Registrant’s telephone number, including area code: (415) ~~500-4614~~432-9270

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,” and “emerging growth company” in Rule 12b-2 of the Exchange Act.

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 ☒

Indicate by check mark whether the registrant has filed all documents and reports required to be filed by Sections 12, 13 or 15(d) of the Securities Exchange Act of 1934 subsequent to the distribution of securities under a plan confirmed by a court. Yes ☒ No ☐

As of May ~~7, 2021,~~2, 2022, the registrant had ~~20,060,268~~ 20,351,384 shares of common stock, $0.001 par value per share, outstanding.

	March 31,			December 31,			March 31,			December 31,
	2021			2020			2022			2021
	(Unaudited)						(Unaudited)
Assets
Current assets:
Cash and cash equivalents	$	68,007		$	98,183		$	54,889		$	52,432
Restricted cash		25			25			25			25
Short-term available-for-sale securities		121,618			106,446			71,197			98,288
Prepaid and other current assets		8,286			5,548			9,298			11,237
Total current assets		197,936			210,202			135,409			161,982
Property and equipment, net		161			166			138			150
Other assets		557			706			218			290
Total assets	$	198,654		$	211,074		$	135,765		$	162,422
Liabilities and stockholders’ equity
Current liabilities:
Accounts payable	$	4,521		$	2,065		$	4,421		$	6,843
Accrued expenses		3,938			6,048			8,979			10,194
Term loan, current								5,000			2,500
Total current liabilities		8,459			8,113			18,400			19,537
Term loan, non-current, net								14,473			16,898
Other non-current liability								151			30
Total liabilities								33,024			36,465
Commitments and contingencies (Note 5)
Stockholders’ equity:
Common stock		20			20			20			20
Additional paid-in capital		328,055			326,046			341,759			339,218
Accumulated other comprehensive loss		(3	)		(10	)		(256	)		(64	)
Accumulated deficit		(137,877	)		(123,095	)		(238,782	)		(213,217	)
Total stockholders’ equity		190,195			202,961			102,741			125,957
Total liabilities and stockholders’ equity	$	198,654		$	211,074		$	135,765		$	162,422

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

	Three Months Ended
	March 31,
	2022			2021
Operating expenses:
Research and development	$	19,849		$	10,131
General and administrative		5,259			4,608
Total operating expenses		25,108			14,739
Loss from operations		(25,108	)		(14,739	)
Other expenses, net		(456	)		(43	)
Net loss before tax		(25,564	)		(14,782	)
Income tax expense		(1	)		—
Net loss	$	(25,565	)	$	(14,782	)
Other comprehensive income (loss):
Unrealized loss on available-for-sale securities		(195	)		(4	)
Foreign currency translation adjustments		3			11
Total other comprehensive income (loss)	$	(192	)	$	7
Comprehensive loss	$	(25,757	)	$	(14,775	)
Net loss per share, basic and diluted	$	(1.26	)	$	(0.74	)
Weighted-average shares used to compute net loss per share, basic and diluted		20,339,416			20,010,412

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

Three Months Ended

March 31,

2021

2020

Operating expenses:

Research and development

$
10,131

$
7,778

General and administrative

4,608

2,924

Total operating expenses

14,739

10,702

Loss from operations

(14,739
)

(10,702
)
Other (expenses) income, net

(43
)

157

Net loss before tax

(14,782
)

(10,545
)
Income tax benefit

—

1

Net loss

$
(14,782
)

$
(10,544
)
Other comprehensive income (loss):

Unrealized loss on available-for-sale securities

(4
)

—

Foreign currency translation adjustments

11

—

Total other comprehensive income

$
7

$
—

Comprehensive loss

$
(14,775
)

