risks.services. For example, recruiting and training a sales force or reimbursement specialists is expensive and time-consuming and if done improperly, could delay aany product launch and result in limited sales.launch. If the commercial launch of a product candidate for which we recruit a sales force and establish marketing and other commercialization capabilities is delayed or does not occur for any reason, we would have prematurely or unnecessarily incurred these commercialization expenses. This may be costly, and our investment would be lost if we cannot retain or reposition our sales and marketingcommercialization personnel.

Factors that may inhibit our efforts to commercialize our product candidates on our own include:

inability to recruit, manage and retain adequate numbers of effective sales and marketing personnel;

the inability of marketing personnel to develop effective marketing materials;

the inability of sales personnel to obtain access to or persuade adequate numbers of physicians to prescribe any future products;

the lack of complementary products to be offered by sales personnel, which may put us at a competitive disadvantage relative to companies with more extensive product lines; and

unforeseen costs and expenses associated with creating an independent sales and marketing organization.

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We may also not be successful in entering into additional arrangements with third parties to sell and market our product candidates or doing so on terms that are favorable to us. Even ifIf we do enter into arrangements with third parties to perform sales, marketing, commercial support, and distribution services, our product revenuesrevenue or the profitability of these product candidates are likely torevenue may be lower than if we were to market and sell ourany products we may develop ourselves. In addition, we likely willmay not be successful in entering into arrangements with third parties to commercialize our product candidates or may be unable to do so on terms that are favorable to us. We may have little control over such third parties, and any of them may fail to devote the necessary resources and attention to sell and market our products effectively. If we dodoes not establish sales and marketingcommercialization capabilities successfully, either on our own or in collaboration with third parties, we will not be successful in commercializing our product candidates.candidates if approved.

If we are unable to establish adequate sales, marketing, and distribution capabilities, whether independently or with third parties, or if we are unable to do so on commercially reasonable terms, our competitors develop technologies or product candidates more rapidly than we do or their technologies are more effective, our ability to developbusiness, results of operations, financial condition, and successfully commercialize our products mayprospects will be materially adversely affected. Competitive products for treatment of CF may reduce or eliminate the commercial opportunity

Even if we receive marketing approval for our product candidates.candidates, our product candidates may not achieve broad market acceptance by physicians, patients, healthcare payors, or others in the medical community, which would limit the revenue that we generate from their sales.

The clinical and commercial landscape for CF is highly competitive and subject to rapid and significant technological change. New data from clinical-stage products continue to emerge. It is possible that these data may alter the current standardsuccess of care, completely precluding us from further developing posenacaftor, dirocaftor, nesolicaftor, our proprietary combination therapy candidates or our other product candidates, for CF. Further, it is possible that we may advanceif approved by the FDA or other applicable regulatory authorities, will depend upon the awareness and acceptance of our clinical trials only to find that data from competing products make it impossible for us to complete enrollment in these trials, resulting inproduct candidates among the medical community, including physicians, patients, and healthcare payors. If any of our inability to file for marketing approval with regulatory agencies. Even if posenacaftor, dirocaftor, nesolicaftor, proprietary combination therapy candidates or our other product candidates are approved but do not achieve an adequate level of acceptance by physicians, patients, healthcare payors, and others in the medical community, we may not generate sufficient revenue to become or remain profitable. Market acceptance of our product candidates, if approved, will depend on a number of factors, including, among others:

the safety, efficacy, and other potential advantages of our approved product candidates compared to other available therapies;

limitations or warnings contained in the labeling approved for our product candidates by the FDA or other applicable regulatory authorities;

any restrictions on the use of our products together with other medications;

the prevalence and severity of any adverse effects associated with our products;

inability of certain types of patients to take our products;

the clinical indications for which our product candidates are approved;

availability of alternative treatments already approved or expected to be commercially launched in the near future;

the potential and perceived advantages of our approved product candidates over current treatment options or alternative treatments, including future alternative treatments;

the size of the target patient population, and the willingness of the target patient population to try new therapies and of physicians to prescribe these therapies;

the strength of marketing theyand distribution support and timing of market introduction of competitive products;

publicity concerning our products or competing products and treatments;

pricing and cost effectiveness;

the effectiveness of our sales and marketing strategies;

our ability to increase awareness of our products through sales and marketing efforts;

our ability to obtain sufficient third-party payor coverage or reimbursement; or

the willingness of patients to pay out-of-pocket in the absence of third-party payor coverage.

If our product candidates are approved but do not achieve an adequate level of acceptance by patients, physicians, and payors, we may have limited sales duenot generate sufficient revenue from our approved product candidates to particularly intensebecome or remain profitable. Before granting reimbursement approval, healthcare payors may require us to demonstrate that our product candidates, in addition to treating these target indications, also provide incremental health benefits to patients. Our efforts to educate the medical community and third-party payors about the benefits of our product candidates may require significant resources and may never be successful.

We face significant competition in the CF market.

Competitive therapeutic treatments include thosean environment of rapid technological and scientific change, and there is a possibility that our competitors may achieve regulatory approval before we do or develop therapies that are currently insafer, more advanced, or more effective, which may negatively impact our ability to successfully market or commercialize any product candidates we may develop and ultimately harm our financial condition.

The development and commercialization of new drug products is highly competitive. Moreover, the neurodegenerative field is characterized by strong and increasing competition, with a strong emphasis on intellectual property. We may face competition with respect to any new treatmentsproduct candidates that enter the market. We believe that a significant number of products are currently under development, and may become commercially availablewe seek to develop or commercialize in the future from major pharmaceutical companies, specialty pharmaceutical companies, and biotechnology companies worldwide. Potential competitors also include academic institutions, government agencies, and other public and private research organizations that conduct research, seek patent protection, and establish collaborative arrangements for the treatmentresearch, development, manufacturing, and commercialization.

There are a number of conditions for which we may try to develop product candidates. Our potential competitors include large pharmaceutical and biotechnology companies specialtythat are currently pursuing the development of products for the treatment of the neurodegenerative disease indications for which we have research programs, including Parkinson’s disease, ALS and Alzheimer’s disease. Companies that we are aware of are developing therapeutics in the neurodegenerative disease area include large companies with significant financial resources, such as AbbVie, AstraZeneca, Biogen, Bristol-Myers Squibb, Lilly, GlaxoSmithKline, Johnson & Johnson, Novartis, Roche, Sanofi, and Takeda. In addition to competition from other companies targeting neurodegenerative indications, any products we may develop may also face competition from other types of therapies, such as gene-editing therapies.

Many of our current or potential competitors, either alone or with their strategic partners, have significantly greater financial resources and expertise in research and development, manufacturing, preclinical testing, conducting clinical trials, obtaining regulatory approvals, and marketing approved products than we do. Mergers and acquisitions in the pharmaceutical and generic drugbiotechnology industries may result in even more resources being concentrated among a smaller number of our competitors. Smaller or early-stage companies academic institutions, government agenciesmay also prove to be significant competitors, particularly through collaborative arrangements with large and research institutions. Examples include Vertex Pharmaceuticals Incorporated, AbbVie Inc., F. Hoffmann-LaRoche Ltd., Novartis AG, Gilead Sciences, Inc., Laurent Pharmaceuticals Inc., Pfizer Inc., AstraZeneca, Translate Bio Inc., Sanofi Genzyme, Bayer AG, Corbus Pharmaceuticals Holdings, Inc., Eloxx Pharmaceuticals, Verona Pharma plc, Spirovant Sciences, Enterprise Therapeutics Ltd.established companies. These competitors also compete with us in recruiting and several other companies.

Vertexretaining qualified scientific and management personnel and establishing clinical study sites and patient registration for clinical trials, as well as in acquiring technologies complementary to, or other competitors could develop other drugs or combinations that may obviate the applicability of posenacaftor, dirocaftor and nesolicaftor. Changes in standard of care or use patterns could also make our combination therapy obsolete. For example, Vertex has developed tezacaftor and ivacaftor as a combination therapy on its own, and with another corrector, elexacaftor, and was recently granted marketing approval for both combinations under the names Symdeko and Trikafta, respectively. Also, if gene therapy is able to successfully cure CF, the clinical neednecessary for, our product candidates would diminish.

programs. Our commercial opportunity could be reduced or eliminated if our competitors develop and commercialize products that are safer, more effective, have fewer or less severe side effects, are more convenient, or are less expensive than any products that we may develop. Furthermore, currently approved products could be discovered to have application for treatment of neurodegenerative disease indications, which could give such products significant regulatory and market timing advantages over any of our product candidates. Our competitors also may obtain FDA or other regulatory approval for their products more rapidly than we may obtain approval for ours,our product candidates and may obtain orphan product exclusivity from the FDA for indications our product candidates are targeting, which could result in our competitors establishing a strong market position before we are able to enter the market. In addition, our ability to compete may be affected in many casesAdditionally, products or technologies developed by insurers or other third-party payors seeking to encourage the use of generic products.

Many of our competitors have greater financial, technical, manufacturing, clinical development, marketing, sales and supply resources, technical and human resources or experience than us and significantly greater experience in the discovery and development of product candidates, obtaining FDA and other regulatory approvals of product candidates and the commercialization of those products. Accordingly, our competitors may be more successful thanrender our potential product candidates uneconomical or obsolete, and we may not be successful in obtaining FDA andmarketing any product candidates we may develop against competitors.

In addition, we could face litigation or other regulatory approvals for therapies and achieving widespread market acceptance. Ourproceedings with respect to the scope, ownership, validity and/or enforceability of our patents relating to our competitors’ products and our competitors may be more effective,allege that our products infringe, misappropriate, or more effectively marketedotherwise violate their intellectual property. The availability of our competitors’ products could limit the demand, and sold, thanthe price we are able to charge, for any product candidateproducts that we may commercializedevelop and may rendercommercialize. See “Risks Related to Our Intellectual Property Rights.”

The current pandemic of COVID-19 and the future outbreak of other highly infectious or contagious diseases could seriously harm our therapies obsolete or non-competitive before we can recoverresearch, development and potential future commercialization expenses.efforts, increase our costs and expenses and have a material adverse effect on our business, financial condition and results of operations.

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If we successfully obtain approval for any product candidate, we will face competition based on many different factors,Broad-based business or economic disruptions could adversely affect our ongoing or planned research and development activities. For example, in December 2019, an outbreak of a novel strain of coronavirus originated in Wuhan, China, and has since spread to a number of other countries, including the efficacy, safetyUnited States. To date, the COVID-19 pandemic has caused significant disruptions to the U.S. and tolerabilityglobal economy and has contributed to significant volatility and negative pressure in financial markets. The global impact of our products, the easeoutbreak is continually evolving and, as additional cases of the virus are identified, many countries, including the U.S., have reacted by instituting quarantines, restrictions on travel and mandatory closures of businesses. Certain states and cities, including where we or the third parties with which our products can be administered,whom we engage operate, have also reacted by instituting quarantines, restrictions on travel, “shelter in place” rules, restrictions on types of business that may continue to operate, and/or restrictions on the types of construction projects that may continue.

The extent to which physicians and patients accept combination therapies and, for nesolicaftor, new classes of modulators, the timing and scope of regulatory approvals for these products, the availability and cost of manufacturing, marketing and sales capabilities, price, reimbursement coverage and patent position. Competing products could present superior treatment alternatives, including being more effective, safer, or less expensive, or could be marketed and sold more effectively than any products weCOVID-19 may develop. Competitive products may make any products we develop, or products with which we are approved for use in combination, obsolete or noncompetitive before we recover the expense of developing and commercializing our product candidates. Such competitors could also recruit our employees, which could negatively impact our levelpreclinical studies or clinical trial operations will depend on future developments, which are highly uncertain and cannot be predicted with confidence, such as the duration of expertisethe outbreak, the severity of COVID-19, or the effectiveness of actions to contain and treat COVID-19. The continued spread of COVID-19 globally could adversely impact our ability to execute our business plan. Mergers and acquisitionspreclinical studies or clinical trial operations in the pharmaceutical and biotechnology industries may result in even more resources being concentrated among a small number of competitors.

We also compete with other clinical-stage companies and institutions for clinical trial participants, which could reduceUnited States, including our ability to recruit participants forand retain patients and principal investigators and site staff who, as healthcare providers, may have heightened exposure to COVID-19 if an outbreak occurs in their geography. COVID-19 may also affect employees of third-party CROs located in affected geographies that we rely upon to carry out our clinical trials. For example, actualAny negative impact COVID-19 has to patient enrollment or perceived riskstreatment or the execution of our current product candidates such as posenacaftor, dirocaftor, nesolicaftor, or our proprietary combination therapy candidates, or actual or perceived benefits ofand any future product candidates of our competitors, may negatively affect potentialcould cause costly delays to clinical trial participants or patients when deciding whether to participate in our clinical trials, and could result in patients seeking alternative clinical trials or commercial therapies from our competitors. Delay in recruiting clinical trial participantsactivities, which could adversely affect our ability to bringobtain regulatory approval for and to commercialize our current product candidate and any future product candidates, increase our operating expenses, and have a material adverse effect on our financial results.

Further, the COVID-19 outbreak caused delays in our Phase 1 single ascending dose trial of YTX-7739 and may cause delays in our other clinical trials, including delays in enrollment, due to diversion or prioritization of trial site resources away from the conduct of clinical trials and toward the COVID-19 pandemic. Key clinical trial activities, such as site monitoring, may be interrupted due to restrictions in travel, and some patients may be unwilling to enroll in our trials or be unable to comply with clinical trial protocols if quarantines or travel restrictions impede patient movement or interrupt healthcare services, which would delay our ability to conduct clinical trials or release clinical trial results. The spread of COVID-19, or another infectious disease, could also negatively affect the operations at our third-party manufacturers, which could result in delays or disruptions in the supply of our current product candidates and any future product candidates. In addition, we may take temporary precautionary measures intended to help minimize the risk of the virus to our employees, including temporarily requiring all employees to work remotely, suspending all non-essential travel worldwide for our employees, and discouraging employee attendance at industry events and in-person work-related meetings, which could negatively affect our business.

We cannot presently predict the scope and severity of any potential business shutdowns or disruptions. If we or any of the third parties with whom we engage, however, were to experience shutdowns or other business disruptions, our ability to conduct our business in the manner and on the timelines presently planned could be materially and negatively affected, which could have a material adverse impact on our business and our results of operation and financial condition.

Risks Related to Our Regulatory Approval and Other Legal Compliance Matters

The regulatory approval processes of the FDA and comparable foreign regulatory authorities are lengthy, time-consuming, and inherently unpredictable. If we are ultimately unable to obtain regulatory approval for our product candidates, we will be unable to generate product revenue and our business will be substantially harmed.

The time required to obtain approval by the FDA and comparable foreign regulatory authorities is unpredictable, typically takes many years following the commencement of clinical trials, and depends upon numerous factors, including the type, complexity, and novelty of the product candidates involved. In addition, approval policies, regulations, or the type and amount of clinical data necessary to gain approval may change during the course of a product candidate’s clinical development and may vary among jurisdictions, which may cause delays in the approval or the decision not to market. Further, researchapprove an application. Regulatory authorities have substantial discretion in the approval process and discoveries by othersmay refuse to accept any application or may decide that our data are insufficient for approval and require additional preclinical, clinical or other studies. We have not submitted for, or obtained regulatory approval for any product candidate, and it is possible that none of our existing product candidates or any product candidates we may seek to develop in the future will ever obtain regulatory approval.

Applications for our product candidates could be delayed in receiving or fail to receive regulatory approval for many reasons, including but not limited to the following:

the FDA or comparable foreign regulatory authorities may disagree with the design, implementation, or results of our clinical trials;

the FDA or comparable foreign regulatory authorities may determine that our product candidates are not safe and effective for the proposed indication, or have undesirable or unintended side effects, toxicities, or other characteristics that preclude us obtaining marketing approval or prevent or limit commercial use;

the population studied in the clinical program may not be sufficiently broad or representative to assure efficacy and safety in the full population for which we seek approval;

the FDA or comparable foreign regulatory authorities may disagree with our interpretation of data from preclinical studies or clinical trials;

the data collected from clinical trials of our product candidates may not be sufficient to support the submission of an NDA or other submission, or to obtain regulatory approval in the United States or elsewhere;

we may be unable to demonstrate to the FDA or comparable foreign regulatory authorities that a product candidate’s risk-benefit ratio for our proposed indication is acceptable;

the FDA or comparable foreign regulatory authorities may find deficiencies with or fail to approve the manufacturing processes, test procedures and specifications, or facilities of third-party manufacturers with which we contract for clinical and commercial supplies; and

the approval policies or regulations of the FDA or comparable foreign regulatory authorities may significantly change in a manner rendering our clinical data insufficient for approval.

This lengthy approval process, as well as the unpredictability of the results of clinical trials, may result in breakthroughs that render our product candidates obsolete even before they beginfailing to generate any revenue.

In addition, our competitors may obtain patent protection or FDAregulatory approval and commercialize products more rapidly than we do, which may impact future sales ofto market any of our product candidates, thatwhich would significantly harm our business, results of operations, and prospects.

Even if we obtain regulatory approval for our product candidates, our products will remain subject to extensive regulatory scrutiny.

Even if we receive marketing approval.approval for our product candidates, regulatory authorities may still impose significant restrictions on our product candidates, indicated uses or marketing, or impose ongoing requirements for potentially costly post-approval studies. If the FDA approves the commercial sale of any of our product candidates are approved, they will be subject to ongoing regulatory requirements, including for manufacturing, labeling, packaging, storage, advertising, promotion, sampling, record-keeping, conduct of post-marketing studies, and submission of safety, efficacy, and other post-marketing information, including both federal and state requirements in the United States and requirements of comparable foreign regulatory authorities.

Manufacturers and manufacturers’ facilities are required to comply with extensive requirements imposed by the FDA and comparable foreign regulatory authorities, including, for example, ensuring that quality control and manufacturing procedures conform to current Good Manufacturing Practice (“cGMP”) regulations. As such, we and our contract manufacturers will be subject to continual review and inspections to assess compliance with cGMP and adherence to commitments made in any new drug application (“NDA”) or comparable marketing approval. Accordingly, we and others with whom we work must continue to expend time, money, and effort in all areas of regulatory compliance, including manufacturing, production, and quality control.

The FDA has significant post-marketing authority, including, for example, the authority to require labeling changes based on new safety information and to require post-marketing studies or clinical trials to evaluate serious safety risks related to the use of a drug. The FDA also has the authority to require, as part of an NDA or post-approval, the submission of a REMS. Any REMS required by the FDA may lead to increased costs to assure compliance with new post-approval regulatory requirements and potential requirements or restrictions on the sale of approved products, all of which could lead to lower sales volume and revenue.

Any regulatory approvals that we receive for our product candidates will be competingsubject to limitations on the approved indicated uses for which the product may be marketed and promoted or to the conditions of approval (including the requirement to implement a REMS), or contain requirements for potentially costly post-marketing testing. We will be required to report certain adverse reactions and production problems, if any, to the FDA and comparable foreign regulatory authorities. Any new legislation addressing drug safety issues could result in delays in product development or commercialization, or increased costs to assure compliance. The FDA and other agencies, including the U.S. Department of Justice, closely regulate and monitor the post-approval marketing and promotion of products to ensure that they are manufactured, marketed, and distributed only for the approved indications and in accordance with the provisions of the approved labeling. We will have to comply with requirements concerning advertising and promotion for our products. Promotional communications with respect to prescription drugs are subject to a variety of legal and regulatory restrictions and must be consistent with the information in the product’s approved label. As such, we may not promote our products for indications or uses for which they do not have approval. The holder of an approved NDA or comparable marketing capabilitiesapproval must submit new or supplemental applications and obtain approval for certain changes to the approved product, product labeling, or manufacturing efficiency, areasprocess. We could also be asked to conduct post-marketing studies or clinical trials to verify the safety and efficacy of our products in general or in specific patient subsets.

If a regulatory agency discovers previously unknown problems with a product, such as adverse events of unanticipated severity or frequency, or problems with the facility where the product is manufactured, or disagrees with the promotion, marketing or labeling of a product, such regulatory agency may impose restrictions on that product or us, including requiring withdrawal of the product from the market. If we fail to comply with applicable regulatory requirements, a regulatory agency or enforcement authority may, among other things:

issue warning or untitled letters that would result in adverse publicity;

impose civil or criminal penalties;

suspend or withdraw regulatory approvals;

suspend or impose a clinical hold on any of our ongoing clinical trials;

refuse to approve pending applications or supplements to approved applications submitted by us;

impose restrictions on our operations;

require the conduct of additional post-market clinical trials to assess the safety of the product;

seize or detain products; or

request that we initiate a product recall.

Any government investigation of alleged violations of law could require us to expend significant time and resources in response, and could generate negative publicity. Any failure to comply with ongoing regulatory requirements may significantly and adversely affect our ability to commercialize and generate revenue from our products, if approved. If regulatory sanctions are applied or if regulatory approval is withdrawn, the value of the company and our operating results will be adversely affected.

We are subject to healthcare laws and regulations, which could expose us to criminal sanctions, civil penalties, contractual damages, reputational harm, and diminished profits and future earnings.

Although we do not currently have any products on the market, if we obtain FDA approval for any of our product candidates and begins commercializing our products, we may be subject to additional healthcare statutory and regulatory requirements and enforcement by the federal government and the states and foreign governments in which we have limited or no experience. We expect competition among products will be based on product efficacy and safety, the timing and scope of regulatory approvals, availability of supply, marketing and sales capabilities, product price, reimbursement coverage by government and privateconduct our business. Healthcare providers, physicians, third-party payors, and patent position.others play a primary role in the recommendation and prescription of our product candidates, if approved. Our profitabilityfuture arrangements with third-party payors will expose us to broadly applicable fraud and abuse and other healthcare laws and regulations that may constrain the business or financial position will sufferarrangements and relationships through which we market, sell, and distribute our product candidates, if we cannot compete effectivelyobtain marketing approval. Restrictions under applicable federal and state healthcare laws and regulations include the following:

the federal Anti-Kickback Statute (“AKS”) prohibits, among other things, persons and entities from knowingly and willfully soliciting, offering, receiving, or providing remuneration, directly or indirectly, in cash or in kind, to induce or reward either the referral of an individual for, or the purchase, order, or recommendation of, any good or service, for which payment may be made under federal healthcare programs such as Medicare and Medicaid. The term

“remuneration” has been broadly interpreted to include anything of value. Although there are a number of statutory exceptions and regulatory safe harbors protecting some common activities from prosecution, the exceptions and safe harbors are drawn narrowly. Practices that involve remuneration that may be alleged to be intended to induce prescribing, purchases or recommendations may be subject to scrutiny if they do not qualify for an exception or safe harbor. A person or entity does not need to have actual knowledge of the federal AKS or specific intent to violate it to have committed a violation. The AKS has been interpreted to apply to arrangements between biopharmaceutical manufacturers on the one hand and prescribers, purchasers, and formulary managers, among others, on the other;

the federal False Claims Act imposes criminal and civil penalties, including those from civil whistleblower or qui tam actions, against individuals or entities for knowingly presenting, or causing to be presented, to the federal government, claims for payment that are false or fraudulent or making a false statement to avoid, decrease, or conceal an obligation to pay money to the federal government. Manufacturers can be held liable under the False Claims Act even when they do not submit claims directly to government payors if they are deemed to “cause” the submission of false or fraudulent claims. When an entity is determined to have violated the False Claims Act, the government may impose civil fines and penalties for each false claim, plus treble damages, and exclude the entity from participation in Medicare, Medicaid and other federal healthcare programs;

the federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, imposes criminal and civil liability for, among other things, knowingly and willfully executing, or attempting to execute, a scheme to defraud any healthcare benefit program or making false or fraudulent statements relating to healthcare matters; similar to the federal Anti-Kickback Statute, a person or entity does not need to have actual knowledge of the statute or specific intent to violate it to have committed a violation;

HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act, or HITECH, and their implementing regulations, which also impose obligations, including mandatory contractual terms, with respect to safeguarding the privacy, security, and transmission of individually identifiable health information on health plans, healthcare clearing houses, and certain healthcare providers and their business associates, defined as independent contractors or agents of covered entities that create, receive or obtain protected health information in connection with providing a service for or on behalf of a covered entity. HITECH also created new tiers of civil monetary penalties, amended HIPAA to make civil and criminal penalties directly applicable to business associates, and gave state attorneys general new authority to file civil actions for damages or injunctions in federal courts to enforce the federal HIPAA laws and seek attorneys’ fees and costs associated with pursuing federal civil actions. In addition, there may be additional federal, state and non-U.S. laws which govern the privacy and security of health and other personal information in certain circumstances, many of which differ from each other in significant ways and may not have the same effect, thus complicating compliance efforts;

the federal false statements statute prohibits knowingly and willfully falsifying, concealing or covering up a material fact, or making any materially false statement in connection with the delivery of or payment for healthcare benefits, items, or services;

federal government price reporting laws, which require us to calculate and report complex pricing metrics in an accurate and timely manner to government programs;

federal consumer protection and unfair competition laws, which broadly regulate marketplace activities and activities that potentially harm consumers;

the federal transparency requirements, sometimes referred to as the “Sunshine Act,” under the Patient Protection and Affordable Care Act (the “ACA”) require manufacturers of drugs, devices, biologics, and medical supplies that are reimbursable under Medicare, Medicaid, or the Children’s Health Insurance Program to report annually to the Centers for Medicare and Medicaid Services (“CMS”) information related to payments and other transfers of value to physicians ( as defined by the law), physician assistants, nurse practitioners, clinical nurse specialists, certified registered nurse anesthetists and teaching hospitals, as well as physician ownership and investment interests, and requires applicable manufacturers and group purchasing organizations to report annually the ownership and investment interests held by such physicians and their immediate family members and payments or other “transfers of value” to such physician owners; Such information is subsequently made publicly available in a searchable format on a CMS website, effective January 1, 2022, these reporting obligations will extend to include transfers of value made to certain non-physician assistants and nurse practitioners; and

analogous state laws and regulations, such as state anti-kickback and false claims laws and transparency laws, may apply to sales or marketing arrangements and claims involving healthcare items or services reimbursed by non-governmental third-party payors, including private insurers, and some state laws require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government in addition to requiring drug manufacturers to report information related to payments to physicians and other healthcare providers or marketing expenditures and drug pricing. Several states also impose other marketing restrictions or require pharmaceutical companies to make marketing or price disclosures to the state and require the registration of pharmaceutical sales.