$
(10,544
)
Net loss per share, basic and diluted

$
0.74

$
0.76

Weighted-average shares used to compute net loss per share, basic
and diluted

20,010,412

13,789,786

							Accumulated
					Additional		Other						Total
	Common Stock				Paid-in		Comprehensive			Accumulated			Stockholders’
	Shares		Amount		Capital		Loss			Deficit			Equity
Balance as of December 31, 2021		20,317,204	$	20	$	339,218	$	(64	)	$	(213,217	)	$	125,957
Issuance of common stock upon exercise of stock options		12,065		—		29		—			—			29
Issuance of common stock upon vesting of restricted stock units		22,115		—		—		—			—			—
Stock-based compensation		—		—		2,512		—			—			2,512
Net loss		—		—		—		—			(25,565	)		(25,565	)
Other comprehensive loss		—		—		—		(192	)					(192	)
Balance as of March 31, 2022		20,351,384	$	20	$	341,759	$	(256	)	$	(238,782	)	$	102,741

							Accumulated
					Additional		Other						Total
	Common Stock				Paid-in		Comprehensive			Accumulated			Stockholders’
	Shares		Amount		Capital		Loss			Deficit			Equity
Balance as of December 31, 2020		19,931,660	$	20	$	326,046	$	(10	)	$	(123,095	)	$	202,961
Issuance of common stock upon exercise of stock options		103,170		—		216		—			—			216
Stock-based compensation		—		—		1,793		—			—			1,793
Net loss		—		—		—		—			(14,782	)		(14,782	)
Other comprehensive income		—		—		—		7			—			7
Balance as of March 31, 2021		20,034,830	$	20	$	328,055	$	(3	)	$	(137,877	)	$	190,195

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

	Three Months Ended
	March 31,
	2022			2021
Cash flows from operating activities:
Net loss	$	(25,565	)	$	(14,782	)
Adjustments to reconcile net loss to net cash used in operating activities:
Stock-based compensation		2,512			1,793
Accretion of final payment fee		121			—
Amortization of premium on available-for-sale securities		118			229
Amortization of debt issuance costs		75			77
Depreciation		18			15
Changes in operating assets and liabilities:
Prepaid and other current assets		1,942			(2,726	)
Other assets		72			72
Accounts payable		(2,422	)		2,450
Accrued expenses		(1,215	)		(2,110	)
Net cash used in operating activities		(24,344	)		(14,982	)
Cash flows from investing activities:
Proceeds from maturities of available-for-sale securities		36,179			29,896
Purchases of available-for-sale securities		(9,401	)		(45,302	)
Purchases of property and equipment		(6	)		(4	)
Net cash provided by (used in) investing activities		26,772			(15,410	)
Cash flows from financing activities:
Proceeds from issuance of common stock upon stock option exercises		29			216
Net cash provided by financing activities		29			216
Net change in cash and cash equivalents, and restricted cash		2,457			(30,176	)
Cash and cash equivalents, and restricted cash at beginning of period		52,457			98,208
Cash and cash equivalents, and restricted cash at end of period	$	54,914		$	68,032
Components of cash and cash equivalents, and restricted cash:
Cash and cash equivalents	$	54,889		$	68,007
Restricted cash		25			25
Total cash and cash equivalents, and restricted cash	$	54,914		$	68,032
Supplemental disclosures of cash information:
Cash paid for interest	$	169		$	—
Cash paid for income taxes	$	—		$	154
Supplemental disclosures of noncash information:
Purchases of property and equipment included in accounts payable and accrued expenses	$	—		$	6

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

Accumulated

Additional

Other

Total

Common Stock

Paid-in

Comprehensive

Accumulated

Stockholders’

Shares

Amount

Capital

Loss

Deficit

Equity

Balance as of December 31, 2020

19,931,660

$
20

$
326,046

$
(10
)

$
(123,095
)

$
202,961

Issuance of common stock upon exercise of stock options

103,170

—

216

—

—

216

Stock-based compensation

—

—

1,793

—

—

1,793

Net loss

—

—

—

—

(14,782
)

(14,782
)
Other comprehensive income

—

—

—

7

—

7

Balance as of March 31, 2021

20,034,830

$
20

$
328,055

$
(3
)

$
(137,877
)

$
190,195

Accumulated

Additional

Other

Total

Common Stock

Paid-in

Comprehensive

Accumulated

Stockholders’

Shares

Amount

Capital

Loss

Deficit

Equity

Balance as of December 31, 2019

13,788,982

$
14

$
163,526

$
—

$
(73,596
)

$
89,944

Issuance of common stock upon exercise of stock options

4,876

—

9

—

—

9

Stock-based compensation

—

—

493

—

—

493

Net loss

—

—

—

—

(10,544
)

(10,544
)
Balance as of March 31, 2020

13,793,858

$
14

$
164,028

$
—

$
(84,140
)

$
79,902

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

Three Months Ended

March 31,

2021

2020

Cash flows from operating activities:

Net loss

$
(14,782
)

$
(10,544
)
Adjustments to reconcile net loss to net cash used in operating activities:

Depreciation

15

12

Stock-based compensation

1,793

493

Amortization of premium on available-for-sale securities

229

—

Amortization of debt issuance costs

77

—

Changes in operating assets and liabilities:

Prepaid and other current assets

(2,726
)

109

Other assets

72

—

Accounts payable

2,450

3,066

Accrued expenses

(2,110
)

(888
)
Net cash used in operating activities

(14,982
)

(7,752
)
Cash flows from investing activities:

Purchases of available-for-sale securities

(45,302
)

—

Proceeds from maturities of available-for-sale securities

29,896

—

Purchases of property and equipment

(4
)

(61
)
Net cash used in investing activities

(15,410
)

(61
)
Cash flows from financing activities:

Proceeds from issuance of common stock upon stock option exercises

216

9

Net cash provided by financing activities

216

9

Net decrease in cash and cash equivalents, and restricted cash

(30,176
)

(7,804
)
Cash and cash equivalents, and restricted cash at beginning of period

98,208

93,360

Cash and cash equivalents, and restricted cash at end of period

$
68,032

$
85,556

Components of cash and cash equivalents, and restricted cash:

Cash and cash equivalents

$
68,007

$
85,532

Restricted cash

25

24

Total cash and cash equivalents, and restricted cash

$
68,032

$
85,556

Supplemental cash flow disclosures:

Property and equipment purchases included in accounts payable and accrued expenses

$
6

$
54

Cash paid for taxes

$
154

$
—

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

89bio, Inc. (“89bio” or the “Company”) is a clinical-stage biopharmaceutical company focused on the development and commercialization of innovative therapies for the treatment of liver and cardio-metabolic diseases. The Company’s lead product candidate, ~~BIO89-100,~~pegozafermin (previously BIO89-100), a specifically engineered glycoPEGylated analog of fibroblast growth factor 21, is currently being developed for the treatment of nonalcoholic steatohepatitis and for the treatment of severe hypertriglyceridemia.

89bio ~~Inc.~~ was formed as a Delaware corporation in June 2019 ~~for the purpose of completing an initial public offering and related transactions in order~~ to carry on the business of 89Bio Ltd., which was incorporated in Israel in January 2018.

In ~~July 2020,~~March 2021, the Company ~~completed an underwritten public offering~~entered into a sales agreement (the “Sales Agreement”) with SVB Leerink LLC and Cantor Fitzgerald & Co. (the “Sales Agents”) pursuant to which it may offer and sell up to $75.0 million of ~~3,047,040~~ shares of ~~its~~the Company’s common stock, from time to time, in “at-the-market” offerings (the “ATM Facility”). The Sales Agents are entitled to compensation at a commission equal to 3.0% of the ~~public offering~~aggregate gross sales price per share sold under the Sales Agreement. In October and November 2021, the Company received aggregate proceeds of ~~$27.50 per share. The Company raised a total~~$3.3 million, net of ~~$78.2 million in net proceeds after deducting underwriting discounts and~~ commissions ~~of $5.0 million~~ and offering ~~costs~~expenses from sales of ~~approximately $0.6 million.~~