In the event we decide to conduct clinical trials or continue to enroll subjects in our ongoing or future clinical trials, we may be subject to additional privacy restrictions. The collection, use, storage, disclosure, transfer, or other processing of personal data regarding individuals in the marketplace, evenEU, including personal health data, is subject to the EU General Data Protection Regulation (“GDPR”). The GDPR is wide-ranging in scope and imposes numerous requirements on companies that process personal data, including requirements relating to processing health and other sensitive data, obtaining consent of the individuals to whom the personal data relates, providing information to individuals regarding data processing activities, implementing safeguards to protect the security and confidentiality of personal data, providing notification of data breaches, and taking certain measures when engaging third-party processors. The GDPR also imposes strict rules on the transfer of personal data to countries outside the EU, including the United States, and permits data protection authorities to impose large penalties for violations of the GDPR, including potential fines of up to €20 million or 4% of annual global revenues, whichever is greater. The GDPR also confers a private right of action on data subjects and consumer associations to lodge complaints with supervisory authorities, seek judicial remedies, and obtain compensation for damages resulting from violations of the GDPR. In addition, the GDPR includes restrictions on cross-border data transfers. The GDPR may increase our responsibility and liability in relation to personal data that we process where such processing is subject to the GDPR, and we may be required to put in place additional mechanisms to ensure compliance with the GDPR, including as implemented by individual countries. Compliance with the GDPR will be a rigorous and time-intensive process that may increase our cost of doing business or require us to change our business practices, and despite those efforts, there is a risk that we may be subject to fines and penalties, litigation, and reputational harm in connection with our European activities. Further, the United Kingdom’s decision to leave the EU, often referred to as Brexit, has created uncertainty with regard to data protection regulation in the United Kingdom. In particular, it is unclear how data transfers to and from the United Kingdom will be regulated now that the United Kingdom has left the EU.

California recently enacted the California Consumer Privacy Act, or CCPA, which creates new individual privacy rights for California consumers (as defined in the law) and places increased privacy and security obligations on entities handling personal data of consumers or households. The CCPA will require covered companies to provide certain disclosures to consumers about its data collection, use and sharing practices, and to provide affected California residents with ways to opt-out of certain sales or transfers of personal information. The CCPA went into effect on January 1, 2020, and the California State Attorney General submitted final regulations for review on June 2, 2020, which were finalized and are now effective. The California State Attorney General has commenced enforcement actions against violators as of July 1, 2020. Further, a new California privacy law, the California Privacy Rights Act, or CPRA, was passed by California voters on November 3, 2020. The CPRA will create additional obligations with respect to processing and storing personal information that are scheduled to take effect on January 1, 2023 (with certain provisions having retroactive effect to January 1, 2022). Other U.S. states also are considering omnibus privacy legislation and industry organizations regularly adopt and advocate for new standards in these areas. For example, Virginia recently enacted the Consumer Data Protection Act that will become effective will become effective on January 1, 2023, and is similar to the CCPA and CPRA. While the CCPA and CPRA exceptions for certain activities involving data collect in the context of clinical trials, health data governed by California’s Confidentiality of Medical Information Act, and for PHI governed by HIPAA, and other state laws may contain equivalent exemptions, we cannot yet determine the impact the CCPA, CPRA or other such future laws, regulations and standards may have on our business.

Pharmaceutical and other healthcare companies have been prosecuted under these laws for a variety of promotional and marketing activities, such as: providing free trips, free goods, sham consulting fees and grants and other monetary benefits to prescribers; reporting to pricing services inflated average wholesale prices that were then used by federal programs to set reimbursement rates; engaging in off-label promotion; and submitting inflated best price information to the Medicaid Rebate Program to reduce liability for Medicaid rebates. Ensuring that our internal operations and future business arrangements with third parties comply with applicable healthcare laws and regulations will involve substantial costs. It is possible that governmental authorities will conclude that our business practices do not comply with current or future statutes, regulations, or case law involving applicable fraud and abuse or other healthcare laws and regulations. If our operations, including anticipated activities to be conducted by our sales team, were found to be

in violation of any of these laws or any other governmental regulations that may apply to us, we may be subject to significant civil, criminal, and administrative penalties, damages, fines, and exclusion from government funded healthcare programs, such as Medicare and Medicaid, and the curtailment or restructuring of our operations, any of which could substantially disrupt our operations. If any of the physicians or other providers or entities with whom we expect to do business is found not to be in compliance with applicable laws, they may be subject to criminal, civil, or administrative sanctions, including exclusions from government funded healthcare programs.

If any of our product candidates obtain regulatory approval, additional competitors could enter the market with generic or other versions of such drugs, which may result in a material decline in sales of affected products.

Under the Drug Price Competition and Patent Term Restoration Act of 1984 (the “Hatch-Waxman Act”) a pharmaceutical manufacturer may file an abbreviated new drug application (“ANDA”) seeking approval of a generic copy of an approved, small-molecule innovator product. Under the Hatch-Waxman Act, a manufacturer may also submit an NDA under Section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act that references the FDA’s prior approval of the small-molecule innovator product. A 505(b)(2) NDA product may be for a new or improved version of the original innovator product. The Hatch-Waxman Act also provides for certain periods of regulatory exclusivity, which preclude FDA approval (or in some circumstances, FDA filing and reviewing) of an ANDA or 505(b)(2) NDA. For example, a drug that is granted regulatory approval may be eligible for five years of marketing exclusivity in the United States following regulatory approval if that drug is classified as a new chemical entity (“NCE”). A drug can be classified as a NCE if the FDA has not previously approved any other drug containing the same active moiety.

In addition to the benefits of regulatory exclusivity, an innovator NDA holder may have patents claiming the active ingredient, product formulation or an approved use of the drug, which would be listed with the product in the FDA publication, “Approved Drug Products with Therapeutic Equivalence Evaluations,” known as the “Orange Book.” If there are patents listed in the Orange Book, a generic or 505(b)(2) applicant that seeks to market our product before expiration of the patents must include in the ANDA or 505(b)(2) NDA a “Paragraph IV certification,” challenging the validity or enforceability of, or claiming non-infringement of, the listed patent or patents. Appropriate notice of the certification must be given to the innovator, too, and if within 45 days of receiving such notice the innovator sues to protect our patents, approval of the ANDA or 505(b)(2) is stayed for 30 months, or as lengthened or shortened by the court.

Accordingly, if any of our product candidates are approved, competitors could file ANDAs for generic versions of our small-molecule drug products receive regulatory approval.or 505(b)(2) NDAs that reference our small-molecule drug products, respectively. If there are patents listed for our small-molecule drug products in the Orange Book, those ANDAs and 505(b)(2) NDAs would be required to include a certification as to each listed patent indicating whether the ANDA or 505(b)(2) NDA applicant does or does not intend to challenge the patent. We cannot predict which, if any, patents in our current portfolio or patents we may obtain in the future will be eligible for listing in the Orange Book, how any generic competitor would address such patents, whether we would sue on any such patents, or the outcome of any such suit.

Payor approval and reimbursementWe may not be availablesuccessful in securing or maintaining proprietary patent protection for posenacaftor, dirocaftor, nesolicaftor,products and technologies we develop or license. Moreover, if any proprietary combination therapy candidatesof our owned or in-licensed patents that are listed in the Orange Book are successfully challenged by way of a Paragraph IV certification and subsequent litigation, the affected product could immediately face generic competition and our sales would likely decline rapidly and materially. See “Risks Related to Our Intellectual Property Rights.”

The FDA and other regulatory agencies actively enforce the laws and regulations prohibiting the promotion of off-label uses. If we are found to have improperly promoted off-label uses, we may become subject to significant liability.

The FDA and other regulatory agencies strictly regulate the promotional claims that may be made about prescription products. In particular, a product may not be promoted for uses that are not approved by the FDA or such other regulatory agencies as reflected in the product’s approved labeling. For example, if we receive marketing approval for YTX-7739 as a treatment for Parkinson’s disease, physicians may nevertheless prescribe YTX-7739 to their patients in a manner that is inconsistent with the approved label. If we are found to have promoted such off-label uses, we may become subject to significant liability. The federal government has levied large civil and criminal fines against companies for alleged improper promotion and has enjoined several companies from engaging in off-label promotion. The FDA has also requested that companies enter into consent decrees or permanent injunctions under which specified promotional conduct is changed or curtailed. If we cannot successfully manage the promotion of our product candidates, or third-party therapies taken withif approved, we could become subject to significant liability, which would materially adversely affect our drugs, whichbusiness and financial condition.

Even if approved, reimbursement policies could make it difficult or impossible for uslimit our ability to sell our products profitably.product candidates.

Market acceptanceIn the United States and salesmarkets in other countries, patients generally rely on third-party payors to reimburse all or part of posenacaftor, dirocaftor or nesolicaftor, any proprietary combination therapy candidates, or any other product candidates that we develop,the costs associated with their treatment. Sales of our drugs will depend, in part, on the extent to which our drugs will be covered by third-party payors, such as government health programs, commercial insurance, and managed healthcare organizations. Significant uncertainty exists as to the coverage and reimbursement status of any product candidates for which we may obtain regulatory approval.

Market acceptance and sales of our product candidates will depend on reimbursement policies and may be affected by healthcare reform measures. Coverage and adequate reimbursement from governmental healthcare programs, such as Medicare and Medicaid in the United States, and commercial payors are critical to new product acceptance. Third-party payors decide which drugs they will pay for and establish reimbursement levels. In the United States, the principal decisions about reimbursement for thesenew medicines are typically made by CMS. CMS decides whether and to what extent our products and related third party treatments will be available from governmentcovered and reimbursed under Medicare and private payors tend to follow CMS to a substantial degree. Coverage and reimbursement by a third-party payor may depend upon a number of factors, including the third-party payor’s determination that use of a therapeutic is:

a covered benefit under our health administration authorities, private health insurersplan;

safe, effective and other organizations. medically necessary;

appropriate for the specific patient;

cost-effective; and

neither experimental nor investigational.

Government authorities and other third-party payors, such as private health insurers and health maintenance organizations and pharmacy benefit management organizations, decide which medications they will pay for at what tier level and establish reimbursement levels. In the United States, non-governmental payors often rely upon Medicare coverage policy and payment limitations in setting their own coverage and reimbursement policies. Alevels for those medications. Cost containment is a primary trendconcern in the United StatesU.S. healthcare industry and elsewhere is cost containment.elsewhere. Government authorities and these third-party payors have attempted to control costs by limiting coverage and the amount of reimbursement for particular medications. Increasingly, third-party payors are requiring that companies provide them with predetermined discounts from list prices and are challenging the prices charged for medical products. We cannot be sure that reimbursement will be available for anyour product that we commercializecandidates and, if reimbursement is available, what the level of reimbursement will be. Even if we are successful in gaining reimbursement in one country, that does not mean we will achieve reimbursement at the same levels or at all in any other country.such reimbursement. Reimbursement may impact the demand for, or the price of, our product candidates. If reimbursement is not available or is available only at limited levels, we may not be able to successfully commercialize our product candidates. Limited coverage and less than adequate reimbursement may reduce the demand for, or the price of, any product for which we obtain marketingregulatory approval. Obtaining

In some foreign countries, particularly in Canada and European countries, the pricing of prescription pharmaceuticals is subject to strict governmental control. In these countries, pricing negotiations with governmental authorities can take six to 12 months or longer after the receipt of regulatory approval and product launch. To obtain favorable reimbursement for the indications sought or pricing approval in some countries, we may be required to conduct a clinical study that compares the cost-effectiveness of our product candidates with other available therapies. If reimbursement for our productsproduct candidates is unavailable in any country in which we seek reimbursement, if it is limited in scope or amount, if it is conditioned upon our completion of additional clinical trials, or if pricing is set at unsatisfactory levels, our operating results could be materially adversely affected.

Recently enacted and future legislation may be particularly difficult because ofincrease the higher prices often associated with products administered under the supervision of a physician. Reimbursement levels may be impacted by factors including, without limitation, the perceived safety and efficacy of our products relative to the cost (and relative to the perceived safety and efficacydifficulty and cost for available competitive products),us to obtain marketing approval of and commercialize our product candidates and affect the views of independent research organizations on drug pricing and the political climate, many of which factors we cannot control.  Also, reimbursement amounts may reduce the demand for, or the price of, our products. If reimbursement is not available, or is available only to limited levels,prices we may not be able to successfully commercialize posenacaftor, dirocaftor, nesolicaftor, any proprietary combination therapy candidates, or any other product candidates that we develop. We will also be required to establish systemsobtain.

In the United States and programs that assist patients in determining the reimbursement level and in some instances establishing patient economic support programs to alleviate the economic burden of co-pays and/or co-insurance. These patient support programs are complex, costly and require knowledge and expertise that we currently do not possess.

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Thereforeign jurisdictions, there have been a number of legislative and regulatory proposals to changechanges and proposed changes regarding the healthcare system that could prevent or delay regulatory approval of our product candidates, restrict or regulate post-approval activities, and affect our ability to profitably sell any product candidates for which we obtain marketing approval.

Among policy makers and payors in the United States and elsewhere, there is significant interest in some foreign jurisdictionspromoting changes in healthcare systems with the stated goals of containing healthcare costs, improving quality, and/or expanding access. In the United States, the pharmaceutical industry has been a particular focus of these efforts and has been significantly affected by major legislative initiatives. In March 2010, President Obama signed into law the ACA, a sweeping law intended to broaden access to health insurance, reduce or constrain the growth of healthcare spending, enhance remedies against fraud and abuse, add new transparency requirements for the healthcare and health insurance industries, impose new taxes and fees on the health industry, and impose additional health policy reforms.

Among the provisions of the ACA of importance to our product candidates are the following:

an annual, nondeductible fee on any entity that could affectmanufactures or imports certain branded prescription drugs and biologic agents, apportioned among these entities according to their market share in certain government healthcare programs;

a new methodology by which rebates owed by manufacturers under the Medicaid Drug Rebate Program are calculated for drugs that are inhaled, infused, instilled, implanted, or injected;

an increase in the statutory minimum rebates a manufacturer must pay under the Medicaid Drug Rebate Program to 23.1% and 13.0% of the average manufacturer price for branded and generic drugs, respectively;

expansion of healthcare fraud and abuse laws, including the False Claims Act and the AKS, which include, among other things, new government investigative powers and enhanced penalties for non-compliance;

a new Medicare Part D coverage gap discount program, in which manufacturers must agree to offer 50% (increased to 70% in 2019 pursuant to subsequent legislation) point-of-sale discounts off negotiated prices of applicable brand drugs to eligible beneficiaries during their coverage gap period, as a condition for the manufacturer’s outpatient drugs to be covered under Medicare Part D;

extension of manufacturers’ Medicaid rebate liability to covered drugs dispensed to individuals who are enrolled in Medicaid managed care organizations;

expansion of eligibility criteria for Medicaid programs by, among other things, allowing states to offer Medicaid coverage to additional individuals, thereby potentially increasing manufacturers’ Medicaid rebate liability;

expansion of the entities eligible for discounts under the Public Health Service pharmaceutical pricing program;

the requirements under the federal open payments program and its implementing regulations;

a requirement to annually report drug samples that manufacturers and distributors provide to physicians; and

a new Patient-Centered Outcomes Research Institute to oversee, identify priorities in, and conduct comparative clinical effectiveness research, along with funding for such research.

Since its enactment, there have been numerous judicial, administrative, executive, and legislative challenges to certain aspects of the ACA, and we expect there will be additional challenges and amendments to the ACA in the future. Various portions of the ACA are currently undergoing legal and constitutional challenges in the United States Supreme Court and members of Congress have introduced several pieces of legislation aimed at significantly revising or repealing the ACA. The United States Supreme Court is expected to rule on a legal challenge to the constitutionality of the ACA in early 2021. The implementation of the ACA is ongoing, the law appears likely to continue the downward pressure on pharmaceutical pricing, especially under the Medicare program, and may also increase our abilityregulatory burdens and operating costs. Litigation and legislation related to sellthe ACA are likely to continue, with unpredictable and uncertain results.

In addition, other legislative changes have been proposed and adopted since the ACA was enacted. These changes included aggregate reductions to Medicare payments to providers of 2% per fiscal year through 2030. However, pursuant to the Coronavirus Aid, Relief and Economic Security Act, or CARES Act, these Medicare sequester reductions will be suspended from May 1, 2020 through December 31, 2021 due to the COVID-19 pandemic. In January 2013, President Obama signed into law the American Taxpayer Relief Act of 2012, which, among other things, further reduced Medicare payments to several providers, and increased the statute of limitations period for the government to recover overpayments to providers from three to five years. We expect that the ACA, as well as other healthcare reform measures that may be adopted in the future, may result in additional reductions in Medicare and other healthcare funding, more rigorous coverage criteria, new payment methodologies and in additional downward pressure on the price that we receive for any future products profitably. For example, theapproved product. Any reduction in reimbursement from Medicare or other government programs may result in a similar reduction in payments from private payers. The implementation of cost containment measures or other healthcare reforms may prevent us from being able to generate revenue, attain profitability, or commercialize our products.

The former Trump administration’s budget proposal for fiscal year 2021 includesincluded a $135 billion allowance to support legislative proposals seeking to reduce drug prices, increase competition, lower out-of-pocket drug costs for patients, and increase patient access to lower-cost generic and biosimilar drugs. On March 10, 2020, the former Trump administration sent “principles” for drug pricing to Congress, calling for legislation that would, among other things, cap Medicare Part D beneficiary out-of-pocket pharmacy expenses, provide an option to cap Medicare Part D beneficiary monthly out-of-pocket expenses, and place limits on pharmaceutical price increases. Further, the former Trump administration also previously released a “Blueprint” to lower drug prices and reduce out of pocket costs of drugs that containedcontains additional proposals to increase drug manufacturer competition, increase the negotiating power of certain federal healthcare programs, incentivize manufacturers to lower the list price of their products and reduce the out of pocket costs of drug products paid by consumers. The U.S. Department of Health and Human Services, or HHS, has solicitedalready started the process of soliciting feedback on some of these measures and, has implementedat the same time, is immediately implementing others under its existing authority. TheseFor example, in May 2019, CMS issued a final rule to allow Medicare Advantage Plans the option of using step therapy for Part B drugs beginning January 1, 2020. However, it is unclear whether the Biden administration will challenge, reverse, revoke or otherwise modify these executive and administrative actions after January 20, 2021.

We cannot be sure whether additional legislative changes will be enacted, or whether the FDA regulations, guidance or interpretations will be changed, or what the impact of such changes on the marketing approvals of our product candidates, if any, may be. In addition, increased scrutiny by the U.S. Congress of the FDA’s approval process may significantly delay or prevent marketing approval, as well as subject we to more stringent labeling and post-marketing testing and other requirements.

At the state level, legislatures have increasingly passed legislation and implemented regulations designed to control pharmaceutical product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing.

It is likely that federal and state legislatures within the United States and foreign governments will continue to consider changes to existing healthcare legislation. We cannot predict the reform initiatives that may be adopted in the future or whether initiatives that have been adopted will be repealed or modified. The continuing efforts of the government, insurance companies, managed care organizations, and other healthcare payors of to contain or reduce costs of healthcare may adversely affect the demand for any product candidates for which we may obtain regulatory changesapproval, our ability to set a price that we believe is fair for our products, our ability to obtain coverage and reimbursement approval for a product, our ability to generate revenue and achieve or maintain profitability; and the level of taxes that we are required to pay.

Our future growth may negatively impact thedepend, in part, on our ability to commercialize our product candidates in foreign markets, where we would be subject to additional regulatory burdens and other risks and uncertainties.

Our future profitability may depend, in part, on our ability to commercialize our product candidates in foreign markets for which we may rely on collaboration with third parties. If we commercialize our product candidates in foreign markets, we would be subject to additional risks and uncertainties, including:

our customers’ ability to obtain reimbursement for any future products, following approval. The availabilityour product candidates in foreign markets;

our inability to directly control commercial activities because we are relying on third parties;

the burden of generic treatments maycomplying with complex and changing foreign regulatory, tax, accounting, and legal requirements;

different medical practices and customs in foreign countries affecting acceptance in the marketplace;

import or export licensing requirements;

longer accounts receivable collection times;

longer lead times for shipping;

language barriers for technical training;

reduced protection of intellectual property rights in some foreign countries;

the existence of additional potentially relevant third-party intellectual property rights;

foreign currency exchange rate fluctuations; and

the interpretation of contractual provisions governed by foreign laws in the event of a contract dispute.

Foreign sales of our product candidates could also substantially reducebe adversely affected by the likelihoodimposition of reimbursement for any future products, including posenacaftor, dirocaftorgovernmental controls, political and nesolicaftor or any proprietary combination therapy candidates. The application of user fees to generic drug products will likely expedite theeconomic instability, trade restrictions, and changes in tariffs.

Obtaining and maintaining regulatory approval of additional generic drug treatments. We expectour product candidates in one jurisdiction does not mean that we will be successful in obtaining regulatory approval of our product candidates in other jurisdictions.

In order to experience pricing pressures in connectionmarket any product outside of the United States, however, we must establish and comply with the salenumerous and varying safety, efficacy, and other regulatory requirements of posenacaftor, dirocaftor, nesolicaftor, any proprietary combination therapyother countries. Obtaining and maintaining regulatory approval of our product candidates andin one jurisdiction does not guarantee that we will be able to obtain or maintain regulatory approval in any other product candidate that we develop, due to the trend toward managed healthcare, the increasing influence of health maintenance organizations and additional legislative changes.

In addition, there may be significant delaysjurisdiction, but a failure or delay in obtaining reimbursement for approved products, and coverageregulatory approval in one jurisdiction may be more limited thanhave a negative effect on the purposes for which the product is approved byregulatory approval process in others. For example, even if the FDA or other comparable foreign regulatory authority grants marketing approval of a product candidate, comparable regulatory authorities in foreign jurisdictions must also approve the manufacturing, marketing, and promotion of the product candidate in those countries. Approval procedures vary among jurisdictions and can involve requirements and administrative review periods different from those in the United States, including additional preclinical studies or clinical trials as clinical trials conducted in one jurisdiction may not be accepted by regulatory authorities in other countries. Moreover, eligibility for reimbursement does not imply that any product will be paid forjurisdictions. The marketing approval processes in all cases or at a rate that covers our costs, including research, development, manufacture, sale and distribution. Interim payments for new products, if applicable,other countries may also not be sufficient to cover our costs and may not be made permanent. Payment rates may vary according to the useimplicate all of the product and the clinical setting in which it is used, may be based on payments allowed for lower cost products that are already reimbursed, and may be incorporated into existing payments for other services. Net prices for products may be reduced by mandatory discounts or rebates required by government healthcare programs or private payors and by any future relaxation of laws that presently restrict imports of products from countries where they may be sold at lower prices thanrisks detailed above regarding FDA approval in the United States. Third-party payors often rely upon Medicare coverage policyStates, as well as other risks. In many jurisdictions outside the United States, a product candidate must be approved for reimbursement before it can be approved for sale in that jurisdiction. In some cases, the price that we intend to charge for our products is also subject to approval.

Obtaining foreign regulatory approvals and payment limitationscompliance with foreign regulatory requirements could result in setting their own reimbursement policies, however reimbursementsignificant delays, difficulties, and levelscosts for we and could delay or prevent the introduction of reimbursement may also vary within a country based on the individual decisions of private payors.

Our inabilityour products in certain countries. Failure to promptly obtain coverage and profitable payment rates from both government-funded and private payors formarketing approval in other countries or any ofdelay or other setback in obtaining such approval would impair our ability to market our product candidates including posenacaftor, dirocaftor and nesolicaftor and any proprietary combination therapy candidates,in such foreign markets. Any such impairment would reduce the size of our potential market, which could have a material adverse effectimpact on our operating results, our ability to raise capital needed to commercialize products and our overall financial condition.

We may expend our limited resources to pursue a particular product candidate or indication and fail to capitalize on product candidates or indications that may be more profitable or for which there is a greater likelihood of success.

The success of our business depends primarily on our ability to identify, develop and commercialize product candidates. Because we have limited financial and managerial resources, we focus on research programs and product candidates for the indications that take advantage of our deep expertise and knowledge and that we believe are the most scientifically and commercially promising. Our resource allocation decisions may cause us to fail to capitalize on viable scientific or commercial products or profitable market opportunities. In addition, we may spend valuable time and managerial and financial resources on research programs and product candidates for specific indications that ultimately do not yield any scientifically or commercially viable products. If we do not accurately evaluate the scientific and commercial potential or target market for a particular product candidate, we may relinquish valuable rights to that product candidate through collaboration, licensing or other royalty arrangements in situations where it would have been more advantageous for us to retain sole rights to development and commercialization.

Risks Related to Government Regulation

We may be subject, directly or indirectly, to federal and state healthcare fraud and abuse laws and health information privacy and security laws. Some of these laws were recently amended, and their interpretation following such amendments remains unclear. If we are unable to comply, or have not fully complied, with such laws, we could face substantial penalties.

Our current and future operations may be directly, or indirectly through our customers, subject to various federal and state fraud and abuse laws, including, without limitation, the federal anti-kickback statute. These laws may impact, among other things, our research, proposed sales, marketing and education programs. In addition, we may be subject to patient privacy regulation by both the federal government and the states in which we conduct our business. The laws that may affect our ability to operate include:

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the federal anti-kickback statute which prohibits, among other things, persons or entities from knowingly and willfully soliciting, offering, receiving or paying any remuneration (including any kickback, bribe, or rebate), directly or indirectly, overtly or covertly, in cash or in kind, to induce or reward either the referral of an individual for, or the purchase, lease, order or recommendation of, any good, facility, item or service, for which payment may be made, in whole or in part, under federal healthcare programs such as Medicare and Medicaid;

the federal false claims laws, including civil whistleblower or qui tam actions, and civil monetary penalties, which prohibit, among other things, individuals or entities from knowingly presenting, or causing to be presented, to the federal government, claims for payment or approval that are false or fraudulent or from knowingly making a false statement to improperly avoid, decrease or conceal an obligation to pay money to the federal government;

the federal Health Insurance Portability and Accountability Act of 1996 (HIPAA) which, among other things, imposes criminal liability for knowingly and willfully executing, or attempting to execute, a scheme to defraud any healthcare benefit program or to obtain, by means of false or fraudulent pretenses, representations, or promises, any of the money or property owned by, or under the custody or control of, any healthcare benefit program, regardless of the payor (e.g., public or private) and knowingly or willfully falsifying, concealing, or covering up by any trick or device a material fact or making any materially false statement using or making any false or fraudulent document, in connection with the delivery of, or payment for, healthcare benefits, items or services relating to healthcare matters;

HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act, or HITECH, and its implementing regulations, and as amended by the final HIPAA omnibus rule, Modifications to the HIPAA Privacy, Security, Enforcement, and Breach Notification Rules Under HITECH and the Genetic Information Nondiscrimination Act; Other Modifications to HIPAA, published in January 2013, which imposes certain obligations, including mandatory contractual terms, with respect to safeguarding the privacy, security and transmission of individually identifiable health information on entities subject to the rule, such as health plans, clearinghouses and certain healthcare providers and their business associates that create, use or disclose individually identifiable health information on their behalf;

the Federal Food, Drug, and Cosmetic Act, or FDCA, which prohibits, among other things, the distribution of adulterated or misbranded drugs or medical devices;

the federal Physician Payments Sunshine Act, enacted as part of the Patient Protection and Affordable Care Act and the Health Care and Education Reconciliation Act of 2010, collectively referred to herein as the Affordable Care Act, or the ACA, and its implementing regulations, which requires certain manufacturers of drugs, devices, biologicals and medical supplies to report to CMS information related to payments and other transfers of value made to physicians, as defined by such law, and teaching hospitals, as well as ownership and investment interests held by physicians and their immediate family members; and

analogous state laws and regulations, including: state anti-kickback and false claims laws, which may apply to our business practices, including but not limited to, research, distribution, sales and marketing arrangements and claims involving healthcare items or services reimbursed by state governmental and non-governmental third-party payors, including private insurers; state laws that require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government; state laws and regulations that require manufacturers to file reports relating to pricing and marketing information, which requires tracking gifts and other remuneration and items of value provided to healthcare professionals and entities; and state and local laws that require the registration of pharmaceutical sales representatives.

Further, the ACA, among other things, amends the intent requirement of the federal anti-kickback and criminal health care fraud statutes. A person or entity can now be found guilty of fraud or false claims under ACA without actual knowledge of the statute or specific intent to violate it. In addition, ACA provides that the government may assert that a claim including items or services resulting from a violation of the federal anti-kickback statute constitutes a false or fraudulent claim for purposes of the false claims statutes.

Possible sanctions for violation of these laws include significant monetary fines, civil and criminal penalties, exclusion from Medicare, Medicaid and other government programs, forfeiture of amounts collected in violation of such prohibitions, imprisonment, and integrity oversight and ongoing monitoring. Any violations of these laws, or any action against us for violation of these laws, even if we successfully defend against it, could result in a material adverse effect on our reputation, business, results of operations, and financial condition.prospects.

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In addition, regulators globally are also imposing greater monetary fines for privacy violations. For example, in 2016, the E.U. adopted a new regulation governing data practices and privacy called the General Data Protection Regulation, or GDPR, which became effective on May 25, 2018. The GDPR applies to any company established in the E.U. as well as to those outside the E.U. if they collect and use personal data in connection with the offering goods or services to individuals in the E.U. or the monitoring of their behavior.  The GDPR enhances data protection obligations for processors and controllers of personal data, including, for example, expanded disclosures about how personal information is to be used, limitations on retention of information, mandatory data breach notification requirements and onerous new obligations on services providers. Non-compliance with the GDPR may result in monetary penalties of up to €20 million or 4% of worldwide revenue, whichever is higher. The GDPR and other changes in laws or regulations associated with the enhanced protection of certain types of personal data, such as healthcare data or other sensitive information, could greatly increase our cost of providing our products and services or even prevent us from offering certain services in jurisdictions that we operate in.

In addition, there has been a trend of increased state regulation of payments made to physicians for marketing. Some states, such as California, Massachusetts and Vermont, mandate implementation of corporate compliance programs, along with the tracking and reporting of gifts, compensation, and other remuneration to physicians.

The scope and enforcement of these laws is uncertain and subject to change in the current environment of health care reform, especially in light of the lack of applicable precedent and regulations. Such changes are impossible to predict. It is possible that some of our business activities could be subject to challenge by federal or state regulatory authorities under one or more of these laws. Any such challenge could have a material adverse effect on our reputation, business, results of operations, and financial condition. Any state or federal regulatory review of us, regardless of the outcome, would be costly and time-consuming, and could have a material adverse effect on our business, financial condition and results of operations.

Our employees, independent contractors, consultants, commercial partners, and vendors may engage in misconduct or other improper activities, including noncompliance with regulatory standards and requirements and insider trading, which could have a material adverse effect on our business.requirements.

We are exposed to the risk of employee fraud, misconduct, or other misconduct.illegal activity by our employees, independent contractors, consultants, commercial partners, and vendors. Misconduct by employeesthese parties could include intentional, failures toreckless, and negligent conduct that fails to: comply with the laws of the FDA regulations,and other comparable foreign regulatory authorities; provide true, complete and accurate information to the FDA and other comparable foreign regulatory authorities; comply with manufacturing standards we have established,established; comply with federal and state healthcare fraud and abuse laws in the United States and regulations,similar foreign fraudulent misconduct laws; or report financial information or data accurately or to disclose unauthorized activities to us. If we obtain FDA approval of any of our product candidates and begins commercializing those products in the United States, our potential exposure under such laws will

increase significantly, and our costs associated with compliance with such laws are also likely to increase. In particular, sales, marketing, and other business arrangements in the healthcare industry are subject to extensive laws and regulations intendeddesigned to prevent fraud, kickbacks, self-dealing, and other abusive practices. These laws and regulations may restrict or prohibit a wide range of pricing, discounting, marketing and promotion, sales and commission, certain customer incentive programs, and other business arrangements. Employee misconduct couldarrangements generally. Activities subject to these laws also involve the improper use of information obtained in the course of patient recruitment for clinical trials, which could result in regulatory sanctions and cause serious harm to our reputation. We have adopted a Codecode of Business Conductbusiness conduct and Ethicsethics, but it is not always possible to identify and deter employee misconduct by employees and third parties, and the precautions we take to detect and prevent misconductthis activity may not be effective in controlling unknown or unmanaged risks or losses or in protecting us from governmental investigations or other actions or lawsuits stemming from a failure to be in compliance with such laws or regulations.laws. If any such actions are instituted against us, and we are not successful in defending ourselvesitself or asserting our rights, those actions could have a significant impact on our business, and results of operations, including the imposition of significant fines or other sanctions.

Health care reform measuresIf we or any contract manufacturers and suppliers we engage fail to comply with environmental, health, and safety laws and regulations, we could adversely affectbecome subject to fines or penalties or incur costs that could have a material adverse effect on the success of our business.

InWe and any contract manufacturers and suppliers we engage are subject to numerous federal, state, and local environmental, health, and safety laws, regulations, and permitting requirements, including those governing laboratory procedures; the United Statesgeneration, handling, use, storage, treatment, and foreign jurisdictions, there have been a numberdisposal of legislativehazardous and regulatory changesregulated materials and wastes; the emission and discharge of hazardous materials into the ground, air, and water; and employee health and safety. Under certain environmental laws, we could be held responsible for costs relating to any contamination at our current or past facilities and at third-party facilities. We also could incur significant costs associated with civil or criminal fines and penalties.

We could be adversely affected by violations of the U.S. Foreign Corrupt Practices Act (“FCPA”) and other worldwide anti-bribery laws.

Our business activities may be subject to the healthcare systemFCPA and similar anti-bribery or anti-corruption laws, regulations or rules of other countries in which we operate, including the U.K. Bribery Act. The FCPA generally prohibits offering, promising, giving, or authorizing others to give anything of value, either directly or indirectly, to a non-U.S. government official in order to influence official action, or otherwise obtain or retain business. The FCPA also requires public companies to make and keep books and records that could affect our future results of operations. In particular, there have beenaccurately and continue to be a number of initiatives atfairly reflect the U.S. federal and state levels that seek to reduce healthcare costs. The ACA, which includes measures to significantly change the way health care is financed by both governmental and private insurers, was enacted in March 2010. Among the provisionstransactions of the ACAcorporation and to devise and maintain an adequate system of greatest importanceinternal accounting controls. Our business is heavily regulated and therefore involves significant interaction with public officials, including officials of non-U.S. governments. Additionally, in many other countries, the healthcare providers who prescribe pharmaceuticals are employed by their government, and the purchasers of pharmaceuticals are government entities; therefore, our dealings with these prescribers and purchasers are subject to regulation under the FCPA. Recently the SEC and Department of Justice have increased their FCPA enforcement activities with respect to biotechnology and pharmaceutical companies. There is no certainty that all of our employees, agents, contractors, or collaborators, or those of our affiliates, will comply with all applicable laws and biotechnology industry areregulations, particularly given the following:

an annual, nondeductible fee on any entity that manufactureshigh level of complexity of these laws. Violations of these laws and regulations could result in fines, criminal sanctions against us, our officers, or imports certain branded prescription drugs and biologic products, apportioned among these entities according to their market share in certain government healthcare programs;

newour employees, the closing down of our facilities, requirements to report certain financial arrangements with physicians, as defined by thereunder,obtain export licenses, cessation of business activities in sanctioned countries, implementation of compliance programs, and teaching hospitals, including reporting any “transferprohibitions on the conduct of value” made or distributed to physicians and teaching hospitals and reporting any ownership interests held by physicians and their immediate family members;

a new Patient-Centered Outcomes Research Institute to oversee, identify priorities in, and conduct comparative clinical effectiveness research, along with funding for such research; and

establishment of a Center for Medicare Innovation at the Centers for Medicare & Medicaid Services to test innovative payment and service delivery models to lower Medicare and Medicaid spending, potentially including prescription drug spending.

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At this time, the full effect that the ACA would have on our business remains unclear. There remain judicial, Congressional and efforts by the current administration to challenge certain aspects of the ACA. Legislation has been drafted and enacted to repeal and replace parts of the ACA, but no comprehensive ACA replacement law has been enacted. However, on December 14, 2018, a U.S. District Court judge in the Northern District of Texas ruled that the individual mandate portion of the ACA is an essential and inseverable feature of the ACA, and therefore because the mandate was repealed as part of the Tax Cuts and Jobs Act, the remaining provisions of the ACA are invalid as well. Additionally, on December 18, 2019, the U.S. Court of Appeals for the 5th Circuit upheld the District Court ruling that the individual mandate was unconstitutional and remanded the case back to the District Court to determine whether the remaining provisions of the ACA are invalid as well. On March 2, 2020, the United States Supreme Court granted the petitions for writs of certiorari to review this case, and has allotted one hour for oral arguments, which are expected to occur in the fall. It is unclear how such litigation and other efforts to repeal and replace the ACA will impact the ACA and our business. We cannot predict any initiatives that may be adopted in the future.

Individual states have become increasingly aggressive in passing legislation and implementing regulations designed to control pharmaceutical and biological product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access, and marketing cost disclosure and transparency measures, and designed to encourage importation from other countries and bulk purchasing. Legally mandated price controls on payment amounts by third-party payors or other restrictionsAny such violations could harm our business, results of operations, financial condition and prospects. In addition, regional healthcare authorities and individual hospitals are increasingly using bidding procedures to determine what pharmaceutical products and which suppliers will be included in their prescription drug and other healthcare programs. This could reduce ultimate demand for our products or put pressure on our product pricing, which could negatively affect our business, results of operations, financial condition and prospects.

In addition, given recent federal and state government initiatives directed at lowering the total cost of healthcare, Congress and state legislatures will likely continue to focus on healthcare reform, the cost of prescription drugs and biologics and the reform of the Medicare and Medicaid programs. While we cannot predict the full outcome of any such legislation, it may result in decreased reimbursement for drugs and biologics, which may further exacerbate industry-wide pressure to reduce prescription drug prices. This could harm our ability to generate revenues. Increases in importation or re-importation of pharmaceutical products from foreign countries into the United States could put competitive pressureinclude prohibitions on our ability to profitably price our products, which, in turn, could adversely affect our business, results of operations, financial condition and prospects. We might elect not to seek approval for or marketoffer our products in foreign jurisdictions in order to minimize the risk of re-importation, which could also reduce the revenue we generate from our product sales. It is also possible that other legislative proposals having similar effects will be adopted.

Furthermore, regulatory authorities’ assessment of the dataone or more countries and results required to demonstrate safety and efficacy can change over time and can be affected by many factors, such as the emergence of new information, including on other products, changing policies and agency funding, staffing and leadership. We cannot be sure whether future changes to the regulatory environment will be favorable or unfavorable to our business prospects. For example, average review times at the FDA for marketing approval applications can be affected by a variety of factors, including budget and funding levels and statutory, regulatory and policy changes.

Additionally, it is possible that additional governmental action is taken to address the COVID-19 pandemic. For example, on April 18, 2020, CMS announced that Qualified Health Plan issuers under the ACA may suspend activities related to the collection and reporting of quality data that would have otherwise been reported between May and June 2020 given the challenges healthcare providers are facing responding to the COVID-19 virus.

The withdrawal of the United Kingdom, or U.K., from the European Union, or E.U., commonly referred to as “Brexit,” may adversely impact our ability to obtain regulatory approvals of our product candidates in the E.U., result in restrictions or imposition of taxes and duties for importing our product candidates into the E.U., and may require us to incur additional expenses in order to develop, manufacture and commercialize our product candidates in the E.U.

Following the result of a referendum in 2016, the U.K. left the E.U. on January 31, 2020, commonly referred to as Brexit.  Pursuant to the formal withdrawal arrangements agreed between the U.K. and the E.U., the U.K. will be subject to a transition period until December 31, 2020, or the Transition Period, during which E.U. rules will continue to apply.  Negotiations between the U.K. and the E.U. are expected to continue in relation to the customs and trading relationship between the U.K. and the E.U. following the expiry of the Transition Period.  

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Since a significant proportion of the regulatory framework in the U.K. applicable to our business and our product candidates is derived from E.U. directives and regulations, Brexit, following the Transition Period, could materially impact the regulatory regime with respect to the development, manufacture, importation, approval and commercialization ofdamage our product candidates in the U.K. or the E.U. For example, as a result of the uncertainty surrounding Brexit, the European Medicines Agency (the “EMA”) relocated to Amsterdam from London. Following the Transition Period, the U.K. will no longer be covered by the centralized procedures for obtaining E.U-wide marketing authorization from the EMA and, unless a specific agreement is entered into, a separate process for authorization of drug products, includingreputation, our product candidates, will be required in the U.K., the potential process for which is currently unclear. Any delay in obtaining, or an inability to obtain, any marketing approvals, as a result of Brexit or otherwise, would prevent us from commercializingbrand, our product candidates in the U.K. or the E.U. and restrict our ability to generate revenue and achieve and sustain profitability. In addition, we may be required to pay taxes or duties or be subjected to other hurdles in connection with the importation of our product candidates into the E.U., or we may incur expenses in establishing a manufacturing facility in the E.U. in order to circumvent such hurdles. If any of these outcomes occur, we may be forced to restrict or delayinternational expansion efforts, to seek regulatory approval in the U.K. or the E.U. for our product candidates, or incur significant additional expenses to operate our business, which could significantly and materially harm or delay our ability to generate revenues or achieve profitability of our business. Any further changes in international trade, tariff and import/export regulations as a result of Brexit or otherwise may impose unexpected duty costs or other non-tariff barriers on us. These developments, or the perception that any of them could occur, may significantly reduce global trade and, in particular, trade between the impacted nations and the U.K. It is also possible that Brexit may negatively affect our ability to attract and retain employees, particularly those from the E.U.and our business, prospects, operating results, and financial condition.

Risks Related to ProtectingOur Reliance on Third Parties

We depend on our collaboration with Merck and may in the future depend on other collaborations with third parties for the research, development and commercialization of certain of the product candidates we may develop. If any such collaborations are not successful, we may not be able to realize the market potential of those product candidates.

We have entered into a collaboration agreement with Merck and may seek other third-party collaborators for the research, development, and commercialization of certain of the product candidates we may develop. Our likely collaborators for any other collaboration arrangements include large and mid-size pharmaceutical companies, regional and national pharmaceutical companies, biotechnology companies and academic institutions. Under our collaboration with Merck, we have, and if we enter into any such arrangements with any other third parties, we will likely have, shared or limited control over the amount and timing of resources that our collaborators dedicate to the development or potential commercialization of any product candidates we may seek to develop with them. Our ability to generate revenue from these arrangements with commercial entities will depend on our collaborators’ abilities to successfully perform the functions assigned to them in these arrangements. We cannot predict the success of any collaboration that we enter into.

Collaborations involving our research programs, or any product candidates we may develop, pose the following risks to we:

collaborators generally have significant discretion in determining the efforts and resources that they will apply to these collaborations;

collaborators may not properly obtain, maintain, enforce, or defend intellectual property or proprietary rights relating to our product candidates or research programs or may use our proprietary information in such a way as to expose us to potential litigation or other intellectual property related proceedings, including proceedings challenging the scope, ownership, validity and enforceability of our intellectual property;

collaborators may own or co-own intellectual property covering our product candidates or research programs that results from our collaboration with them, and in such cases, we may not have the exclusive right to commercialize such intellectual property or such product candidates or research programs;

we may need the cooperation of our collaborators to enforce or defend any intellectual property we contribute to or that arises out of our collaborations, which may not be provided to us;

disputes may arise between the collaborators and us that result in the delay or termination of the research, development, or commercialization of our product candidates or research programs or that result in costly litigation or arbitration that diverts management attention and resources;

collaborators may decide to not pursue development and commercialization of any product candidates we develop or may elect not to continue or renew development or commercialization programs based on clinical trial results, changes in the collaborator’s strategic focus or available funding or external factors such as an acquisition that diverts resources or creates competing priorities;

collaborators may delay clinical trials, provide insufficient funding for a clinical trial program, stop a clinical trial or abandon a product candidate, repeat or conduct new clinical trials, or require a new formulation of a product candidate for clinical testing;

collaborators could independently develop, or develop with third parties, products that compete directly or indirectly with our product candidates or research programs if the collaborators believe that competitive products are more likely to be successfully developed or can be commercialized under terms that are more economically attractive than ours;

collaborators with marketing and distribution rights to one or more product candidates may not commit sufficient resources to the marketing and distribution of such product candidates;

we may lose certain valuable rights under circumstances identified in our collaborations, including if we undergo a change of control;

collaborators may undergo a change of control and the new owners may decide to take the collaboration in a direction which is not in our best interest;

collaborators may become bankrupt, which may significantly delay our research or development programs, or may cause us to lose access to valuable technology, know-how or intellectual property of the collaborator relating to our products, product candidates or research programs;

key personnel at our collaborators may leave, which could negatively impact our ability to productively work with our collaborators;

collaborations may require us to incur short and long-term expenditures, issue securities that dilute our stockholders, or disrupt our management and business;

collaborations may be terminated and, if terminated, may result in a need for additional capital to pursue further development or commercialization of the applicable product candidates or our discovery engine platform; and

collaboration agreements may not lead to development or commercialization of product candidates in the most efficient manner or at all. If a present or future collaborator of ours were to be involved in a business combination, the continued pursuit and emphasis on our development or commercialization program under such collaboration could be delayed, diminished, or terminated.

We may face significant competition in seeking appropriate collaborations. Recent business combinations among biotechnology and pharmaceutical companies have resulted in a reduced number of potential collaborators. In addition, the negotiation process is time-consuming and complex, and we may not be able to negotiate collaborations on a timely basis, on acceptable terms, or at all. If we are unable to do so, we may have to curtail the development of the product candidate for which we are seeking to collaborate, reduce or delay our development program or one or more of our other development programs, delay our potential commercialization or reduce the scope of any sales or marketing activities, or increase our expenditures and undertake development or commercialization activities at our own expense. If we elect to increase our expenditures to fund development or commercialization activities on our own, we may need to obtain additional capital, which may not be available to it on acceptable terms or at all. If we do not have sufficient funds, we may not be able to further develop product candidates or bring them to market and generate product revenue.