~~In September 2020, the Company completed an underwritten public offering of 3,025,000~~186,546 shares of its common stock at a ~~public offering~~weighted-average price of ~~$28.00~~$17.97 per ~~share. The Company raised a total of $79.5 million in net proceeds after deducting underwriting discounts and commissions of $4.6 million and offering costs of approximately $0.6 million.~~share pursuant to the ATM Facility. For the three months ended March 31, 2022, there were 0 sales pursuant to the ATM Facility.

The accompanying condensed consolidated financial statements have been prepared assuming the Company will continue as a going concern, which contemplates the realization of assets and liquidation of liabilities in the normal course of business. To date, the Company has not generated revenues from its activities and has incurred substantial operating losses. Management expects the Company to continue to generate substantial operating losses for the foreseeable future until it completes development of its products and seeks regulatory approvals to market such products. The Company had cash and cash equivalents and short-term available-for-sale securities of ~~$189.6~~$126.1 million as of March 31, ~~2021.~~2022.

The Company expects that its cash and cash equivalents and short-term available-for-sale securities as of March 31, ~~2021,~~2022, together with proceeds available from the Company’s term loan facility (see Note 6), and ATM Facility, will be sufficient to fund operating expenses and capital expenditure requirements for a period of at least one year from the date these unaudited condensed consolidated financial statements are filed with the Securities and Exchange Commission (“SEC”).

The accompanying interim unaudited condensed consolidated financial statements have been prepared in accordance with generally accepted accounting principles in the United States (“U.S. GAAP”) and applicable rules and regulations of the SEC regarding interim financial reporting.

The accompanying interim condensed consolidated financial statements are unaudited. The interim unaudited condensed consolidated financial statements have been prepared on the same basis as the audited consolidated financial statements as of and for the year ended December 31, ~~2020~~2021 and, in the opinion of management, reflect all adjustments, which include only normal recurring adjustments, necessary to present fairly the Company’s consolidated financial position, results of operations and comprehensive loss, and cash flows. The results of operations for the three months ended March 31, ~~2021~~2022 are not necessarily indicative of the results to be expected for the year ending December 31, ~~2021~~2022 or for any other future annual or interim period. The condensed consolidated balance sheet as of December 31, ~~2020~~2021 was derived from the audited financial statements as of that date. These condensed consolidated financial statements should be read in conjunction with the Company’s audited consolidated financial statements included in the Annual Report on Form 10-K for the year ended December 31, ~~2020,~~2021, which was filed with the SEC on March ~~25, 2021.~~24, 2022.

The accompanying condensed consolidated financial statements include the accounts of the Company and its wholly owned subsidiaries. All intercompany balances and transactions have been eliminated in consolidation.

The preparation of condensed consolidated financial statements in conformity with U.S. GAAP requires management to make estimates and assumptions that affect the reported amounts of assets and liabilities and disclosure of contingent assets and liabilities as of the date of the condensed consolidated financial statements and the reported amounts of expenses during the reporting period. Significant estimates and assumptions made in the accompanying condensed consolidated financial statements include but are not limited to the fair value of stock options and certain accrued expenses. The Company evaluates its estimates and assumptions on an ongoing basis using historical experience and other factors and adjusts those estimates and assumptions when facts and circumstances dictate. Actual results could differ from those estimates.