Under our collaboration with Merck, and if we enter into other collaborations to develop and potentially commercialize any product candidates, we may not be able to realize the benefit of such transactions if us or our collaborator elects not to exercise the rights granted under the agreement or if us or our collaborator are unable to successfully integrate a product candidate into existing operations and company culture. In addition, if our agreement with any of our collaborators terminates, our access to technology and intellectual property licensed to us by that collaborator may be restricted or terminate entirely, which may delay our continued development of our product candidates utilizing the collaborator’s technology or intellectual property or require us to stop development of those product candidates completely. We may also find it more difficult to find a suitable replacement collaborator or attract new collaborators, and our development programs may be delayed or the perception of our in the business and financial communities could be adversely affected. Many of the risks relating to product development, regulatory approval, and commercialization described in this “Risk Factors” section also applies to the activities of our collaborators and any negative impact on our collaborators may adversely affect us.

Our drug development programs and the potential commercialization of our product candidates will require substantial additional cash to fund expenses. For some of our product candidates, we may decide to collaborate with pharmaceutical and biotechnology companies for the development and potential commercialization of those product candidates, such as those that may result from our collaboration with Merck.

Whether we reach a definitive agreement for a collaboration will depend, among other things, upon our assessment of the collaborator’s resources and expertise, the terms and conditions of the proposed collaboration and the proposed collaborator’s evaluation of a number of factors. Those factors may include the design or results of clinical studies, the likelihood of approval by the FDA or similar regulatory authorities outside the United States, the potential market for the subject product candidate, the costs and complexities of manufacturing and delivering such product candidate to patients, the potential of competing products, the existence of uncertainty with respect to our ownership of technology, which can exist if there is a challenge to such ownership without regard to the merits of the challenge, and industry and market conditions generally. The collaborator may also consider alternative product candidates or technologies for similar indications that may be available to collaborate on and whether such a collaboration could be more attractive than the one with us for our product candidate. The terms of any collaborations or other arrangements that we may establish may not be favorable to it.

In addition, our collaboration with Merck and any future collaborations that we enter into may not be successful. The success of our collaboration arrangements will depend heavily on the efforts and activities of our collaborators. Collaborators generally have significant discretion in determining the efforts and resources that they will apply to these collaborations. Disagreements between parties to a collaboration arrangement regarding clinical development and commercialization matters can lead to delays in the development process or commercializing the applicable product candidate and, in some cases, termination of the collaboration arrangement. These disagreements can be difficult to resolve if neither of the parties has final decision-making authority. Collaborations with pharmaceutical or biotechnology companies and other third parties often are terminated or allowed to expire by the other party. Termination of our collaboration with Merck or any such termination or expiration of future collaborations would adversely affect us financially and could harm our business reputation.

We rely, and expect to continue to rely, on third parties to conduct any preclinical studies and clinical trials for our product candidates. If these third parties do not successfully carry out their contractual duties or meet expected deadlines, we may not be able to obtain regulatory approval for or commercialize our product candidates and our business could be substantially harmed.

We do not have the ability to independently conduct preclinical studies and clinical trials. We rely on medical institutions, clinical investigators, contract laboratories, and other third parties, such as CROs, to conduct preclinical studies and clinical trials on our product candidates. We enter into agreements with third-party CROs to provide monitors for and to manage data for our clinical trials. We will rely heavily on these parties for execution of clinical trials for our product candidates and control only certain aspects of their activities. As a result, we will have less direct control over the conduct, timing, and completion of these clinical trials and the management of data developed through clinical trials than would be the case if we were relying entirely upon our own staff. Communicating with outside parties can also be challenging, potentially leading to mistakes as well as difficulties in coordinating activities. Outside parties may:

have staffing difficulties;

fail to comply with contractual obligations;

experience regulatory compliance issues;

undergo changes in priorities or become financially distressed; or

form relationships with other entities, some of which may be our competitors.

These factors may materially adversely affect the willingness or ability of third parties to conduct our clinical trials and may subject us to unexpected cost increases that are beyond our control. Nevertheless, we are responsible for ensuring that each of our clinical trials is conducted in accordance with the applicable protocol, legal, regulatory, and scientific requirements and standards, and our reliance on CROs does not relieve us of our regulatory responsibilities. We and our CROs are required to comply with regulations and

guidelines, including Good Clinical Practices (“GCPs”) for conducting, monitoring, recording, and reporting the results of clinical trials to ensure that the data and results are scientifically credible and accurate, and that the study patients are adequately informed of the potential risks of participating in clinical trials. These regulations are enforced by the FDA, the Competent Authorities of the Member States of the European Economic Area and comparable foreign regulatory authorities for any products in clinical development. The FDA enforces GCP regulations through periodic inspections of clinical study sponsors, principal investigators and study sites. If we or our CROs fail to comply with applicable GCPs, the clinical data generated in our clinical trials may be deemed unreliable and the FDA or comparable foreign regulatory authorities may require us to perform additional clinical trials before approving our marketing applications. We cannot assure you that, upon inspection, the FDA will determine that any of our clinical trials comply with GCPs. In addition, our clinical trials must be conducted with product candidates produced under cGMP regulations and will require a large number of test patients. Our failure or the failure of our CROs to comply with these regulations may require us to repeat clinical trials, which would delay the regulatory approval process and could also subject it to enforcement action up to and including civil and criminal penalties.

Although we design our clinical trials for our product candidates, CROs conduct all of the clinical trials. As a result, many important aspects of the clinical trials are outside of our direct control. In addition, the CROs may not perform all of their obligations under arrangements with us or in compliance with regulatory requirements, but we remain responsible and are subject to enforcement action that may include civil penalties and criminal prosecution for any violations of FDA laws and regulations during the conduct of our clinical trials. If the CROs do not perform clinical trials in a satisfactory manner, breach their obligations to us, or fail to comply with regulatory requirements, the development and commercialization of our product candidates may be delayed or our development program materially and irreversibly harmed. We cannot control the amount and timing of resources these CROs devote to our program or our clinical products. If we are unable to rely on clinical data collected by our CROs, we could be required to repeat, extend the duration of, or increase the size of our clinical trials and this could significantly delay commercialization and require significantly greater expenditures.

If any of our relationships with these third-party CROs terminate, we may not be able to enter into arrangements with alternative CROs. For example, the sponsored research agreement with Northwestern may be terminated by either party upon 60 days’ written notice to the other party. If our collaboration is delayed or terminated or our ability to continue to use the current research space is terminated as a result of conflicts of interest, we may not be able to continue our planned research projects and related clinical trials on the expected timeline and may need to spend significant time and efforts to secure alternative lab facilities and equipment. If CROs do not successfully carry out their contractual duties or obligations or meet expected deadlines, if they need to be replaced, or if the quality or accuracy of the clinical data they obtain is compromised due to the failure to adhere to our clinical protocols, regulatory requirements or for other reasons, any clinical trials such CROs are associated with may be extended, delayed, or terminated, and we may not be able to obtain regulatory approval for or successfully commercialize our product candidates. As a result, we believe that our financial results and the commercial prospects for our product candidates in the subject indication would be harmed, our costs could increase and our ability to generate revenue could be delayed.

The manufacture of our product candidates, particularly those that utilize our discovery engine platform, is complex and we may encounter difficulties in production. If we or any of our third-party manufacturers encounter such difficulties, or fail to meet rigorously enforced regulatory standards, our ability to provide supply of our product candidates for preclinical studies and clinical trials or our products for patients, if approved, could be delayed or stopped, or we may be unable to maintain a commercially viable cost structure.

The processes involved in manufacturing our drug product candidates, particularly those that utilize our discovery engine platform, are complex, expensive, highly-regulated, and subject to multiple risks. Further, as product candidates are developed through preclinical studies to late-stage clinical trials towards approval and commercialization, it is common that various aspects of the development program, such as manufacturing methods, are altered along the way in an effort to optimize processes and results. Such changes carry the risk that they will not achieve these intended objectives, and any of these changes could cause our product candidates to perform differently and affect the results of planned clinical trials or other future clinical trials.

In addition, the manufacturing process for any products that we may develop is subject to FDA and other comparable foreign regulatory authority approval processes and continuous oversight, and we will need to contract with manufacturers who can meet all applicable FDA and foreign regulatory authority requirements, including, for example, complying with cGMPs, on an ongoing basis. If we or our third-party manufacturers are unable to reliably produce products to specifications acceptable to the FDA or other regulatory authorities, we may not obtain or maintain the approvals we need to commercialize such products. Even if we obtain regulatory approval for any of our product candidates, there is no assurance that either we or our contract manufacturers will be able to manufacture the approved product to specifications acceptable to the FDA or other regulatory authorities, to produce it in sufficient quantities to meet the requirements for the potential launch of the product, or to meet potential future demand. Any of these challenges could delay completion of clinical trials, require bridging clinical trials or the repetition of one or more clinical trials, increase clinical study costs, delay approval of our product candidate, impair commercialization efforts, increase our cost of goods, and have an adverse effect on our business, financial condition, results of operations, and growth prospects.

We rely completely on third-party suppliers to manufacture our clinical drug supplies for our product candidates, and we intend to rely on third parties to produce preclinical, clinical, and commercial supplies of any future product candidates.

We do not currently have, nor do we plan to acquire, the infrastructure or capability to internally manufacture our clinical drug supply of our product candidates, or any future product candidates, for use in the conduct of our preclinical studies and clinical trials, and we lack the internal resources and the capability to manufacture any product candidates on a clinical or commercial scale. The facilities used by our contract manufacturers to manufacture the active pharmaceutical ingredient and final drug product must complete a pre-approval inspection by the FDA and other comparable foreign regulatory agencies to assess compliance with applicable requirements, including cGMPs, after we submit an NDA or relevant foreign regulatory submission to the applicable regulatory agency.

We do not control the manufacturing process of, and is completely dependent on, our contract manufacturers to comply with cGMPs for manufacture of both active drug substances and finished drug products. If our contract manufacturers cannot successfully manufacture material that conforms to our specifications and the strict regulatory requirements of the FDA or applicable foreign regulatory agencies, they will not be able to pass a pre-approval inspection and we would be unable to obtain regulatory approval for our product candidate. We may be required to change contract manufacturers and verify that the new contract manufacturer maintains facilities and procedures that comply with quality standards and with all applicable regulations. We will also need to verify, such as through a manufacturing comparability study, that any new manufacturing process will produce our product candidate according to the specifications previously submitted to the FDA or another regulatory authority. The delays associated with the verification of a new CMO could negatively affect our ability to develop product candidates or commercialize our products in a timely manner or within budget. In addition, we have no direct control over our contract manufacturers’ ability to maintain adequate quality control, quality assurance, and qualified personnel. Furthermore, all of our contract manufacturers are engaged with other companies to supply and/or manufacture materials or products for such companies, which exposes our manufacturers to regulatory risks for the production of such materials and products. As a result, failure to satisfy the regulatory requirements for the production of those materials and products may affect the regulatory clearance of our contract manufacturers’ facilities generally. If the FDA or an applicable foreign regulatory agency determines now or in the future that these facilities for the manufacture of our product candidates are noncompliant, we may need to find alternative manufacturing facilities, which would adversely impact our ability to develop, obtain regulatory approval for or market our product candidates. Our reliance on contract manufacturers also exposes us to the possibility that they, or third parties with access to their facilities, will have access to and may appropriate our trade secrets or other proprietary information.

We do not have long-term supply agreements in place with our contractors, and each batch of our product candidates is individually contracted under a quality and supply agreement. If we engage new contractors, such contractors must complete an inspection by the FDA and other applicable foreign regulatory agencies. We plan to continue to rely upon contract manufacturers and, potentially, collaboration partners to manufacture commercial quantities of our product candidates, if approved. Our current scale of manufacturing is adequate to support all of our needs for preclinical studies and clinical study supplies.

Risks Related to Our Intellectual Property Rights

It is difficult and expensive to protect our intellectual property rights and we cannot ensure that they will prevent third parties from competing against us. If we are unable to adequately protect our proprietary technology, or obtain and maintain issued patents that are sufficient to protect our product candidates, others could compete against us more directly by developing and commercializing products similar or identical to ours, which would have a material adverse impact on our business, results of operations, financial condition, and prospects.

Our success will depend in part,significantly on our ability to obtain and maintain intellectual property rights, bothpatent and other proprietary protection in the United States and other countries successfullyfor commercially important technology, inventions, and know-how related to our business, defend this intellectual property against third-party challenges and successfully enforce this intellectual property to prevent third-party infringement. We rely upon a combination ofour patents, trade secret protection andshould they issue, preserve the confidentiality agreements.

Our ability to protect any of our product candidatestrade secrets, and technologies from unauthorized oroperate without infringing use by third parties depends in substantial part on our ability to obtain and maintainthe valid and enforceable patents in bothand proprietary rights of third parties. We strive to protect and enhance the United Statesproprietary technologies that we believe are important to our business, including seeking patents intended to cover our products and compositions, their methods of use, and any other countries. Patent matters ininventions that are important to the biotechnology and pharmaceutical industries can be highly uncertain and involve complex legal and factual questions. Changes in the patent laws, their implementing regulations or their interpretations may diminish the valuedevelopment of our patent rights.

There can be no assurancebusiness. We also rely on trade secrets to protect aspects of our business that are not amenable to, or that we will discover or develop patentable products or processes or that patents will issue from any pendingdo not consider appropriate for, patent applications owned or licensed by us, or if issued, the breadth of such patent coverage. protection.

We do not currently have two issued U.S. patents relating to our product candidate PTI-428, one issued U.S. patent to our product candidate PTI-801, and pending patent applications directed to our other product candidates, in PTI-801, PTI-808, PTI-428, our combination therapies and our technologies. Many of our patent applications related to our CF program are in the earliest stages, including provisional patent applications, although we do have five (5)any issued patents covering early CFTR modulator compounds not currently in development.our clinical-stage product candidate YTX-7739 as a composition of matter. We cannot provide any assurances that any of our pending patent applications will lead tomature into issued patents in any particular jurisdiction and, if they do, that such patents will include claims with a scope sufficient to protect our product candidates or otherwise provide any competitive advantage. EvenThe patent application and approval process is expensive, complex, and time-consuming. We may not be able to file and prosecute all necessary or desirable patent applications at a reasonable cost or in a timely manner. It is also possible that we will fail to identify patentable aspects of our research and development output in time to obtain patent protection. If we are unable to obtain or maintain patent protection with respect to any of our proprietary products and technology we develop, our business, financial condition, results of operations, and prospects could be materially harmed.

If the scope of any patent protection we obtain is not sufficiently broad, or if issued, we cannot guarantee that claimslose any of issued patents ownedour patent protection, our ability to prevent our competitors from commercializing similar or licensed to us are or will be held valid or enforceable by the courts or, even if unchallenged, will provide us with exclusivity or commercial value for ouridentical technology and product candidates or technology or any significant protection against competitive products or prevent others from designing around our claims. Further, if we encounter delays in regulatory approvals, the period of time during which we could market our product candidates under patent protection couldwould be reduced. Our patent rights also depend on our compliance with technology and patent licenses upon which our patent rights are based and upon the validity of assignments of patent rights from consultants and other inventors that were, or are, not employed by us.adversely affected.

The patent positions of biotechnology and pharmaceutical companies, including our patent position, involve complex legal and factual questions, which in recent years have been the subject of much litigation, and, therefore, the issuance, scope, validity, enforceability, and enforceabilitycommercial value of any patent claims that we may obtain cannot be predicted with certainty. Patents, if issued, may be challenged, deemed unenforceable, invalidated,No consistent policy regarding the breadth of claims allowed in biotechnology and pharmaceutical patents has emerged to date in the United States or circumvented. U.S. patents and patent applications may also be subject to derivation or adversarial proceedings, ex parte reexamination, or inter partes review proceedings, supplemental examination and challenges in district court. Patents may be subjected to opposition, post-grant review, or comparable proceedings lodged in variousmany foreign both national and regional, patent offices. These proceedings could resultjurisdictions. Changes in either lossthe patent laws or interpretation of the patent laws in the United States and other countries may diminish the value of our patents or denial of the patent application or loss or reduction innarrow the scope of one or moreour patent protection. The laws of some foreign countries do not protect our proprietary rights to the same extent as the laws of the claims of the patent or patent application. In addition, such proceedings may be costly. Thus, any patents, should they issue, thatUnited States, and we may own or exclusively license may not provide any protection against competitors.encounter significant problems in protecting our proprietary rights in these countries.

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Patent applications are generally maintained in confidence until publication. In the United States, for example, patent applications are typically maintained in secrecy for up to 18 months after their filing. Similarly, publication of discoveries in scientific or patent literature often lags behind actual discoveries. Consequently, we cannot be certain that we were the first to file patent applications on our product candidates. There is also no assurance that all of the potentially relevant prior art relating to our patents and patent applications has been found, which could be used by a third party to challenge the validity of our patents, should they issue, or prevent a patent from issuing from a pending patent application. Any of the foregoing could harm our competitive position, business, financial condition, results of operations, and prospects.

In addition, evenMoreover, our patents, if issued, may be challenged, deemed unenforceable, invalidated, or circumvented in the United States and abroad. U.S. patents do successfully issue, third partiesand patent applications may challengealso be subject to interference, derivation, exparte reexamination, post-grant review, or inter partes review proceedings, supplemental examination and challenges in district court. Patents may also be subjected to opposition, post-grant review, or comparable proceedings lodged in various foreign, both national and regional, patent offices or courts. An adverse determination in any such patent we own or license through adversarial proceedings in the issuing offices, whichproceeding could result in the invalidation or unenforceability of some or alleither loss of the relevant patent claims. Ifor denial of the patent application, or loss or reduction in the scope of one or more of the claims of the patent or patent application, which could limit our ability to stop others from using or commercializing similar or identical technology and products, or limit the duration of the patent protection of our technology and products. In addition, such proceedings may be costly. Thus, any patents, should they issue, that we may own or exclusively license may not provide any protection against competitors. Furthermore, an adverse decision in an interference proceeding can result in a third party assertsreceiving the patent right sought by us, which in turn could affect our ability to develop, market, or otherwise commercialize our product candidates.

Furthermore, though a substantial new question of patentabilitypatent, if it were to issue, is presumed valid and enforceable, our issuance is not conclusive as to our validity or our enforceability and it may not provide us with adequate proprietary protection or competitive advantages against any claim ofcompetitors with similar products. Even if a U.S. patent we ownissues and is held to be valid and enforceable, competitors may be able to design around or license, the U.S. Patent and Trademark Office,circumvent our patents, such as using pre-existing or USPTO, may grant a request for reexamination, which may resultnewly developed technology or products in a lossnon-infringing manner. Other parties may develop and obtain patent protection for more effective technologies, designs, or methods. If these developments were to occur, they could have a material adverse effect on our business, financial condition, results of scopeoperations, and prospects.

Our ability to enforce our patent rights depends on our ability to detect infringement. It is difficult to detect infringers who do not advertise the components that are used in their products. Moreover, it may be difficult or impossible to obtain evidence of some claimsinfringement in a competitor’s or a losspotential competitor’s product. Any litigation to enforce or defend our patent rights, even if we were to prevail, could be costly and time-consuming and would divert the attention of our management and key personnel from our business operations. We may not prevail in any lawsuits that we initiate and the entire patent. The adoption of the Leahy-Smith America Invents Act,damages or the Leahy-Smith Act, on September 16, 2011, established additional opportunities for third partiesother remedies awarded if we were to invalidate U.S. patent claims, including inter partes review and post-grant review, on the basis of a lower legal standards than reexamination and additional grounds.prevail may not be commercially meaningful.

We will incur significant ongoing expenses in maintaining our patent portfolio. Should we lack the funds to maintain our patent portfolio or to enforce our rights against infringers, we could be adversely impacted. Moreover,

We may in the failurefuture co-own patent rights relating to future product candidates and our discovery engine platform with third parties. Some of any patents thatour in-licensed patent rights are, and may issue to us orin the future be, co-owned with third parties. In addition, our licensors to adequately protect our product candidates or technology could have an adverse impact on our business.

We will not be able to seek and obtain protection for our intellectual property in all jurisdictions throughoutmay co-own the world, and we may not be able to adequately enforce our intellectual propertypatent rights even in the jurisdictions where we seek protection.

Filing, prosecuting and defending patents on all of our product candidates throughout the world would be prohibitively expensive. Competitors may manufacture and sell our potential products in those foreign countries where we do not file for and obtain patent protection or where patent protection may be unavailable, not obtainable or ultimately not enforceable. Our competitors might conduct research and development activities in countries whereus in-licenses with other third parties with whom we do not have a direct relationship. Our exclusive rights to certain of these patent rights and then useare dependent, in part, on inter-institutional or other operating agreements between the information learned fromjoint owners of such activitiespatent rights, who are not parties to develop competitive products for saleour license agreements. If our licensors do not have exclusive control of the grant of licenses under any such third-party co-owners’ interest in our major commercial markets and, further,such patent rights or we are otherwise unable to secure such exclusive rights, such co-owners may be able to export otherwise infringing productslicense their rights to territories where we have patent protection but where enforcement is not as strong as that in the United States. These products may compete withother third parties, including our products in jurisdictions where we do not have any issued patentscompetitors, and our competitors could market competing products and technology. In addition, we may need the cooperation of any such co-owners of our patent claims or other intellectual property rights in order to enforce such patent rights against third parties, and such cooperation may not be effective or sufficientprovided to prevent them from so competing.

The statutory deadlines for pursuing patent protection in individual foreign jurisdictions are based on the priority date of each of our patent applications. For posenacaftor, dirocaftor and nesolicaftor, allit. Any of the statutory deadlinesforegoing could have passed.  For certain patent applications related toa material adverse effect on our CFTR modulators, their use,competitive position, business, financial conditions, results of operations, and related technology, the relevant statutory deadlines have not yet expired. Thus, for each of these patent families, particularly those that we believe provide coverage for these product candidates, we will need to decide whether and where to pursue protection outside the United States by the relevant deadlines, and we will only have the opportunity to obtain patent protection in those jurisdictions where we file for protection, and prosecute and obtain issued claims.prospects.

The laws of some foreign countries do not protect intellectual property rights to the same extent as the laws of the United States. Many companies have encountered significant problems in protecting and defending intellectual property rights in certain foreign jurisdictions. The scope and available coverage thus may vary significantly. Outside of the United States, patents we own or license, if issued, may become subject to patent opposition in the European Patent Office or similar proceedings, which may result in loss of scope of some claims or loss of the entire patent. Participation in adversarial proceedings is very complex and expensive, and may divert our management’s attention from our core business and may result in unfavorable outcomes that could adversely affect our ability to prevent third parties from competing with us.

The legal systems of some countries, particularly developing countries, do not favor the enforcement of patents and other intellectual property protection, especially those relating to biotechnology. This could make it difficult for us to stop the infringement of our patents, if obtained, or the misappropriation of our other intellectual property rights. For example, many foreign countries have compulsory licensing laws under which a patent owner must grant licenses to third parties. In addition, many countries limit the enforceability of patents against third parties, including government agencies or government contractors. In these countries, patents may provide limited or no benefit. Patent protection must ultimately be sought on a country-by-country basis, which is an expensive and time-consuming process with uncertain outcomes. Accordingly, we may choose not to seek patent protection in certain countries, and we will not have the benefit of patent protection in such countries.

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Many companies have encountered significant problems in protecting and defending intellectual property rights in foreign jurisdictions. The legal systems of certain countries, particularly certain developing countries, do not favor the enforcement of patents and other intellectual property protection, particularly those relating to biopharmaceuticals, which could make it difficult for us to stop the infringement of our patents or marketing of competing products in violation of our proprietary rights generally. For example, an April 2014 report from the Office of the United States Trade Representative identified a number of countries, including India and China, where challenges to the procurement and enforcement of patent rights have been reported. Several countries, including India and China, have been listed in the report every year since 1989. If we encounter difficulties in protecting our intellectual property rights in foreign jurisdictions, our business prospects could be substantially harmed.

Proceedings to enforce our patent rights, if obtained, in foreign jurisdictions could result in substantial costs and divert our efforts and attention from other aspects of our business, could put our patents at risk of being invalidated or interpreted narrowly, could put our patent applications at risk of not issuing and could provoke third parties to assert claims against us. We may not prevail in any lawsuits that we initiate and the damages or other remedies awarded, if any, may not be commercially meaningful. Accordingly, our efforts to enforce our intellectual property rights around the world may be inadequate to obtain a significant commercial advantage from the intellectual property that we develop or license.

Intellectual property rights do not necessarily address all potential threats to our competitive advantage.threats.

The degree of future protection afforded by our intellectual property rights is uncertain because intellectual property rights have limitations and may not adequately protect our business or permit us to maintain our competitive advantage. The following examples are illustrative:For example, we do not know whether:

any of our pending patent applications, if issued, will include claims having a scope sufficient to protect our product candidates or any other products or product candidates;

Others mayany of our pending patent applications will issue as patents at all;

we will be able to make compounds that are similar tosuccessfully commercialize our product candidates, but that are not covered by the claims of anyif approved, before our relevant patents should they issue, that expire;

we own or have exclusively licensed.

We or our licensors or strategic collaborators might not have beenwill be the first to make the inventions covered by any issued patent oreach of our patents and pending patent application that applications;

we own or have exclusively licensed.

We or our licensors or strategic collaborators might not have beenwill be the first to file patent applications covering certain of our inventions.for these inventions;

Others may independentlyothers will not develop similar or alternative technologies or duplicate that do not infringe our patents;

others will not use pre-existing technology to effectively compete against it;

any of our technologies without infringingpatents, if issued, will be found to ultimately be valid and enforceable;

any patents issued to us will provide a basis for an exclusive market for our intellectual property rights.

Our pending patent applications may not lead to issued patents.

Patents, should they issue, that we own or that we have exclusively licensed, if any, may notcommercially viable products, will provide us with any competitive advantages or maywill not be held invalid or unenforceable, as a result of legal challengeschallenged by our competitors.third parties;

Our competitors might conduct research and development activities in countries where we do not have patent rights and then use the information learned from such activities to develop competitive products for sale in our major commercial markets.

We may notwill develop additional proprietary technologies or product candidates that are patentable.separately patentable; or

Thethat our commercial activities or products will not infringe upon the patents or proprietary rights of others may have an adverse effect on our business.others.

Should any of these events occur, they could significantly harm our business, results of operations and prospects.

Recent patent reform legislation could increase the uncertainties and costs surrounding the prosecution of our patent applications and the enforcement or defense of our issued patents.

The Leahy-Smith Act includes a number of significant changes to United States patent law. These include provisions that affect the way patent applications will be prosecuted and may also affect patent litigation. Accordingly, it is not clear what, if any, impact the Leahy-Smith Act will have on the operation of our business, our current and pending patent portfolio and future intellectual property strategy. However, the Leahy-Smith Act and its implementation could increase the uncertainties and costs surrounding the prosecution of our patent applications and the enforcement or defense of our issued patents, all of which could have a material adverse effect on our business, financial condition, results of operations and financial condition.prospects.

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Obtaining and maintaining our patent protection depends on compliance with various procedural, document submission, fee payment and other requirements imposed by governmental patent agencies, and our patent protection could be reduced or eliminated for non-compliance with these requirements.

Periodic maintenance fees on any issued patent are due to be paid to the USPTO, the European Patent Office and other foreign patent agencies in several stages over the lifetime of the patent. The USPTO and various foreign national or international patent agencies require compliance with a number of procedural, documentary, fee payment and other similar provisions during the patent application process. While an inadvertent lapse can in many cases be cured by payment of a late fee or by other means in accordance with the applicable rules, there are situations in which noncompliance can result in abandonment or lapse of the patent or patent application, resulting in partial or complete loss of patent rights in the relevant jurisdiction. Non-compliance events that could result in abandonment or lapse of patent rights include, but are not limited to, failure to file non-provisional applications claiming priority to our provisional applications by the statutory deadlines, failure to timely file national and regional stage patent applications based on an international patent application, failure to respond to official actions within prescribed time limits, non-payment of fees and failure to properly legalize and submit formal documents. If we or our licensors fail to maintain the patents and patent applications covering our product candidates, our competitors might be able to enter the market, which would have a material adverse effect on our business.

The patent protection and patent prosecution for some of our product candidates is dependent or may be dependent in the future on third parties.

While we normally seek and gain the right to fully prosecute the patents relating to our product candidates, there may be times when platform technology patents or product-specific patents that relate to our product candidates are controlled by our licensors or collaboration partners. In addition, our licensors and/or licensees and/or collaboration partners may have back-up rights to prosecute patent applications in the event that we do not do so or choose not to do so, and our licensees and/or collaboration partners may have the right to assume patent prosecution rights after certain milestones are reached. If any of our licensing partners fails to appropriately prosecute and maintain patent protection for patents covering any of our product candidates, our ability to develop and commercialize those product candidates may be adversely affected and we may not be able to prevent competitors from making, using and selling competing products.

We have entered into and may in the future enter into licenses to licensed intellectual property. If we were to lose our rights to licensed intellectual property, we may not be able to continue developing or commercializing a product candidate, if approved, that relied on such licensed intellectual property.

We are currently a party to and may in the future be party to license agreements under which we are or will be granted rights to intellectual property that are important to our business. Certain of our existing and terminated license agreements impose, and we expect that future license agreements will impose on us, various diligence obligations, payment of milestones and/or royalties and other obligations, including, without limitation, patent prosecution, research and development and efforts to meet milestones under mutually-agreed development plans. If we fail to comply with our obligations in the agreements under these agreements,which we license intellectual property rights from third parties or otherwise experience disruptions to our business relationships with our licensors, we could lose license rights that are subjectimportant to a bankruptcy, the licensor may have the right to terminate the license, in which event we would not be able to continue to use the rights granted under the license, or develop or market products covered by the license. Our business could suffer, for example, if any current or future licenses terminate, if the licensors fail to abide by the terms of the license, if the licensed patents or other rights are found to be invalid or unenforceable, or if we are unable to enter into necessary licenses on acceptable terms.our business.

We have entered into license agreements with third parties and may need to obtain additional licenses from third partiesothers to advance our research or allow commercialization of our product candidates and we cannot provide any assurancesmay develop or our discovery engine platform technology. It is possible that third-party patents do not exist that mightwe may be enforced against our current product candidates or future products in the absence of such a license. We may failunable to obtain any of theseadditional licenses at a reasonable cost or on commercially reasonable terms, if at all. Even if we are able to obtain a license, it may be non-exclusive, thereby giving our competitors access to the same technologies licensed to us. In that event, we may be required to expend significant time and resources to redesign our technology, product candidates, or the methods for manufacturing them or to develop or license replacement technology.technology, all of which may not be feasible on a technical or commercial basis. If we are unable to do so, we may be unable to develop or commercialize the affected product candidates or continue to utilize our existing discovery engine platform, which could materially harm our business, financial condition, results of operations, and the third parties owning such intellectual property rights could seekprospects significantly. We cannot provide any assurances that third-party patents do not exist which might be enforced against our current technology, including our discovery engine platform technology, manufacturing methods, product candidates, or future methods or products resulting in either an injunction prohibiting our manufacture or future sales, or, with respect to our future sales, an obligation on our part to pay royalties and/or other forms of compensation.compensation to third parties, which could be significant.

LicensingIn addition, each of intellectual property involves complex legal,our license agreements, and we expect our future agreements, will impose various development, diligence, commercialization, and other obligations on it. Certain of our license agreements also require us to meet development timelines, or to exercise commercially reasonable efforts to develop and commercialize licensed products, in order to maintain the licenses. In spite of our efforts, our licensors might conclude that we have materially breached our obligations under such license agreements and might therefore terminate the license agreements, thereby removing or limiting our ability to develop and commercialize products and technology covered by these license agreements. If these in-licenses are terminated, or if the underlying patents fail to provide the intended exclusivity, competitors or other third parties would have the freedom to seek regulatory approval of, and to market, products identical to our and we may be required to cease our development and commercialization of certain of our product candidates or of our current discovery engine platform technology. Any of the foregoing could have a material adverse effect on our competitive position, business, financial conditions, results of operations, and scientific issues. Disputesprospects.

Moreover, disputes may arise between us and our licensors regarding intellectual property subject to a licenselicensing agreement, including:

the scope of rights granted under the license agreement and other interpretation-related issues;

whether and the extent to which our technology and processes infringe on intellectual property of the licensor that is not subject to the licensing agreement;

our right to sublicensethe sublicensing of patent and other rights to third parties under our collaborative development relationships;

our diligence obligations with respect tounder the use of the licensed technology in relation to our development and commercialization of our product candidates,license agreement and what activities satisfy those diligence obligations;

the inventorship and ownership of inventions and know-how resulting from the joint creation or use of intellectual property by our licensors and us and our partners; and

the priority of invention of patented technology.

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the ownership of inventions and know-how resulting from the joint creation or use of intellectual property by our licensors and us and our partners.

IfIn addition, the agreements under which we currently license intellectual property or technology from third parties are complex, and certain provisions in such agreements may be susceptible to multiple interpretations. The resolution of any contract interpretation disagreement that may arise could narrow what we believe to be the scope of our rights to the relevant intellectual property or technology, or increase what we believe to be our financial or other obligations under the relevant agreement, either of which could have a material adverse effect on our business, financial condition, results of operations, and prospects. Moreover, if disputes over intellectual property that we license now or in the futurehave licensed prevent or impair our ability to maintain our current licensing arrangements on commercially acceptable terms, we may be unable to successfully develop and commercialize the affected product candidates.candidates, which could have a material adverse effect on our business, financial conditions, results of operations, and prospects.

If we are unable to protect the confidentiality of our trade secrets, our business and competitive position may be harmed.

We may be subjectalso rely on trade secrets to litigation allegingprotect aspects of our business that are not amenable to, or that we do not consider appropriate for, patent protection. Additionally, we rely on unpatented know-how, continuing technological innovation to develop, strengthen, and maintain the proprietary and competitive position of our product candidates, which we seek to protect, in part, by confidentiality agreements with our employees and our collaborators and consultants. However, trade secrets are difficult to protect. For example, we may be required to share our trade secrets with third-party licensees, collaborators, consultants, contractors, or other advisors and we have limited control over the protection of trade secrets used by such third parties. Although we use reasonable efforts to protect our trade secrets, including by entering into confidentiality agreements, our employees, consultants, contractors, outside scientific collaborators, and other advisors may unintentionally or willfully disclose our trade secrets and proprietary information to competitors and we may not have adequate remedies for any such disclosure. Enforcing a claim that a third party illegally obtained and used, disclosed, or misappropriated any of our trade secrets is difficult, expensive, and time-consuming, and the outcome is unpredictable. Furthermore, we may not obtain these agreements in all circumstances, and the employees and consultants who are parties to these agreements may breach or violate the terms of these agreements, thus we may not have adequate remedies for any such breach or violation, and we could lose our trade secrets through such breaches or violations. In addition, trade secret laws in the United States vary, and some U.S. courts as well as courts outside the United States are sometimes less willing or unwilling to protect trade secrets. Moreover, it is possible that technology relevant to our business will be independently developed by a person that is not a party to such an agreement. Further, our trade secrets could otherwise become known or be independently discovered by our competitors or other third parties. We may not be able to prevent the unauthorized disclosure or use of our technical knowledge or trade secrets by consultants, vendors, former employees, and current employees. If our trade secrets or confidential or proprietary information is divulged to or acquired by third parties, including our competitors, our competitive position in the marketplace, business, financial condition, results of operations, and prospects may be materially adversely affected.

We may be sued for infringing the intellectual property rights of third parties or litigation or other adversarial proceedings seeking to invalidate our patents or other proprietary rights, and weothers, which may need to resort to litigation to protect or enforce our patents or other proprietary rights, all of which will be costly to defend, uncertain in its outcomeand time-consuming and may prevent or delay our product development efforts and commercialization effortsstop it from commercializing or otherwise harmincrease the costs of commercializing our business.product candidates, if approved.

Our success also will depend in part on our refraining fromability to operate without infringing, patentsmisappropriating, or otherwise violating the intellectual property ownedand proprietary rights of third parties. We cannot assure you that our business, products, and methods do not or controlled by others. Numerouswill not infringe the patents and pending applications are owned byor other intellectual property rights of third partiesparties. We may in the fields in which we are developing product candidates, both in the United States and elsewhere. It is difficult for industry participants, including us,future become party to, identify all third-party patentor threatened with, adversarial proceedings or litigation regarding intellectual property rights that may be relevantwith respect to our product candidates and technologies becausewe use in our business.

The pharmaceutical industry is characterized by extensive litigation regarding patents and other intellectual property rights. Other parties may allege that our product candidates or the use of our technologies infringe or otherwise violates patent searching is imperfect dueclaims or other intellectual property rights held by them or that we are employing their proprietary technology without authorization. As we continue to differences in terminology among patents, incomplete databasesdevelop and, the difficulty in assessing the meaningif approved, commercialize our current product candidates and scopefuture product candidates, competitors may claim that our technology infringes their intellectual property rights as part of patent claims. Moreover, because some patent applications are maintained in secrecy until the patents publish, we cannotbusiness strategies designed to impede our successful commercialization. There may be certain that third parties have not filed patent applications that cover our products and technologies. We may fail to identify relevantthird-party patents or patent applications or may identify pending patent applications of potential interest but incorrectly predict the likelihood that such patent applications may issue with claims of relevance to our technology. In addition, we may be unawarecompositions, materials, formulations, methods of one or more issued patents that would be infringed by the manufacture, sale, importation or use of a current or future product candidate, or we may incorrectly conclude that a third-party patent is invalid, unenforceable or not infringed by our activities. Additionally, pending patent applications can, subject to certain limitations, be later amended in a manner that could cover our technologies, our future products or the manufacture or methods for treatment related to the use or manufacture of our future products. Pharmaceutical companies, biotechnology companies, universities, research institutions and others may have filedproduct candidates. In particular, we are aware of an issued patent applications or have received, or may obtain, issued patents in each of the United States or elsewhere relating to aspectsand Japan that expires in 2030 that covers one of our technology, including our products, processes for testing, manufacture, formulationpreclinical assets. We do not know if we will have reasonable defenses against a claim of infringement or methods of use, including combination therapy. It is uncertain whether the issuance of any third-party patents will require us to alter our product candidates or processes, obtain licenses, or cease certain activities.

If patents issued to third parties contain blocking, dominating or conflicting claims we may choose to or, if such claims are ultimately determined to be valid, be required to obtain licenses to these patents or to develop or obtain alternative non-infringing technology and cease practicing those activities, including, potentially, the manufacture or marketing of any products deemed to infringe those patents. If any licenses are required, there can be no assurance that we will be able to obtain anya license to such licensespatent on commercially favorablereasonable terms, if at all,all. As a result, we may not be able to commercialize such asset, if approved, prior to such patent’s expiration.

Additionally, because patent applications can take many years to issue and if these licenses are not obtained, we mightmay be prevented from pursuing the developmentconfidential for 18 months or more after filing, and commercialization of certain of our potential products entirely or for certain indications. Even if a licensebecause patent claims can be obtained on acceptable terms, the rights may be non-exclusive, which could give our competitors access to the same technology or intellectual property rights licensed to us. Our failure to obtain a license to any technology that we may require to commercialize our products on favorable termsrevised before issuance, third parties may have a material adverse impact oncurrently pending patent applications which may later result in issued patents that our business, financial condition and results of operations.

Weproduct candidates may be exposed to,infringe, or threatened with, future litigation bywhich such third parties includingclaim are infringed by our competitors, havingtechnologies. If a patent or other intellectual property rights alleging that our technologies, including our products, processes for manufacture or methods of use, including combination therapy, or other proprietary technologies infringe, either literally or under the doctrine of equivalents, their intellectual property rights. Parties making claims against us may obtain injunctive or other equitable relief, which could effectively block our ability to further develop and commercializeholder believes one or more of our product candidates. Defensecandidates infringe its patent rights, the patent holder may sue us even if we have received patent protection for our technology. Moreover, we may face patent infringement claims from non-practicing entities that have no relevant drug revenue and against whom our own patent portfolio may thus have no deterrent effect.

The outcome of intellectual property litigation is subject to uncertainties that cannot be adequately quantified in advance. The coverage of patents is subject to interpretation by the courts, and the interpretation is not always uniform. If we are sued for patent infringement, we would need to demonstrate that our product candidates, products or methods either do not infringe the patent claims of the relevant patent or that the patent claims are invalid or unenforceable, and we may not be able to do this. Even if we are successful in these claims, regardlessproceedings, we may incur substantial costs and the time and attention of their merit, would involve substantial litigation expenseour management and wouldscientific personnel could be diverted in pursuing these proceedings, which could have a substantial diversion of employeematerial adverse effect on our business and operating results. In addition, we may not have sufficient resources from our business. In the event ofto bring these actions to a successful infringement orconclusion.

Patent and other types of intellectual property litigation can involve complex factual and legal questions, and their outcome is uncertain. If we are found to infringe a third party’s intellectual property rights, we could be required to obtain a license from such third party to continue developing and marketing our product candidates and technology. However, we may not be able to obtain any required license on commercially reasonable terms or at all. Even if we were to obtain a license, it could be granted on non-exclusive terms, thereby providing our competitors and other third parties access to the same technologies licensed to it. In addition, if any such claim were successfully asserted against us and we could not obtain such a license, we may havebe forced to stop or delay developing, manufacturing, selling or otherwise commercializing our product candidates. Any claim relating to intellectual property infringement that is successfully asserted against we may require us to pay substantial damages, including treble damages and attorneys’attorney’s fees if we are found to be willfully infringing another party’s patents, for willful infringement, obtain one or more licenses from third parties, paypast use of the asserted intellectual property and royalties or redesign our affected products, whichand other consideration going forward if we are forced to take a license.

Even if we are successful in these proceedings, we may be impossible or requireincur substantial costs and divert management time and monetary expenditure. We cannot predict whether any such license would be available at all or whether it would be available on commercially reasonable terms. Parties making successful claims against us may obtain injunctive or other equitable relief,attention in pursuing these proceedings, which could effectively block our ability to further develop and commercialize one or more of our product candidates. We cannot provide any assurances that third-party patents do not exist which might be enforced against our products or product candidates, resulting in either an injunction prohibiting our sales, or, with respect to our sales, an obligation on our part to pay royalties and/or other forms of compensation to third parties. Any of those occurrences would have a material adverse impacteffect on our business.

Furthermore, because of the substantial amount of discovery required in connection with intellectual property litigation, there is a risk that some of our confidential information could be compromised by disclosure during this type of litigation or any other patent litigation.it. There could also be public announcements of the results of hearings,the hearing, motions, or other interim proceedings or developments. Ifdevelopments and if securities analysts or investors perceive thesethose results to be negative, it could cause the price of shares of our common stock to decline. If we are unable to avoid infringing the patent rights of others, we may be required to seek a license, defend an infringement action, or challenge the validity of the patents in court, or redesign our products. Patent litigation is costly and time-consuming. We may not have sufficient resources to bring these actions to a successful conclusion. In addition, intellectual property litigation or claims could force us to do one or more of the following:

cease developing, selling or otherwise commercializing our product candidates;

pay substantial damages for past use of the asserted intellectual property;

obtain a license from the holder of the asserted intellectual property, which license may not be available on reasonable terms, if at all; and

in the case of trademark claims, redesign, or rename, some or all of our product candidates to avoid infringing the intellectual property rights of third parties, which may not be possible and, even if possible, could be costly and time-consuming.

Any of these risks coming to fruition could have a material adverse effect on the price of our common stock.

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We may be involved in lawsuits to protect or enforce our intellectual property, which could be time consuming, expensive and unsuccessful, and issued patents covering our product candidates could be found invalid or unenforceable if challenged in court.

Competitors may infringe our patents or the patents of our licensors, assuming patents issue from patent applications we own or license. Litigation, which could result in substantial costs to us (even if determined in our favor), may also be necessary to enforce any patents issued or licensed to us. The cost to us in initiating any litigation or other proceeding relating to patent or other proprietary rights, even if resolved in our favor, could be substantial, and litigation would divert our management’s attention. Some of our competitors may be able to sustain the costs of complex patent litigation more effectively than we can because they have substantially greater resources. Uncertainties resulting from the initiation and continuation of patent litigation or other proceedings could delay our research and development efforts and limit our ability to continue our operations. In addition, in an infringement proceeding, a court may decide that a patent of ours or our licensors is not valid, is unenforceable and/or is not infringed, or may refuse to stop the other party from using the technology at issue on the grounds that our patents do not cover the technology in question.

If we were to initiate legal proceedings against a third party to enforce a patent covering one of our product candidates or our technology, the defendant could counterclaim that our patent is invalid or unenforceable. In patent litigation in the United States and in most European countries, defendant counterclaims alleging invalidity or unenforceability are commonplace. Grounds for a validity challenge could be an alleged failure to meet any of several statutory requirements, for example, lack of novelty, obviousness or non-enablement. Grounds for an unenforceability assertion could be an allegation that someone connected with prosecution of the patent withheld relevant information from the USPTO, or made a misleading statement, during prosecution. The outcome following legal assertions of invalidity and unenforceability during patent litigation is unpredictable. With respect to the validity question, for example, we cannot be certain that there is no invalidating prior art, of which we and the patent examiner were unaware during prosecution. If a defendant were to prevail on a legal assertion of invalidity or unenforceability, we would lose at least part, and perhaps all, of the patent protection on one or more of our products or certain aspects of our platform technology. Such a loss of patent protection could have a material adverse impact on our business. Patents and other intellectual property rights also will not protect our technology if competitors design around our protected technology without legally infringing our patents or other intellectual property rights.

An adverse result in any litigation or defense proceedings could put one or more of our patents at risk of being invalidated or interpreted narrowly and could put our patent applications at risk of not issuing. Any of these outcomes would not only have an adverse effect on our patent portfolio but may also have an adverse effect on our business, if we are unable to prevent the competitive activities of third parties.

Furthermore, because of the substantial amount of discovery required in connection with intellectual property litigation, there is a risk that some of our confidential information could be compromised by disclosure during this type of litigation or any other patent litigation. There could also be public announcements of the results of hearings, motions or other interim proceedings or developments. If securities analysts or investors perceive these results to be negative, it could have a material adverse effect on the price of our common stock.

If we are not able to adequately prevent disclosure of trade secrets and other proprietary information, the value of our technology and products could be significantly diminished.

We rely on trade secrets to protect technology especially where patent protection is not believed to be appropriate or obtainable or where patents have not issued. We attempt to protect our proprietary technology and processes, in part, with confidentiality agreements and assignment of invention agreements with our employees and confidentiality agreements with our consultants and certain contractors. There can be no assurance that these agreements will not be breached, that we would have adequate remedies for any breach, or that our trade secrets will not otherwise become known or be independently discovered by competitors. We may fail in certain circumstances to obtain the necessary confidentiality agreements, or their scope or term may not be sufficiently broad to protect our interests.

If our trade secrets or other intellectual property become known to our competitors, it could result in a material adverse effect on our business,operations, financial condition, and results of operations. To the extent that we or our consultants or research collaborators use intellectual property owned by others in work for us, disputes may also arise as to the rights to related or resulting know-how and inventions.prospects.

We may be subject to claims challenging the inventorship or ownership of our patents and other intellectual property.

We enter into confidentiality and intellectual property assignment agreements with our employees, consultants, outside scientific advisors,collaborators, sponsored researchers, and sponsored researchers.other advisors. These agreements generally provide that inventions conceived by the party in the course of rendering services to us will be our exclusive property. However, these agreements may not be honored and may not effectively assign intellectual property rights to us. Moreover,The assignment of intellectual property rights under these agreements may not be automatic upon the creation of the intellectual property or the assignment agreements may be breached, and we may be forced to bring claims against third parties, or defend claims that they may bring against it, to determine the ownership of what we regard as our intellectual property. For example, even if we have a consulting agreement in place with an academic advisor pursuant to which such academic advisor is required to assign any inventions developed in connection with providing services to it, such academic advisor may not obtain these agreements inhave the right to assign such inventions to us, as it may conflict with his or her obligations to assign all circumstances.such intellectual property to his or her employing institution.

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Litigation may be necessary to defend against these and other claims challenging inventorship or ownership. If we fail in defending any such claims, in addition to paying monetary damages, we may lose valuable intellectual property rights, such as exclusive ownership of, or right to use, valuable intellectual property. Such an outcome could have a material adverse effect on our business. Even if we are successful in defending against such claims, litigation could result in substantial costs and be a distraction to management and other employees.

Obtaining and maintaining our patent protection depends on compliance with various procedural, document submission, fee payment, and other requirements imposed by governmental patent agencies, and our patent protection could be reduced or eliminated for non-compliance with these requirements.

Periodic maintenance fees, renewal fees, annuity fees, and various other government fees on our owned and in-licensed patents and patent applications are or will be due to be paid to the U.S. Patent and Trademark Office (“USPTO”) in several stages and various government patent agencies outside of the United States over the lifetime of such patents and patent applications and any patent rights we may own or license in the future. We have systems in place to remind us to pay these fees, and we employ outside firms to remind us or our licensors to pay annuity fees due to foreign patent agencies on our foreign patents and pending foreign patent applications. The USPTO and various foreign governmental patent agencies require compliance with a number of procedural, documentary, fee payment, and other similar provisions over the lifetime of our owned patents and applications. In some cases, an inadvertent lapse can be cured by payment of a late fee or by other means in accordance with the applicable rules. However, there are situations in which noncompliance can result in abandonment or lapse of the patent or patent application, resulting in partial or complete loss of patent rights in the relevant jurisdiction. In such an event, competitors or other third parties might be able to enter the market earlier than would otherwise have been the case and this circumstance could have a material adverse effect on our business, financial condition, results of operations, and prospects.

We may be involved in lawsuits or other proceedings to protect or enforce our intellectual property, which could be expensive, time-consuming, and unsuccessful.

Even if our patent applications are issued, competitors and other third parties may infringe, misappropriate, or otherwise violate our patents and other intellectual property rights. To counter infringement or unauthorized use, we may be required to file infringement claims, which can be expensive and time-consuming and divert the attention of our management and key personnel from our business operations.

Furthermore, many of our adversaries in these proceedings may have the ability to dedicate substantially greater resources to prosecuting these legal actions than we can. Our ability to enforce our patent rights also depends on our ability to detect infringement. It is difficult to detect infringers who do not advertise the components that are used in their products. Moreover, it may be difficult or impossible to obtain evidence of infringement in a competitor’s or potential competitor’s product.

In an infringement proceeding, a court may disagree with our allegations and refuse to stop the other party from using the technology at issue on the grounds that our patents do not cover the technology in question, or may decide that a patent of ours is invalid, unenforceable or not infringed. An adverse result in any litigation, defense or post-grant proceedings could result in one or more of our patents being invalidated or interpreted narrowly and could put our patent applications at risk of not issuing. If any of our patents, if and when issued, covering our product candidates are invalidated or found unenforceable, our financial position and results of operations would be materially and adversely impacted. We may not prevail in any lawsuits that we initiate and the damages or other remedies awarded if we were to prevail may not be commercially meaningful.

Interference proceedings provoked by third parties or brought by us may be necessary to determine the priority of inventions with respect to our patents or patent applications. An unfavorable outcome could require us to cease using the related technology or to attempt to license rights to us from the prevailing party. Our business could be harmed if the prevailing party does not offer us a license on commercially reasonable terms. Our involvement in litigation or interference proceedings may fail and, even if successful, may result in substantial costs, and distract our management and other employees. We may not be able to prevent infringement, misappropriation of, or other violations of our intellectual property rights, particularly in countries where the laws may not protect those rights as fully as in the United States.

Furthermore, because of the substantial amount of discovery required in connection with intellectual property litigation, there is a risk that some of our confidential information could be compromised by disclosure during this type of litigation. There could also be public announcements of the results of hearings, motions, or other interim proceedings or developments. If securities analysts or investors perceive these results to be negative, it could have a material adverse effect on the price of our common stock. Such litigation or proceedings could substantially increase our operating losses and reduce the resources available for development activities or any future sales, marketing, or distribution activities. We may not have sufficient financial or other resources to conduct such litigation or proceedings adequately. Some of our competitors may be able to sustain the costs of such litigation or proceedings more effectively than we can because of their greater financial resources and more mature and developed intellectual property portfolios. Uncertainties resulting from the initiation and continuation of patent litigation or other proceedings could have a material adverse effect on our ability to compete in the marketplace.

Issued patents covering our discovery engine platform and our product candidates could be found invalid or unenforceable if challenged.

If we initiated legal proceedings against a third party to enforce a patent, if and when issued, covering our discovery engine platform or one of our product candidates, the defendant could counterclaim that the patent covering our product candidate is invalid and/or unenforceable. The outcome of any such proceeding is generally unpredictable.

In patent litigation in the United States, defendant counterclaims alleging invalidity and/or unenforceability are commonplace. Grounds for a validity challenge include alleged failures to meet any of several statutory requirements, including lack of novelty, obviousness or non-enablement. Grounds for unenforceability assertions of a patent include allegations that someone connected with prosecution of the patent application that matured into the patent withheld relevant information from the USPTO, or made a misleading statement, during prosecution of the patent application. Third parties may also raise similar claims before administrative bodies in the United States or abroad, even outside the context of litigation. Such mechanisms include re-examination,inter partes review, post grant review and equivalent proceedings in foreign jurisdictions, e.g., opposition proceedings. Such proceedings could result in revocation or amendment of our patents in such a way that they no longer cover our product candidates or competitive products. The outcome following legal assertions of invalidity and unenforceability is unpredictable. With respect to validity, for example, we cannot be certain that there is no invalidating prior art, of which we and the patent examiner were unaware during prosecution. If a defendant were to prevail on a legal assertion of invalidity and/or unenforceability, we would lose at least part, and perhaps all, of the patent protection on our product candidates. Such a loss of patent protection would have a material adverse impact on our business.

We may not seek to protect our intellectual property rights in all jurisdictions throughout the world and we may not be able to adequately enforce our intellectual property rights even in the jurisdictions where we seek protection.

Filing and prosecuting patent applications, and defending patents on our discovery engine platform and product candidates in all countries and jurisdictions throughout the world would be prohibitively expensive, and our intellectual property rights in some countries outside the United States could be less extensive than those in the United States, assuming that rights are obtained in the United States. In addition, the laws of some foreign countries do not protect intellectual property rights to the same extent as federal and state laws in the United States. Consequently, we may not be able to prevent third parties from practicing our inventions in all countries outside the United States, or from selling or importing products made using our inventions in and into the United States or other jurisdictions. In addition, the statutory deadlines for pursuing patent protection in individual foreign jurisdictions are based on the priority date of each of our patent applications and we may not timely file foreign patent applications. For the patent families related to YTX-7739, as well as for many of the patent families that we own, the relevant statutory deadlines have not yet expired. Thus, for each of the patent families that we believe provides coverage for our lead product candidate, we will need to decide whether and where to pursue protection outside the United States.

Competitors may use our technologies in jurisdictions where we do not pursue and obtain patent protection to develop their own products and further, may export otherwise infringing products to territories where we have patent protection, but enforcement is not as strong as that in the United States. These products may compete with our products and our patents or other intellectual property rights may not be effective or sufficient to prevent them from competing. Even if we pursue and obtain issued patents in particular jurisdictions, our patent claims or other intellectual property rights may not be effective or sufficient to prevent third parties from so competing.

The laws of some foreign countries do not protect intellectual property rights to the same extent as the laws of the United States. Many companies have encountered significant problems in protecting and defending intellectual property rights in certain foreign jurisdictions. The legal systems of some countries, particularly developing countries, do not favor the enforcement of patents and other intellectual property protection, especially those relating to biotechnology or pharmaceuticals. This could make it difficult for us to stop the infringement of our patents, if obtained, or the misappropriation of or marketing of competing products in violation of our other intellectual property rights. For example, many foreign countries have compulsory licensing laws under which a patent owner must grant licenses to third parties. In addition, many countries limit the enforceability of patents against third parties, including government agencies or government contractors. In these countries, patents may provide limited or no benefit. Patent protection must ultimately be sought on a country-by-country basis, which is an expensive and time-consuming process with uncertain outcomes. Accordingly, we may choose not to seek patent protection in certain countries, and we will not have the benefit of patent protection in such countries.

Proceedings to enforce our patent rights in foreign jurisdictions could result in substantial costs and divert our efforts and attention from other aspects of our business, could put our patents at risk of being invalidated or interpreted narrowly, could put our patent applications at risk of not issuing, and could provoke third parties to assert claims against it. We may not prevail in any lawsuits that we initiate and the damages or other remedies awarded, if any, may not be commercially meaningful. Accordingly, our efforts to enforce our intellectual property rights around the world may be inadequate to obtain a significant commercial advantage from the intellectual property that we develop or license.

If we do not obtain additional protection under the Hatch-Waxman Act and similar foreign legislation by extending the patent terms and obtaining data exclusivity for our product candidates, our business may be materially harmed.

Patents have a limited lifespan. In the United States, if all maintenance fees are timely paid, the natural expiration of a patent is generally 20 years from our earliest U.S. non-provisional filing date in our chain of priority. Various extensions may be available, but the life of a patent, and the protection it affords, is limited. Even if patents covering our product candidates are obtained, once the patent life has expired for a product candidate, we may be open to competition from competitive medications, including generic medications. Given the amount of time required for the development, testing, and regulatory review of new product candidates, patents protecting such product candidates might expire before or shortly after such product candidates are commercialized. As a result, our patent portfolio may not provide us with sufficient rights to exclude others from commercializing product candidates similar or identical to ours.

Depending upon the timing, duration, and specifics of FDA marketing approval of our product candidates, one or more of the U.S. patents we own may be eligible for a limited patent term extension under the Drug Price Competition and Patent Term Restoration Act of 1984, referred to as the Hatch-Waxman Act. The Hatch-Waxman Act permits a patent term extension of up to five years as compensation for patent term lost during the FDA regulatory review process. A patent term extension cannot extend the remaining term of a patent beyond a total of 14 years from the date of product approval, only one patent may be extended and only those claims covering the approved drug, a method for using it, or a method for manufacturing it may be extended. However, we may not be granted an extension because of, for example, failing to apply within applicable deadlines, failing to apply prior to expiration of relevant patents or otherwise failing to satisfy applicable requirements. Moreover, the applicable time period or the scope of patent protection afforded could be less than we request. If we are unable to obtain a patent term extension or the term of any such extension is less than we request, the duration of patent protection we obtain for our product candidates may not provide us with any meaningful commercial or competitive advantage, our competitors may obtain approval of competing products earlier than they would otherwise be able to do so, and our ability to generate revenues could be materially adversely affected.

Changes in U.S. patent law could diminish the value of patents in general, thereby impairing our ability to protect our products.

As is the case with other biotechnology companies, our success is heavily dependent on intellectual property, particularly patents. Obtaining and enforcing patents in the biotechnology industry involve both technological and legal complexity, and is therefore costly, time-consuming, and inherently uncertain. In addition, the United States has recently enacted and is currently implementing wide-ranging patent reform legislation: the Leahy-Smith America Invents Act. The America Invents Act includes a number of significant changes to U.S. patent law. After March 2013, under the America Invents Act, the United States transitioned to a first-inventor-to-file system in which, assuming that other requirements for patentability are met, the first-inventor-to-file a patent application will be entitled to the patent on an invention regardless of whether a third party was the first to invent the claimed invention. The America Invents Act also includes provisions that affect the way patent applications will be prosecuted and that may also affect patent litigation. It is not yet clear what, if any, impact the America Invents Act will have on the operation of our business. However, the America Invents Act and its implementation could increase the uncertainties and costs surrounding the prosecution of our patent applications and the enforcement or defense of any patents that may issue from our patent applications, all of which could have a material adverse effect on our business and financial condition.

In addition, recent U.S. Supreme Court rulings have narrowed the scope of patent protection available in certain circumstances and weakened the rights of patent owners in certain situations. The full impact of these decisions is not yet known. For example, on March 20, 2012, in Mayo Collaborative Services, DBA Mayo Medical Laboratories, et al. v. Prometheus Laboratories, Inc., the Court held that several claims drawn to measuring drug metabolite levels from patient samples and correlating them to drug doses were not patentable subject matter. The decision appears to impact diagnostics patents that merely apply a law of nature via a series of routine steps and it has created uncertainty around the ability to obtain patent protection for certain inventions. Additionally, on June 13, 2013, in Association for Molecular Pathology v. Myriad Genetics, Inc., the Court held that claims to isolated genomic DNA are not patentable, but claims to complementary DNA molecules are patent eligible because they are not a natural product. The effect of the decision on patents for other isolated natural products is uncertain. However, on March 4, 2014, the USPTO issued a memorandum to patent examiners providing guidance for examining claims that recite laws of nature, natural phenomena or natural products under the Myriad and Prometheus decisions. This guidance did not limit the application of Myriad to DNA but rather applied the decision to other natural products.

In addition to increasing uncertainty with regard to our ability to obtain future patents, this combination of events has created uncertainty with respect to the value of patents, once obtained. Depending on these and other decisions by the U.S. Congress, the federal courts and the USPTO, the laws and regulations governing patents could change in unpredictable ways that could weaken our ability to obtain new patents or to enforce any patents that may issue in the future.

We may be subject to damages resulting from claims that weus or our employees, consultants, or consultantsadvisors have wrongfully used or disclosed alleged trade secrets of our employees’their current or consultants’ former employers or their clients. These claims may be costly to defend and if we do not successfully do so, we may be required to pay monetary damages and may lose valuable intellectual property rights or personnel.employers.

Many of ourOur employees and consultants werehave been previously or concurrently employed at universities orother biotechnology or pharmaceutical companies, including our competitors or potential competitors. We also engage advisors and consultants who are concurrently employed at universities or who perform services for other entities.

Although nowe try to ensure that our employees, consultants, and advisors do not use the proprietary information or know-how of others in their work for it, and although we are not aware of any claims against us are currently pending against it, we may be subject to claims that theseus or our employees, consultantsadvisors, or weconsultants have inadvertently or otherwise used or disclosed intellectual property, including trade secrets or other proprietary information, of their employers.a former employer or other third party. We have and may in the future also be subject to claims that an employee, advisor, or consultant performed work for us that conflicts with that person’s obligations to a third party, such as an employer, and thus, that the third party has an ownership interest in the intellectual property arising out of work performed for it. Litigation may be necessary to defend against these claims. If we fail in defending such claims, in addition to paying monetary damages, we may lose valuable intellectual property rights or personnel. A loss of key research personnel or their work product could compromise our ability to commercialize, or prevent us from commercializing, our product candidates, which could severely harm our business. Even if we are successful in defending against these claims, litigation could result in substantial costs and be a distraction to management.

Risks Related If we fail in defending such claims, in addition to Our Business Operations and Industry

Our future success depends onpaying money claims, we may lose valuable intellectual property rights or personnel. A loss of key personnel or their work product could hamper or prevent our ability to retain executives andcommercialize our product candidates, which would materially adversely affect our commercial development efforts.

We may not be successful in obtaining, through acquisitions, in-licenses or otherwise, necessary rights to attract, retain and motivate key personnel in a competitive environment for skilled biotechnology personnel.

Because of the specialized scientific nature of our business and the unique properties of our technology, our success is highly dependent upon our ability to attract and retain qualified scientific and technical personnel, consultants and advisors. We are dependent on the principal members of our scientific and management staff, particularly Ms. Meenu Chhabra, Ms. Sheila Wilson, Drs. Geoffrey Gilmartin, Benito Munoz and Marija Zecevic, who have extensive knowledge of and experience developing our technology. The loss of any of their services might significantly delaydiscovery engine platform, product candidates or prevent the achievement of our research, development and business objectives.other technologies.

We currently have rights to intellectual property, through licenses from third parties, to identify and develop our discovery engine platform technology and product candidates. Many pharmaceutical companies, biotechnology companies, and academic institutions are competing with it in the field of neurodegeneration and discovery engine platform and may needhave patents and have filed and are likely filing patent applications potentially relevant to recruit a significant number of additional personnel in order to achieve our operating goals.business. In order to avoid infringing these third party patents, we may find it necessary or prudent to obtain licenses to such patents from such third party intellectual property holders. In addition, with respect to any patents we co-own with third parties, we may require licenses to such co-owners’ interest to such patents. However, we may be unable to secure such licenses or otherwise acquire or in-license any compositions, methods of use, processes, or other intellectual property rights from third parties that we identify as necessary for our current or future product candidates and our discovery engine platform technology. The licensing or acquisition of third party intellectual property rights is a competitive area, and several more established companies may pursue our productstrategies to license or acquire third party intellectual property rights that we may consider attractive or necessary. These established companies may have a competitive advantage over it due to their size, capital resources and greater clinical development and marketing and sales plans,commercialization capabilities. In addition, companies that perceive us to be a competitor may be unwilling to assign or license rights to it. We also may be unable to license or acquire third party intellectual property rights on terms that would allow us to make an appropriate return on our investment or at all. If we are unable to successfully obtain rights to required third party intellectual property rights or maintain the existing intellectual property rights we have, we may needhave to hire additional qualified scientific personnel to perform research andabandon development and preclinical studies, as well as personnel with expertise in clinical operations, clinical testing, government regulation, compliance, manufacturing, marketing and sales,of the relevant program or product candidate, which may strain our existing managerial, operational, regulatory compliance, financial and other resources. We also rely on consultants and advisors to assist in formulating our research and development strategy and adhering to complex regulatory requirements. We face strong competition for qualified individuals from numerous pharmaceutical and biotechnology companies, universities and other research institutions, many of which have greater financial and other resources than us. There can be no assurance that we will be able to attract and retain such individuals on acceptable terms, if at all. Additionally, our facilities are located in Massachusetts, which may make attracting and retaining qualified scientific and technical personnel from outside of Massachusetts difficult. The failure to attract and retain qualified personnel, consultants and advisors could have a material adverse effect on our business, financial condition, and results of operations.

As our product candidates advance through clinical trials we may experience difficulties in managing our growth and expanding our operations, including, without limitation, managing international clinical trials.

We have limited experience in drug development. As our product candidates advance through preclinical studies and clinical trials, we will need to expand our development, regulatory and manufacturing capabilities or contract with other organizations to provide these capabilities for us. In the future, we expect to have to manage additional relationships with collaborators or partners, suppliers and other organizations, including, without limitation, international clinical trials. Our ability to manage our operations and prospects.

Numerous factors may limit any potential competitive advantage provided by our intellectual property rights.

The degree of future growth will requireprotection afforded by our intellectual property rights is uncertain because intellectual property rights have limitations, and may not adequately protect our business, provide a barrier to entry against our competitors or potential competitors, or permit us to continue to improvemaintain our operational, financial and management controls, reporting systems and procedures. Wecompetitive advantage. Moreover, if a third party has intellectual property rights that cover the practice of our technology, we may not be able to implement improvements tofully exercise or extract value from our management information and control systems in an efficient or timely manner andintellectual property rights. The following examples are illustrative:

others may discover deficiencies in existing systems and controls.

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We are exposed to potential product liability or similar claims, and insurance against these claims may not be sufficient to cover our liabilities, or may not be available to us at a reasonable rate in the future or at all.

Our business exposes us to potential liability risks that are inherent in the testing, manufacturing and marketing of human therapeutic products. Clinical trials involve the testing of product candidates on human subjects or volunteers under a research plan, and carry a risk of liability for personal injury or death to patients due to unforeseen adverse side effects, improper administration of the product candidate, or other factors. Many of these patients are already seriously ill and are therefore particularly vulnerable to further illness or death.  Our trials may include third party drugs taken with ours that could injure trial subjects for whose damages we would be liable and, even if we were not, we nevertheless may not be able to showmake products that are similar to our product candidates or proveutilize similar technology but that are not covered by the claims of the patents that we license or may own;

we, or our current or future licensors or collaborators, might not have been the first to make the inventions covered by the issued patent or pending patent application that we license or own now or in the future;

we, or our current or future licensors or collaborators, might not have been the first to file patent applications covering certain of our or their inventions;

others may independently develop similar or alternative technologies or duplicate any of our technologies without infringing our owned or licensed intellectual property rights;

it is possible that our product wascurrent or future pending owned or licensed patent applications will not a cause of the injury.lead to issued patents;

We carry clinical trial and product liability insurance. However, there can be no assurance

issued patents that we willhold rights to may be ableheld invalid or unenforceable, including as a result of legal challenges by our competitors or other third parties;

our competitors or other third parties might conduct research and development activities in countries where we do not have patent rights and then use the information learned from such activities to obtain develop competitive products for sale in our major commercial markets;

we may not develop additional proprietary technologies that are patentable;

the amountpatents of insurance necessary to cover potential claims or liabilities. We could be materially and adversely affected if we were required to pay damages or incur defense costs in connection with a claim outside the scope of indemnity or insurance coverage, if the indemnity is not performed or enforced in accordance with its terms, or ifothers may harm our liability exceeds the amount of applicable insurance. In addition, there can be no assurance that insurance, if obtained, will continue to be available on terms acceptable to us. Similar risks would exist upon the commercialization or marketing of any products by us or our collaborators.

Regardless of their merit or eventual outcome, product liability claims may result in:

decreased demand for our product;

injury to our reputation and significant negative media attention;

withdrawal of clinical trial volunteers or subjects;

costs of litigation;

distraction of management;business; and

substantial monetary awardswe may choose not to plaintiffs.file a patent in order to maintain certain trade secrets or know-how, and a third party may subsequently file a patent covering such intellectual property.

Should any of these events occur, they could significantly harm our business and results of operations.

Risks Related to Our Indebtedness

Our level of indebtedness and debt service obligations could adversely affect our financial condition and may make it more difficult for us to fund our operations.

In December 2019, we entered into a loan and security agreement with Hercules Capital, Inc. (“Hercules”) (the “Term Loan”), which was most recently amended in March 2021. The Term Loan provides up to $30.0 million of debt financing and has interest-only payments through August 1, 2021, with the option to extend an additional six months upon the drawdown following occurrence of a development milestone and an equity event as defined in the agreement. Thereafter, we are obligated to make payments that will include equal installments of principal and interest through the maturity date of January 1, 2024. As of March 31, 2021, $15.0 million was outstanding under the Term Loan.

All obligations under the Term Loan are secured by substantially all of our existing property and assets, excluding our intellectual property. This indebtedness may create additional financing risk for us, particularly if our business or prevailing financial market conditions are not conducive to paying off or refinancing our outstanding debt obligations at maturity. This indebtedness could also have important negative consequences, including the fact that:

we will need to repay our indebtedness by making payments of interest and principal, which will reduce the amount of money available to finance our operations, our research and development efforts and other general corporate activities; and

our failure to comply with the restrictive covenants in the Term Loan could result in an event of default that, if not cured or waived, would accelerate our obligation to repay this indebtedness, and Hercules could seek to enforce our security interest in the assets securing such indebtedness.

To the extent that additional debt is added to our current debt levels, the risks described above could increase.

We may not have cash available to us in an amount sufficient to enable us to make interest or principal payments on our indebtedness when due. If we do not make scheduled payments when due, or otherwise materially breaches or experiences an event of default under the Term Loan, Hercules could accelerate our total loan obligation or enforce our security interest against us.

Failure to satisfy our current and future debt obligations under the Term Loan could result in an event of default. In addition, other events, including certain events that are not entirely in our control, such as the occurrence of a material adverse event on our business, could cause an event of default to occur. As a result of the occurrence of an event of default, Hercules could accelerate all of the amounts due. In the event of an acceleration of amounts due under the Term Loan, we may not have sufficient funds or may be unable to arrange for additional financing to repay our indebtedness. In addition, Hercules could seek to enforce our security interests in the assets securing such indebtedness. If we are unable to pay amounts due to Hercules upon acceleration of the Term Loan or if Hercules enforces our security interest against our assets securing our indebtedness to Hercules, our ability to continue to operate our business may be jeopardized.

We are subject to certain restrictive covenants which, if breached, could result in the acceleration of our debt under the Term Loan and have a material adverse effect on our business and financial condition.prospects.

WeThe Term Loan imposes operating and other restrictions on us. Such restrictions will affect, and in many respects limit or prohibit, our ability and the ability of any future subsidiary to, among other things:

dispose of certain assets;

engage in mergers or acquisitions;

encumber our intellectual property;

incur indebtedness or liens;

pay dividends;

make certain investments; and

engage in certain other business transactions.

These restrictive covenants may become involvedprevent us from undertaking an action that we feel is in securities class action litigation thatthe best interests of our business. In addition, if we were to breach any of these restrictive covenants, Hercules could divert management’s attention andaccelerate our indebtedness under the Term Loan or enforce our security interest against our assets, either of which would materially adversely affect our business and could subject us to significant liabilities.

The stock markets in general and the market for pharmaceutical and biotechnology companies in particular have experienced extreme volatility that has often been unrelated to the operating performance of particular companies. The trading price of our common stock has been and is likely to be highly volatile and could be subject to wide fluctuations in response to various factors, some of which are beyond our control, including limited trading volume and impact of COVID-19 on market performance. In addition to the risks described in this “Risk Factors” section of this Annual Report, market and industry factors may cause the market price and demand for our common stock to fluctuate substantially, regardless of our actual operating performance, which may limit or prevent investors from selling their shares at or above the price paid for the shares and may otherwise negatively affect the liquidity of our shares.

In the past, securities class action litigation has often been brought against a company following a decline in the market price of its securities. This risk is especially relevant for us because biotechnology and pharmaceutical companies generally experience significant stock price volatility. We may become involved in this type of litigation in the future. Any lawsuit to which we are a party, with or without merit, may result in an unfavorable judgment. We also may decide to settle lawsuits on unfavorable terms.

Any such negative outcome could result in payments of substantial damages or fines, damage to our reputation or adverse changes to our business practices. Defending against litigation is costly and time-consuming, and could divert our management’s attention and our resources. Furthermore, during the course of litigation, there could be negative public announcements of the results of hearings, motions or other interim proceedings or developments, which could have a negative effect on the market price of our stock.

We must comply with environmental laws and regulations, and failure to comply with these laws and regulations could expose us to significant liabilities.

We use hazardous chemicals and biological materials in certain aspects of our business and are subject to a variety of U.S. federal, state and local laws and regulations governing the use, generation, manufacture, distribution, storage, handling, treatment and disposal of these materials. Although we believe our safety procedures for handling and disposing of these materials and waste products comply with these laws and regulations, we cannot eliminate the risk of accidental injury or contamination from the use, manufacture, distribution, storage, handling, treatment or disposal of hazardous materials. In the event of contamination or injury, or failure to comply with environmental, occupational health and safety and export control laws and regulations, we could be held liable for any resulting damages and any such liability could exceed our assets and resources, including any available insurance.

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Our business and operations would suffer in the event of system failures.

Our internal computer systems and those of our current and future contractors and consultants are vulnerable to damage from computer viruses, unauthorized access, natural disasters, terrorism, war and telecommunication and electrical failures. While we are not aware of any such material system failure, accident or security breach to date, if such an event were to occur and cause interruptions in our operations, it could result in a material disruption of our development programs and our business operations. For example, the loss of clinical trial data from completed or future clinical trials could result in delays in our regulatory approval efforts and significantly increase our costs to recover or reproduce the data. Likewise, we rely on third parties to manufacture our product candidates and conduct clinical trials, and similar events relating to their computer systems could also have a material adverse effect on our business. To the extent that any disruption or security breach were to result in a loss of, or damage to, our data or applications, or inappropriate disclosure of confidential or proprietary information, we could incur liability and the further development and commercialization of our product candidates could be delayed.

We might not be able to utilize all or a significant portion of our net operating loss carryforwards and research and development tax credit carryforwards.

Our net operating loss, or NOL, carryforwards could expire unused and be unavailable to offset future income tax liabilities because of their limited duration or because of restrictions under U.S. tax law.  Our NOLs generated in tax years ending on or prior to December 31, 2017 are only permitted to be carried forward for 20 years under applicable U.S. tax law.  Under the Tax Cuts and Jobs Act, or the Tax At, our federal NOLs generated in tax years ending after December 31, 2017 are permitted to be carried forward indefinitely under applicable U.S. tax law. Also under the Tax Act, as modified by the CARES Act, the deductibility of federal NOLs, particularly for tax years beginning after December 31, 2020, may be limited. It is uncertain if and to what extent various states will conform to the Tax Act and the CARES Act.  As of December 31, 2019, we had federal and state NOL carryforwards of $308.8 million and $295.4 million, respectively, of which less than $0.1 million and $10.7 million begin to expire in 2026 and 2030, respectively. As of December 31, 2019, we also had federal and state research and development tax credit carryforwards of $11.6 million and $4.1 million, respectively, of which less than $0.1 million begin to expire in 2027 and 2025, respectively.

These net operating loss and tax credit carryforwards could expire unused and be unavailable to offset future income tax liabilities. In addition, under Section 382 of the Internal Revenue Code of 1986, as amended, and corresponding provisions of state law, if a corporation undergoes an “ownership change,” which is generally defined as a greater than 50% change, by value, in its equity ownership over a three-year period, the corporation’s ability to use its pre-change net operating loss carryforwardscontinue to operate our business.

Risks Related to Our Business Operations, Employee Matters and other pre-change tax attributes to offset its post-change income may be limited. We have not determined if we have experienced Section 382 ownership changes in the past and if a portion of our net operating loss and tax credit carryforwards are subject to an annual limitation under Section 382. In addition, we may experience ownership changes in the future as a result of subsequent shifts in our stock ownership, some of which may be outside of our control. If we determine that an ownership change has occurred and our ability to use our historical net operating loss and tax credit carryforwards is materially limited, it would harm our future operating results by effectively increasing our future tax obligations. We have a full valuation allowance against our net deferred tax assets.Managing Growth

Accordingly, there is a risk that due to changes under the Tax Act, an ownership change, regulatory changes or other unforeseen reasons, our existing NOLs could expire or otherwise be unavailable to offset future income tax liabilities.

We will need to significantly increase the size ofdevelop and expand our organization,company, and we may experienceencounter difficulties in managing growth.this development and expansion, which could disrupt our operations.

As of March 31, 2020,2021, we had 4246 full-time employees. We willemployees and two part-time employees, and in connection with becoming a public company, we expect to increase our number of employees and the scope of our operations. To manage our anticipated development and expansion, we must continue to implement and improve our managerial, operational, and financial systems, expand our facilities, and continue to recruit and train additional qualified personnel. Also, our management may need to substantially expanddivert a disproportionate amount of its attention away from its day-to-day activities and devote a substantial amount of time to managing these development activities. Due to our managerial, commercial, financial, manufacturing and other personnellimited resources, in order to manage our operations and prepare for the commercialization of our triple combination product, if approved. Our management and personnel systems and facilities currently in place may not be adequate to support this future growth. In addition, we may not be able to effectively manage the expansion of our operations or recruit and retaintrain additional qualified personnelpersonnel. This may result in weaknesses in our infrastructure, give rise to operational mistakes, loss of business opportunities, loss of employees, and reduced productivity among remaining employees. The physical expansion of our operations may lead to significant costs and may divert financial resources from other projects, such as the future, particularly for sales and marketing positions, due to competition for personnel among pharmaceutical businesses, and the failure to do so could have a significant negative impact ondevelopment of our future product revenues and business results. Our needcandidates. If our management is unable to effectively manage our operations, growthexpected development and various projects requires that we:

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continue the hiring and training of an effective commercial organization in anticipation of the potential approval of our triple combination product, and establish appropriate systems, policies and infrastructure to support that organization;

ensure that our consultants and other service providers successfully carry out their contractual obligations, provide high quality results, and meet expected deadlines;

continue to carry out our own contractual obligations to our licensors and other third parties; and

continue to improve our operational, financial and management controls, reporting systems and procedures.

We may be unable to successfully implement these tasks on a larger scale and, accordingly, may not achieve our development and commercialization goals.

Weexpansion, our expenses may increase more than expected, our ability to generate or increase our revenue could be reduced and we may not be able to manageimplement our business strategy. Our future financial performance and our ability to commercialize our product candidates, if approved, and compete effectively if we are unablewill depend, in part, on our ability to effectively manage the future development and expansion of our company.

Our future success depends on our ability to retain our management team and to attract, retain, and motivate qualified personnel.

Our ability to compete in the highly competitive biotechnology and biopharmaceuticals industries depends upon our ability to attract and retain highly qualified managerial, scientific, and medical personnel. In order to induce valuable employees to continue their employment with us, we have provided stock options that vest over time. The value to employees of stock options that vest over time is significantly affected by movements in our stock price that are beyond our control, and may at any time be insufficient to counteract more lucrative offers from other companies.

We are highly dependent on our management, scientific and medical personnel, including our Chief Executive Officer, Richard Peters, M.D., Ph.D. Despite our efforts to retain valuable employees, members of our management, scientific, and development teams may terminate their employment with us on short notice. The loss of the services of any of our executive officers, including Dr. Peters, other key employees and other scientific and medical advisors, and an inability to find suitable replacements could result in delays in product development and harm our business. Pursuant to their employment arrangements, each of our executive officers, and other employees may voluntarily terminate their employment at any time, with or without notice. Our success also depends on our ability to continue to attract, retain, and motivate highly skilled junior, mid-level, and senior managers as well as junior, mid-level, and senior scientific and medical personnel.

We may not be able to attract or retain qualified management and commercial, scientific and clinical personnel in the future due to the intense competition for a limited number of qualified personnel among biopharmaceutical, biotechnology, pharmaceutical, and other businesses. Many of the other pharmaceutical companies that we compete against for qualified personnel have greater financial and other resources, different risk profiles, and a longer history in the industry than we do. They also may provide more diverse opportunities and better chances for career advancement. Some of these characteristics may be more appealing to high quality candidates than what we may be able to offer. We also experience competition for the hiring of scientific personnel from universities and research institutions. If we are not ableunable to continue to attract and retain necessaryhigh quality personnel, to accomplish our business objectives,the rate and success at which we can develop and commercialize product candidates will be limited.

We face potential product liability exposure, and, if claims are brought against us, we may experience constraints that will significantly impede the achievementincur substantial liability.

The use of our development objectives, our ability to raise additional capitalproduct candidates in clinical trials and our ability to implement our business strategy.

Our industry has experienced a high rate of turnover of management personnel in recent years. We are highly dependent on the skills and leadershipsale of our management team, including Meenu Chhabra,product candidates, if approved, exposes us to the risk of product liability claims. Product liability claims might be brought against us by patients, healthcare providers, or others selling or otherwise coming into contact with our Chief Executive Officer. Our senior management may terminate their employment with us at any time. If we lose one or more members of our senior management team, our ability to successfully implement our business strategy could be seriously harmed. Replacing these employees may be difficult and may take an extended period of time because of the limited number of individuals in our industry with the breadth of skills and experience required to develop, gain regulatory approval of and commercialize products successfully. Competition to hire from this limited pool is intense, andproduct candidates. For example, we may be unablesued if any product we develop allegedly causes injury or is found to hire, train, retainbe otherwise unsuitable during product testing, manufacturing, marketing or motivate additional key personnel. sale. Any such product liability claims may include allegations of defects in manufacturing, defects in design, a failure to warn of dangers inherent in the product, including as a result of interactions with alcohol or other drugs, negligence, strict liability, and a breach of warranties. Claims could also be asserted under state consumer protection acts. If we become subject to product liability claims and cannot successfully defend itself against them, we could incur substantial liabilities. In addition, regardless of merit or eventual outcome, product liability claims may result in, among other things:

withdrawal of subjects from our clinical trials;

substantial monetary awards to patients or other claimants;

decreased demand for our product candidates or any future product candidates following marketing approval, if obtained;

damage to our reputation and exposure to adverse publicity;

increased FDA warnings on product labels;

litigation costs;

distraction of management’s attention from our primary business;

loss of revenue; and

the inability to successfully commercialize our product candidates or any future product candidates, if approved.

We do not maintain “key person”product liability insurance coverage for our clinical trials with a €5 million annual aggregate coverage limit. Nevertheless, our insurance coverage may be insufficient to reimburse us for any of our executivesexpenses or other employees.

Risks Related tolosses we may suffer. Moreover, in the Ownership of Our Common Stock

Our stock price has been and will likely continue to be volatile and an active, liquid and orderly trading market may not develop for our common stock. As a result, youfuture, we may not be able to resell your sharesmaintain insurance coverage at a reasonable cost or above your purchase price.

The market price of our common stock may fluctuate substantially as a result of many factors, some of which are beyond our control. These fluctuations could cause youin sufficient amounts to lose all or part of the value of your investment in our common stock. Factors that could cause fluctuations in the market price of our common stock include the following:

the development status ofprotect us against losses, including if insurance coverage becomes increasingly expensive. If and when we obtain marketing approval for our product candidates, and whenwe intend to expand our products receive regulatory approval or are granted special regulatory designations, or lose such designations;

insurance coverage to include the results, and the timingsale of results,commercial products; however, we may not be able to obtain this product liability insurance on commercially reasonable terms. Large judgments have been awarded in class action lawsuits based on drugs that had unanticipated side effects. The cost of our preclinical studies and clinical trials, including, without limitation, the publication or delay in publication of preliminary, interim or final results, adverse events, side effects, safety or efficacy dataany product liability litigation or other information;

proceedings, even if resolved in our favor, could be substantial, particularly in light of the support and approval, if any, that we receive from our collaboration partners, the TDN, CTN, HIT-CF and other interested parties;

performance of third parties on whom we rely to conduct preclinical studies, manage our clinical trials, and manufacture our products, product components and product candidates, including their ability to comply with regulatory requirements;

the success of, and fluctuation in, the sales of our product candidates, if approved;

our execution of our sales and marketing, manufacturing and other aspectssize of our business plan;

resultsand financial resources. A product liability claim or series of operations that vary from those of our competitors and the expectations of securities analysts and investors;

changes in expectations as to our future financial performance, including financial estimates by securities analysts and investors;

changes in expectations as to our future preclinical or clinical results or prospects, including those of securities analysts and investors;

our announcement of significant licensing or collaboration arrangements, or the termination of such arrangements;

our announcement of significant contracts, acquisitions, or capital commitments;

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announcements by our competitors of competing products, clinical data, or other initiatives, including, without limitation, those that lead to the development of a new standard of care;

announcements by third parties of significant claims or proceedings against us;

regulatory and reimbursement developments in the United States and abroad;

changes in the structure of healthcare payment systems;

future sales of our common stock or debt securities;

ability to meet minimum listing requirements of the Nasdaq Stock Market;

additions or departures of key personnel; and

general domestic and international economic conditions unrelated to our performance.

The stock market in general, and the Nasdaq Global Market and life sciences companies in particular, have experienced extreme price and volume fluctuations that have often been unrelated or disproportionate to the operating performance these companies, including very recently in connection with the ongoing COVID-19 pandemic, which has resulted in decreased stock prices for many companies notwithstanding the lack of a fundamental change in their underlying business models or prospects. Broad market and industry factors, including potentially worsening economic conditions and other adverse effects or developments relating to the ongoing COVID-19 pandemic, may negatively. These broad market factors may adversely affect the market price of our common stock, regardless of our actual operating performance. In the past, following periods of volatility in the market price of a company’s securities, securities class action litigation has often been instituted. A securities class action suitbrought against us could result in significant liabilities and, regardless of the outcome, could result in substantial costs and the diversion of our management’s attention and resources.

Although our common stock is listed on The Nasdaq Global Market, trading volume in our common stock has been limited and an active trading market for our shares may never develop or be sustained. If an active market for our common stock does not develop, you may be unable to sell your shares when you wish to sell them or at a price that you consider attractive or satisfactory. The lack of an active market may also adversely affect our ability to raise capital by selling securities in the future or impair our ability to license or acquire other product candidates, businesses or technologies using our shares as consideration.

Although we have regained compliance with the requirements for continued listing on The Nasdaq Global Market, we could in the future fail to satisfy the Nasdaq continued listing requirements and our common stock could be delisted from trading, which would adversely affect the liquidity of our common stock and our ability to access the capital markets.

Our common stock is listed on the Nasdaq Global Market. If we fail to satisfy the continued listing requirements of The Nasdaq Stock Market, or Nasdaq, such as the corporate governance requirements or the minimum closing bid price requirement, Nasdaq may take steps to delist our common stock. Such a delisting would have a negative effect on the price of our common stock and would impair the ability to sell or purchase our common stock when persons wish to do so.

On August 26, 2019, we received a letter from the Listing Qualification Department of The Nasdaq Stock Market, or the Staff, notifying us that, for the last 30 consecutive business days, our common stock had not maintained the minimum bid price requirement of $1.00 per share pursuant to Nasdaq Listing Rule 5450(a)(1).

We were provided an initial period of 180 calendar days, or until February 24, 2020, to regain compliance. On December 2, 2019, we issued a press release announcing that we received a letter dated November 27, 2019 from the Staff notifying us that we had regained compliance with the requirement of The Nasdaq Global Market to maintain a minimum bid price of $1.00 per share.

Although we have regained compliance with the Nasdaq listing requirements, Nasdaq will continue to monitor our ongoing compliance. No assurance can be given that we will meet applicable Nasdaq continued listing standards. Failure to meet applicable Nasdaq continued listing standards could result in a delisting of our common stock, which could materially reduce the liquidity of our common stock and result in a corresponding material reduction in the price of our common stock. In addition, delisting could harm our ability to raise capital through alternative financing sources on terms acceptable to us, or at all, and may result in the inability to advance our drug development programs, potential loss of confidence by investors and employees, and fewer business development opportunities.

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If securities or industry analysts do not publish research or publish inaccurate or unfavorable research about our business, our stock price and trading volume could decline.

The trading market for our common stock will depend in part on the research and reports that securities or industry analysts or investors publish about us or our business. We do not have any control over these analysts or investors. If one or more of the analysts who covers us downgrades our stock or analysts or investors publish inaccurate or unfavorable research about our business, our stock price would likely decline. If one or more of these analysts ceases coverage of us or fails to publish reports on us regularly, demand for our stock could decrease, which could cause our stock price to decline and, trading volume to decline.

A significant portion ofif we are unsuccessful in defending such a claim or claims and the resulting judgments exceed our total outstanding shares may be sold into the market. This could cause the market price ofinsurance coverage, our common stock to drop significantly, even if ourfinancial condition, business, is doing well.

Sales of a substantial number of shares of our common stock in the public market could occur at any time. If our stockholders sell, or the market believes that our stockholders intend to sell, substantial amounts of our common stock in the public market, the market price of our common stock could decline significantly. All of our outstanding shares of common stock are available for sale in the public market, subject only to the restrictions of Rule 144 under the Securities Act in the case of our affiliates.

In addition, we have filed registration statements on Form S-8 registering the issuance of shares of common stock subject to options or other equity awards issued or reserved for future issuance under our equity incentive plans. Shares registered under these registration statements are available for sale in the public market subject to vesting arrangements and exercise of options, as well as Rule 144 in the case of our affiliates.

In addition, a holder of our common stock, or their transferee, has rights, subject to some conditions, to require us to file one or more registration statements covering their shares or to include their shares in registration statements that we may file for ourselves or other stockholders. If we were to register the resale of these shares, theyprospects could be freely sold in the public market. If these additional shares are sold, or if it is believed that theymaterially adversely affected.

We will be sold, in the public market, the trading price of our common stock could decline.

Raising additional funds by issuing securities may cause dilution to existing stockholders and raising funds through lending and licensing arrangements may restrict our operations or require us to relinquish proprietary rights.

Until such time, if ever, as we can generate substantial product revenues, we expect to finance our cash needs through a combination of equity offerings, debt financings, grants and license and development agreements in connection with any collaborations. We do not have any committed external source of funds. To the extent that we raise additional capital by issuing equity securities, our existing stockholders’ ownership will be diluted, and the terms of these securities may include liquidation or other preferences that adversely affect your rights as a common stockholder. Debt financing and preferred equity financing, if available, may involve agreements that include covenants limiting or restricting our ability to take specific actions, such as incurring additional debt, making capital expenditures or declaring dividends.

If we raise additional funds through collaborations, strategic alliances or marketing, distribution or licensing arrangements with third parties, we may have to relinquish valuable rights to our technologies, future revenue streams, research programs or product candidates or grant licenses on terms that may not be favorable to us. Any debt financing that we enter into may involve covenants that restrict our operations. These restrictive covenants may include limitations on additional borrowing and specific restrictions on the use of our assets as well as prohibitions on our ability to create liens, pay dividends, redeem our stock or make investments. If we are unable to raise additional funds through equity or debt financings when needed, we may be required to delay, limit, reduce or terminate our product development or future commercialization efforts or grant rights to develop and market product candidates that we would otherwise prefer to develop and market ourselves.  

We are an emerging growth company and a smaller reporting company, andincur increased costs as a result of the reduced disclosure and governance requirements applicable to emerging growth companies and smaller reporting companies, our common stock may be less attractive to investors.

We are an emerging growthoperating as a public company, and we are taking advantage of some of the exemptions from reporting requirements that are applicable to other public companies that are not emerging growth companies, including not beingour management team will be required to comply with the auditor attestation requirements of Section 404, reduced disclosure obligations regarding executive compensation in our periodic reportsdevote substantial time to new compliance initiatives.

As a public company, and proxy statements, and exemptions from the requirements of holding a nonbinding advisory vote on executive compensation and stockholder approval of any golden parachute payments not previously approved. We may take advantage of these reporting exemptions untilparticularly after we are no longer an emerging“emerging growth company. We cannot predict if investors will find our common stock less attractive becausecompany,” we will rely on these exemptions. If some investors find our common stock less attractiveincur significant legal, accounting, and other expenses that we did not incur as a result, there may be a less active trading market for our common stock and our stock price may be more volatile. We will remain an emerging growth company until December 31, 2021.

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Even following the termination of our status as an emerging growth company, we willbe able to take advantage of the reduced disclosure requirements applicable to smaller reporting companies (as that term is defined in Rule 12b-2 of the Exchange Act) and, in particular, reduced disclosure obligations regarding executive compensation in our periodic reports and proxy statements. To the extent that we are no longer eligible to use exemptions from various reporting requirements, we may be unable to realize our anticipated cost savings from these exemptions, which could have a material adverse impact on our operating results.

If we fail to maintain proper and effective internal controls, our ability to produce accurate financial statements on a timely basis could be impaired.  

We are subject to the reporting requirements of the Securities Exchange Act of 1934, as amended,private company. In addition, the Sarbanes-Oxley Act of 2002 (the “Sarbanes-Oxley Act”) and rules subsequently implemented by the SEC and The Nasdaq Stock Market have imposed various requirements on public companies, including establishment and maintenance of effective disclosure and financial controls and corporate governance practices. Our management and other personnel will need to devote a substantial amount of time to these compliance initiatives. Moreover, these rules and regulations of The Nasdaq Global Market. will increase our legal and financial compliance costs and will make some activities more time-consuming and costly.

Pursuant to Section 404 of the Sarbanes-Oxley Act of 2002, or (“Section 404,404”), we arewill be required to perform system and process evaluation and testing offurnish a report by our management on our internal control over financial reporting, to allow our management towhich may include an attestation report on the effectiveness of our internal control over financial reporting in this Form 10-Q. However, whileissued by our independent registered public accounting firm. While we remain an “emerging growth company,” as definedcompany” or a “smaller reporting company” with less than $100 million in the Jumpstart Our Business Startups Act of 2012, or JOBS Act,annual revenues, we will not be required to include an attestation report on internal control over financial reporting issued by our independent registered public accounting firm. When we cease to be an emerging growth company,To achieve compliance with Section 404 within the prescribed period, we will be engaged in a process to document and evaluate our internal control over financial reporting, which is both costly and challenging. In this regard, we will need to continue to dedicate internal resources, potentially engage outside consultants, and adopt a detailed work plan to assess and document the adequacy of internal control over financial reporting, continue steps to improve control processes as appropriate, validate through testing that controls are functioning as documented, and implement a continuous reporting and improvement process for internal control over financial reporting. Despite our efforts, there is a risk that neither we nor our independent registered public accounting firm will be able to conclude within the prescribed timeframe that our internal control over financial reporting is effective as required by Section 404. This could result in an adverse reaction in the financial markets due to a loss of confidence in the reliability of our financial statements.

If we fail to maintain proper and effective internal controls, our ability to produce accurate and timely financial statements could be impaired, which could result in sanctions or other penalties that would harm our business.

After the completion of the Merger, we became subject to the reporting requirements of the Exchange Act, the Sarbanes-Oxley Act, and the rules and regulations of The Nasdaq Capital Market. The Sarbanes-Oxley Act requires, among other things, that we maintain effective disclosure controls and procedures and internal controls over financial reporting. Commencing with our fiscal year ending the year that the Merger is completed, we must perform system and process design evaluation and testing of the effectiveness of our internal controls over financial reporting to allow management to report on the effectiveness of our internal controls over financial reporting in our Form 10-K filing for that year, as required by Section 404 of the Sarbanes-Oxley Act. This will require that we incur substantial additional professional fees and internal costs to expand our accounting and finance functions and that we expend significant management efforts. Prior to the Merger, we had never been required to test our internal controls within a specified period and, as a result, we may experience difficulty in order to include such attestation report.meeting these reporting requirements in a timely manner.

We may in the future discover weaknesses in our system of internal financial and accounting controls and procedures that could result in a material misstatement of our financial statements. Our internal control over financial reporting will not prevent or detect all errorerrors and all fraud. A control system, no matter how well designed and operated, can provide only reasonable, not absolute, assurance that the control system’s objectives will be met. Because of the inherent limitations in all control systems, no evaluation of controls can provide absolute assurance that misstatements due to error or fraud will not occur or that all control issues and instances of fraud will be detected.

If we identify oneare not able to comply with the requirements of Section 404 of the Sarbanes-Oxley Act in a timely manner, or more material weaknesses in ourif we are unable to maintain proper and effective internal controls over financial reporting, we may not be able to produce timely and accurate financial statements. If that were to happen, our investors could lose confidence in the reliability of our reported financial statements,information, the market price of our stock could decline and we could be subject to sanctions or investigations by The Nasdaq Global Market, the SEC or other regulatory authorities.

OurIn order to satisfy our obligations as a public company, we will need to hire additional qualified accounting and financial personnel with appropriate public company experience.

As a newly public company, we will need to establish and maintain effective disclosure and financial controls and proceduresmake changes in our corporate governance practices. We will need to hire additional accounting and financial personnel with appropriate public company experience and technical accounting knowledge, and it may be difficult to recruit and maintain such personnel. Even if we are able to hire appropriate personnel, our existing operating expenses and operations will be impacted by the direct costs of their employment and the indirect consequences related to the diversion of management resources from product development efforts.

Changes in tax law could adversely affect our business and financial condition.

The rules dealing with U.S. federal, state, and local and non-U.S. taxation are constantly under review by persons involved in the legislative process, the Internal Revenue Service, the U.S. Treasury Department and other taxing authorities. Changes to tax laws or tax rulings, or changes in interpretations of existing laws (which changes may have retroactive application), could adversely affect us or holders of our common stock. These changes could subject us to additional income-based taxes and non-income taxes (such as payroll, sales, use, value-added, digital tax, net worth, property, and goods and services taxes), which in turn could materially affect our financial position and results of operations. Additionally, new, changed, modified, or newly interpreted or applied tax laws could increase our customers’ and our compliance, operating and other costs, as well as the costs of our products. In recent years, many such changes have been made, and changes are likely to continue to occur in the future. As we expand the scale of our business activities, any changes in the U.S. and non-U.S. taxation of such activities may increase our effective tax rate and harm our business, financial condition, and results of operations.

Our ability to use our net operating loss carryforwards and certain tax credit carryforwards may be subject to limitation.

As of December 31, 2020, we had federal and state net operating loss (“NOL”) carryforwards of $453.8 million and $429.9 million, respectively. Of the federal NOL carryforwards, $228.1 million begin to expire in 2026, and $225.7 million can be carried forward indefinitely. Under Section 382 of the Code changes in our ownership may limit the amount of our net operating loss carryforwards and research and development tax credit carryforwards that could be utilized annually to offset our future taxable income, if any. This limitation would generally apply in the event of a cumulative change in ownership of our company of more than 50% within a three-year period. Any such limitation may significantly reduce our ability to utilize our net operating loss carryforwards and research and development tax credit carryforwards before they expire. The completion of the Merger, together with private placements and other transactions that have occurred since our inception, may trigger such an ownership change pursuant to Section 382. Any such limitation, whether as the result of the Merger, prior private placements, sales of our common stock by our existing stockholders, or additional sales of our common stock by us after the Merger, could have a material adverse effect on our results of operations in future years. We have not yet completed a Section 382 analysis, and therefore, there can be no assurances that the NOL is already not limited

Under current law, federal NOLs incurred in tax years beginning after December 31, 2017 and before January 1, 2021 may be carried back to each of the five tax years preceding such loss, and NOLs arising in tax years beginning after December 31, 2020 may not prevent or detect all errors or actsbe carried back. Moreover, federal NOLs generated in taxable years ending after December 31, 2017, may be carried forward indefinitely, but the deductibility of fraud.

Wesuch federal NOLs may be limited to 80% of our taxable income annually for tax years beginning after December 31, 2020. NOLs generated prior to December 31, 2017, however, have a 20-year carryforward period, but are not subject to the periodic reporting requirements80% limitation.

Furthermore, our ability to utilize NOLs is conditioned upon our maintaining profitability in the future and generating U.S. federal taxable income. Since we do not know whether or when we will generate the U.S. federal taxable income necessary to utilize our remaining NOLs, these NOL carryforwards generated prior to December 31, 2017 could expire unused. Notwithstanding the foregoing discussion of NOLs, we have recorded a full valuation allowance related to our NOLs due to the uncertainty of the Exchange Act. Our disclosure controlsultimate realization of the future benefits of such NOLs.

We may acquire businesses or products, or form strategic alliances, in the future, and procedureswe may not realize the benefits of such acquisitions.

We may acquire additional businesses or products, form strategic alliances, or create joint ventures with third parties that we believe will complement or augment our existing business. If we acquire businesses with promising markets or technologies, we may not be able to realize the benefit of acquiring such businesses if we are designedunable to reasonably ensuresuccessfully integrate them with our existing operations and company culture. We may encounter numerous difficulties in developing, manufacturing, and marketing any new products resulting from a strategic alliance or acquisition that information requireddelay or prevent us from realizing their expected benefits or enhancing our business. We cannot provide assurance that, following any such acquisition, we will achieve the synergies expected in order to be disclosed by usjustify the transaction.

Proteostasis Therapeutics (“Proteostasis”) stockholders may not receive any payment on the CVRs and the CVRs may otherwise expire valueless.

Pursuant to the Contingent Value Rights Agreement,(“CVR Agreement”) for each share of Proteostasis common stock held, Proteostasis stockholders of record as of immediately prior to the effective time of the Merger (after giving effect to the exercise or settlement of any Proteostasis options or Proteostasis restricted stock units) received one contingent value right (“CVR”) entitling such holders to receive certain net proceeds, if any, derived from the grant, sale or transfer of rights to any of three specified counterparties of all or any part of Proteostasis’ intellectual property relating to its cystic fibrosis clinical programs (the “CF Assets”) completed prior to the effective time of the Merger or during the nine-month period after such effective time (a “CF Monetization”) (with any potential payment obligations continuing until the 10-year anniversary of the closing of the Merger).

A CF Monetization was not completed prior to the effective time of the Merger and each of the three specified counterparties has expressed that it is not interested in reports we filea transaction. The right of Proteostasis stockholders to receive any future payment for or submit underderive any value from the Exchange ActCVRs is accumulated and communicatedcontingent solely upon our ability to management and recorded, processed, summarized and reportedmonetize all or any part of the CF Assets through a CF Asset monetization within the time periods specified in the rulesCVR Agreement and formsthe consideration received being greater than the amounts permitted to be reimbursed to us under the CVR Agreement. If a CF Asset Monetization is not achieved within the time periods specified in the CVR Agreement or the consideration received is not greater than the amounts permitted to be reimbursed to Proteostasis, no payments will be made under the CVR Agreement, and the CVRs will expire valueless.

We have sole authority over whether and how to pursue the continued development of the SEC. We believe that any disclosure controlsCF Assets (if at all), and procedures as well as internal controls and procedures, no matter how well conceived and operated, can provideour only reasonable, not absolute, assurance thatobligations will be to reasonably cooperate with the objectivesrequests of the control system areCVR Holders’ Representative to carry out the intent and purpose of the CVR Agreement and not to terminate or intentionally negatively impact the CF Assets during the nine-month period following the effective time of the Merger.

Furthermore, the CVRs will be met. These inherent limitations include the realities that judgments in decision-making can be faulty and that breakdowns can occur because of simple error or mistake. Additionally, controls can be circumvented by the individual acts of some persons, by collusion of two or more people or by an unauthorized overrideunsecured obligations of the controls. Accordingly, becausecombined organization and all payments under the CVRs, all other obligations under the CVR Agreement and the CVRs and any rights or claims relating thereto will be subordinated in right of payment to the prior payment in full of all current or future senior obligations of the inherent limitationscombined organization.

General Risk Factors

Unfavorable global economic conditions could adversely affect our business, financial condition, or results of operations.

Our results of operations could be adversely affected by general conditions in the global economy and in the global financial markets. The recent global financial crisis caused extreme volatility and disruptions in the capital and credit markets. A severe or prolonged economic downturn, such as the recent global financial crisis, could result in a variety of risks to our control system, misstatements duebusiness, including, weakened demand for our product candidates and our ability to errorraise additional capital when needed on acceptable terms, if at all. A weak or fraud may occur and not be detected.

Operating as a public company has significantly increaseddeclining economy could also strain our costs and requiressuppliers, possibly resulting in supply disruption, or cause our managementcustomers to devote substantial time to compliance efforts.

As a public company, we are incurring and will continue to incur significant legal, accounting, insurance and other expenses that we did not incur as a private company. The Dodd-Frank Act and the Sarbanes-Oxley Act, as well as related rules implemented by the SEC and The Nasdaq Stock Market, have required changes in corporate governance practices of public companies. In addition, rules that the SEC is implementing or is required to implement pursuant to the Dodd-Frank Act are expected to require additional changes. We expect that compliance with these and other similar laws, rules and regulations, including compliance with Section 404delay making payments for our services. Any of the Sarbanes-Oxley Act, will substantially increaseforegoing could harm our expenses, including our legal and accounting costs, and make some activities more time-consuming and costlier. We also expect these laws, rules and regulations to make it more expensive for us to obtain director and officer liability insurance,business and we cannot anticipate all of the ways in which the current economic climate and financial market conditions could adversely impact our business.

We, or the third parties upon whom we depend, may be required to accept reduced policy limits and coverageadversely affected by earthquakes or incur substantially higher costs to obtain the same or similar coverage, which may make it more difficult for us to attract and retain qualified persons to serve on our board of directors or as officers. Additionally, we are currently searching for a new senior financial officer, and we expect that we may need to hire additional accounting, finance and other personnel in connection with our efforts to comply with the requirements of being a public company,natural disasters and our managementbusiness continuity and disaster recovery plans may not adequately protect us from a serious disaster.

Earthquakes or other personnel will need to devotenatural disasters could severely disrupt our operations, and have a substantial amount of time towards maintaining compliance with these requirements. These requirements may increase our legal and financial compliance costs and may make some activities more time-consuming and costlier. Although the JOBS Act may for a limited period of time somewhat lessen the cost of complying with these additional regulatory and other requirements, we nonetheless expect a continued increase in legal, accounting, insurance and certain other expenses in the future, which may negatively impactmaterial adverse effect on our business, results of operations, financial condition, and financial condition.prospects. If a natural disaster, power outage, or other event occurred that prevented us from using all or a significant portion of our headquarters, that damaged critical infrastructure, such as the manufacturing facilities of our third-party contract manufacturers and suppliers, or that otherwise disrupted operations, it may be difficult or, in certain cases, impossible for us to continue our business for a substantial period of time. The disaster recovery and business continuity plans we have in place may prove inadequate in the event of a serious disaster or similar event. We may incur substantial expenses as a result of the limited nature of our disaster recovery and business continuity plans, which, particularly when taken together with our lack of earthquake insurance, could have a material adverse effect on our business.

68Our internal computer systems, or those of our third-party CROs or other contractors or consultants, may fail or suffer security breaches, which could result in a material disruption of our product candidates’ development programs.


Anti-takeover provisionsDespite the implementation of security measures, our internal computer systems and those of our third-party CROs and other contractors and consultants are vulnerable to damage from computer viruses, unauthorized access, natural disasters, terrorism, war, and telecommunication and electrical failures. While we have not experienced any such system failure, accident, or security breach to date, if such an event were to occur and cause interruptions in our charter documentsoperations, it could discourage, delay or preventresult in a change in controlmaterial disruption of our companyprograms. For example, the loss of clinical study data for our product candidates could result in delays in our regulatory approval efforts and may affectsignificantly increase our costs to recover or reproduce the trading pricedata. To the extent that any disruption or security breach results in a loss of or damage to our data or applications or other data or applications relating to our technology or product candidates, or inappropriate disclosure of confidential or proprietary information, we could incur liabilities and the further development of our common stock.product candidates could be delayed.

Our amendedItem 2. Unregistered Sales of Equity Securities and restated certificateUse of incorporation and amended and restated by-laws and the Delaware General Corporation Law contain provisions that may enable our board of directors to resist a change in control of our company even if a change in control were to be considered favorable by you and other stockholders. These provisions:

provide that directors can be removed only for cause, and then only by a supermajority stockholder vote;

establish advance notice requirements for nominating directors and proposing matters to be voted on by stockholders at stockholder meetings;

require majority stockholder voting to effect certain amendments to our certificate of incorporation and by-laws;

create a classified board of directors whose members serve staggered three-year terms;

specify that special meetings of our stockholders can be called only by our board of directors;

prohibit stockholder action by written consent;

provide that vacancies on our board of directors may be filled only by a majority of directors then in office, even though less than a quorum;

specify that no stockholder is permitted to cumulate votes at any election of directors;

expressly authorize our board of directors to modify, alter or repeal our amended and restated by-laws, subject to any limitations set forth therein;

require supermajority votes of the holders of our common stock to amend specified provisions of our amended and restated certificate of incorporation; and

require supermajority votes of the holders of our common stock to amend our amended and restated by-laws, unless such amendments have been recommended to the stockholders, in which case only a majority vote is necessary.

In addition, we are subject to the provisions of Section 203 of the Delaware General Corporation Law. In general, Section 203 prohibits a publicly-held Delaware corporation from engaging in a “business combination” with an “interested stockholder” for a three-year period following the time that this stockholder becomes an interested stockholder, unless the business combination is approved in a prescribed manner. A “business combination” includes, among other things, a merger, asset or stock sale or other transaction resulting in a financial benefit to the interested stockholder. An “interested stockholder” is a person who, together with affiliates and associates, owns, or did own within three years prior to the determination of interested stockholder status, 15% or more of the corporation’s voting stock.Proceeds.

A Delaware corporation may “opt out” of these provisions with an express provision in its original certificate of incorporation or an express provision in its certificate of incorporation or by-laws resulting from a stockholders’ amendment approved by at least a majority of the outstanding voting shares. We have not opted out of these provisions. As a result, mergers or other takeover or change in control attempts of us may be discouraged or prevented.Not applicable.

We do not expect to pay any dividends on our common stock for the foreseeable future.

We currently expect to retain all future earnings, if any, for future operations, expansion and repayment of debt and have no current plans to pay any cash dividends to holders of our common stock for the foreseeable future. Any decision to declare and pay dividends in the future will be made at the discretion of our board of directors and will depend on, among other things, our results of operations, financial condition, cash requirements, contractual restrictions and other factors that our board of directors may deem relevant. As a result, you may not receive any return on an investment in our common stock unless you sell our common stock for a price greater than that which you paid for it.

69


Our by-laws provide that the Court of Chancery of the State of Delaware will be the exclusive forum for substantially all disputes between us and our stockholders, which could limit our stockholders’ ability to obtain a favorable judicial forum for disputes with us or our directors, officers, employees or stockholders.

Our by-laws provide that the Court of Chancery of the State of Delaware is the sole and exclusive forum for any derivative action or proceeding brought on our behalf, any action asserting a breach of fiduciary duty, any action asserting a claim against us arising pursuant to the Delaware General Corporation Law, our certificate of incorporation or our by-laws, or any action asserting a claim against us that is governed by the internal affairs doctrine. The choice of forum provision may limit a stockholder’s ability to bring a claim in a judicial forum that it finds favorable for disputes with us or our directors, officers, other employees or stockholders (including beneficial owners), which may discourage such lawsuits against us and our directors, officers, other employees or stockholders (including beneficial owners). Alternatively, if a court were to find the choice of forum provision contained in our by-laws to be inapplicable or unenforceable in an action, we may incur additional costs associated with resolving such action in other jurisdictions, which could adversely affect our business and financial condition.

Item  2.

Item 3. Defaults Upon Senior Securities.

Unregistered Sales of Equity Securities and Use of Proceeds

None.

Item  3.

Item 4. Mine Safety Disclosures.

Not applicable.

Defaults Upon Senior Securities

None.

Item 5. Other Information.

None.

Item 6. Exhibits.

Furnish the exhibits required by Item 601 of Regulation S-K (§ 229.601 of this chapter).

Item  4.Exhibit

Number

Description

10.1Fifth Amendment and Consent to Loan and Security Agreement dated as of March 29, 2021, by and among Yumanity, Inc., the lenders party thereto and Hercules Capital, Inc.
31.1*Certification of Principal Executive Officer Pursuant to Rules 13a-14(a) and 15d-14(a) under the Securities Exchange Act of 1934, as Adopted Pursuant to Section 302 of the Sarbanes-Oxley Act of 2002.Mine Safety Disclosures
31.2*Certification of Principal Financial Officer Pursuant to Rules 13a-14(a) and 15d-14(a) under the Securities Exchange Act of 1934, as Adopted Pursuant to Section 302 of the Sarbanes-Oxley Act of 2002.
32.1*Certification Pursuant to 18 U.S.C. Section 1350, as Adopted Pursuant to Section 906 of the Sarbanes-Oxley Act of 2002.
101.INSXBRL Instance Document
101.SCHXBRL Taxonomy Extension Schema Document
101.CALXBRL Taxonomy Extension Calculation Linkbase Document
101.DEFXBRL Taxonomy Extension Definition Linkbase Document
101.LABXBRL Taxonomy Extension Label Linkbase Document
101.PREXBRL Taxonomy Extension Presentation Linkbase Document

*

The certifications furnished in Exhibit 32.1 hereto are deemed to accompany this Quarterly Report on Form 10-Q and will not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended. Such certifications will not be deemed to be incorporated by reference into any filings under the Securities Act of 1933, as amended, or the Securities Exchange Act of 1934, as amended, except to the extent that the Registrant specifically incorporates it by reference.

Not applicable.

SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned thereunto duly authorized.

Company Name
Date: May 13, 2021By:

/s/ Richard Peters

Richard Peters
President, Chief Executive Officer and Principal Executive Officer
Date: May 13, 2021By:

/s/ Paulash Mohsen

Paulash Mohsen
Chief Business Officer and Principal Financial Officer

71

Item  5.

Other Information

Appointment of Principal Accounting Officer

Effective May 12, 2020, the Board of Directors appointed Michael L. Alfieri, our interim Head of Finance, to serve as our principal accounting officer, effective immediately. Mr. Alfieri is assuming the role of principal accounting officer from Meenu Chhabra, who will continue, in her role as President and Chief Executive Officer, to serve as our principal executive officer and interim principal financial officer.

Mr. Alfieri, 55, was appointed to serve as our Head of Finance through a consulting agreement between us and Danforth Advisors, LLC, a life sciences consultancy focusing on accounting and financial matters. Mr. Alfieri has served as a consultant for Danforth Advisors since September 2019. Prior to then, Mr. Alfieri served as Vice President, Finance and Principal Financial Officer of Genocea Biosciences, Inc., a biopharmaceutical company, from April 2018 through March 2019. Prior to Genocea, Mr. Alfieri served as Vice President, Finance of Radius Health, Inc., a biopharmaceutical company, from January 2017 through April 2018. Prior to Radius, Mr. Alfieri served as Corporate Controller of Merrimack Pharmaceuticals, Inc., a biopharmaceutical company from 2014 to 2017. Mr. Alfieri holds both a B.S. and a M.S. from Bentley University.

Mr. Alfieri was not appointed to serve as our principal accounting officer pursuant to any arrangements or understandings with us or with any other person, and there are no related party transactions between Mr. Alfieri and us that would require disclosure under Item 404(a) of Regulation S-K. We have not entered into any material plan, contract, arrangement or amendment with Mr. Alfieri, and no compensatory grants or awards were made to Mr. Alfieri, in connection with his appointment as our principal accounting officer.

70


Item  6.

Exhibits

 

 

 

 

Incorporated by Reference

Exhibit

No.

 

Exhibit Description

 

Form

 

File No.

 

Exhibit

No.

 

Filing Date

 

 

 

 

 

 

 

 

 

 

 

    3.1

 

Fifth Amended and Restated Certificate of Incorporation of the Registrant.

 

S-3

 

333-228529

 

3.1

 

November 23, 2018

 

 

 

 

 

 

 

 

 

 

 

    3.2

 

Second Amended and Restated By-laws of the Registrant.

 

S-1/A

 

333-208735

 

3.4

 

February 1, 2016

 

 

 

 

 

 

 

 

 

 

 

    4.1

 

Specimen Common Stock Certificate.

 

S-1/A

 

333-208735

 

4.1

 

February 1, 2016

 

 

 

 

 

 

 

 

 

 

 

    4.2

 

Third Amended and Restated Stockholders’ Agreement of the Registrant.

 

S-1/A

 

333-208735

 

4.2

 

February 1, 2016

 

 

 

 

 

 

 

 

 

 

 

    4.3

 

Form of Preferred Stock Warrant.

 

S-1

 

333-208735

 

4.3

 

December 23, 2015

 

 

 

 

 

 

 

 

 

 

 

    4.4

 

Form of Senior Indenture

 

S-3

 

333-228529

 

4.6

 

November 23, 2018

 

 

 

 

 

 

 

 

 

 

 

    4.5

 

Form of Subordinated Indenture

 

S-3

 

333-228529

 

4.7

 

November 23, 2018

 

 

 

 

 

 

 

 

 

 

 

  31.1

 

Certification of Principal Executive Officer and Interim Financial Officer pursuant to Exchange Act rules 13a-14 or 15d-14 under the Securities Exchange Act of 1934, as Adopted Pursuant to Section 302 of the Sarbanes-Oxley Act of 2002.

 

 

 

 

 

 

 

Filed herewith

 

 

 

 

 

 

 

 

 

 

 

  31.2

 

Certification of Principal Accounting Officer pursuant to Exchange Act rules 13a-14 or 15d-14 under the Securities Exchange Act of 1934, as Adopted Pursuant to Section 302 of the Sarbanes-Oxley Act of 2002.

 

 

 

 

 

 

 

Filed herewith

 

 

 

 

 

 

 

 

 

 

 

  32.1*

 

Certification of Principal Executive Officer and Interim Financial Officer and Principal Accounting Officer pursuant to 18 U.S.C. Section 1350., as Adopted Pursuant to Section 906 of the Sarbanes-Oxley Act of 2002.

 

 

 

 

 

 

 

Furnished herewith

 

 

 

 

 

 

 

 

 

 

 

101.INS

 

XBRL Instance Document.

 

 

 

 

 

 

 

Filed herewith

 

 

 

 

 

 

 

 

 

 

 

101.SCH

 

XBRL Taxonomy Extension Schema Document.

 

 

 

 

 

 

 

Filed herewith

 

 

 

 

 

 

 

 

 

 

 

101.CAL

 

XBRL Taxonomy Extension Calculation Document.

 

 

 

 

 

 

 

Filed herewith

 

 

 

 

 

 

 

 

 

 

 

101.DEF

 

XBRL Taxonomy Extension Definition Linkbase Document.

 

 

 

 

 

 

 

Filed herewith

 

 

 

 

 

 

 

 

 

 

 

101.LAB

 

XBRL Taxonomy Extension Labels Linkbase Document.

 

 

 

 

 

 

 

Filed herewith

 

 

 

 

 

 

 

 

 

 

 

101.PRE

 

XBRL Taxonomy Extension Presentation Link Document.

 

 

 

 

 

 

 

Filed herewith

 

 

 

 

 

 

 

 

 

 

 

*This certification is being furnished herewith and is not being filed for purposes of Section 18 of the Securities Exchange Act of 1934, as amended, or otherwise subject to the liability of that section, nor shall it be deemed incorporated by reference into any filing of the Registrant under the Securities Act of 1933, as amended, or Securities Exchange Act of 1934, as amended, whether made before or after the date hereof, regardless of any general incorporation language in such filing.

71


SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned thereunto duly authorized.

PROTEOSTASIS THERAPEUTICS, INC.

Date: May 15, 2020

By:

/s/ Meenu Chhabra 

Meenu Chhabra

President and Chief Executive Officer

(Principal Executive Officer and Interim Principal Financial Officer)

Date: May 15, 2020

By:

/s/ Michael L. Alfieri 

Michael L. Alfieri

Head of Finance

(Principal Accounting Officer)

72