Financial assets and liabilities are recorded at fair value on a recurring basis in the condensed consolidated balance sheets. The carrying values of Company’s financial assets and liabilities, including cash and cash equivalents, restricted cash, prepaid and other current assets, accounts payable and accrued expenses approximate to their fair value due to the short-term nature of these instruments. The fair value of the Company’s term loan approximates its carrying value, or amortized cost, due to the prevailing market rates of interest it bears. Fair value is defined as the price that would be received to sell an asset or paid to transfer a liability (an exit price) in an orderly transaction between market participants at the reporting date. Assets and liabilities recorded at fair value are categorized based upon the level of judgment associated with the inputs used to measure their fair value. Hierarchical levels are directly related to the amount of subjectivity with the inputs to the valuation of these assets or liabilities as follows:

Level 1—Observable inputs such as unadjusted, quoted prices in active markets for identical assets or liabilities at the measurement date;

Level 2—Inputs (other than quoted prices included in Level 1) are either directly or indirectly observable inputs for similar assets or liabilities. These include quoted prices for identical or similar assets or liabilities in active markets and quoted prices for identical or similar assets or liabilities in markets that are not active; and

Level 3—Unobservable inputs that are supported by little or no market activity and that are significant to the fair value of the assets or liabilities.

The ongoing COVID-19 pandemic has disrupted and may continue to disrupt the Company’s business and delay its preclinical and clinical programs and timelines. The Company does not yet know the full extent of potential delays to clinical trials, which could prevent or delay the Company from obtaining approval for ~~BIO89-100.~~pegozafermin. The extent to which the COVID-19 pandemic may impact the Company’s future operating results and financial condition is uncertain.

The Company considers all highly liquid investments purchased with original maturities of three months or less from the purchase date to be cash equivalents. Cash equivalents consist primarily of amounts invested in money market funds, ~~and~~ commercial paper and municipal bonds that are stated at fair value.

Investments have been classified as available-for-sale and are carried at estimated fair value as determined based upon quoted market prices or pricing models for similar securities. Management determines the appropriate classification of its available-for-sale investments in debt securities at the time of purchase. Generally, investments with original maturities beyond three months at the date of purchase are classified as short-term because it is management’s intent to use the investments to fund current operations or to make them available for current operations.

Unrealized gains and losses are excluded from earnings and are reported as a component of comprehensive loss. The Company periodically evaluates whether declines in fair values of its available-for-sale securities below their book value are other-than-temporary. This evaluation consists of several qualitative and quantitative factors regarding the severity and duration of the unrealized loss as well as the Company’s ability and intent to hold the available-for-sale security until a forecasted recovery occurs. Additionally, the Company assesses whether it has plans to sell the security or it is more likely than not it will be required to sell any available-for-sale securities before recovery of its amortized cost basis. Realized gains and losses and declines in fair value judged to be other than temporary, if any, on available-for-sale securities are included in other ~~(expenses) income,~~expenses, net. The cost of investments sold is based on the specific-identification method. ~~There are no~~The Company has 0t experienced material realized gains or losses ~~on investments for~~or other-than-temporary losses in the periods presented. Interest on available-for-sale securities is included in other ~~(expenses) income, net.~~expenses, net and is not material for the periods presented.

The Company’s comprehensive loss is comprised of net loss and changes in unrealized gains or losses on available-for-sale securities and foreign currency translation adjustments.

In February 2016, the Financial Accounting Standards ~~Accounting~~ Board (the “~~FASB~~”“FASB”) issued Accounting Standards Update (“~~ASU~~”ASU”) 2016-02—Leases (“ASU 2016-02”), requiring the recognition of lease assets and liabilities on the balance sheet. The standard: (a) clarifies the definition of a lease; (b) requires a dual approach to lease classification similar to current lease classifications; and (c) causes lessees to recognize leases on the balance sheet as a lease liability with a corresponding right-of-use asset for leases with a lease-term of more than twelve months. ~~The standard is effective for public entities for fiscal years beginning after December 15, 2018 and for nonpublic entities for fiscal years beginning after December 15, 2021.~~ As an emerging growth company, ASU 2016-02 is effective for the Company for the year ending December 31, 2022 and interim periods within the year ending December 31, 2023. The Company expects to adopt ASC 842 in the fourth quarter of 2022 using the modified retrospective method with a cumulative effect adjustment, if any, to equity at the beginning of the period of adoption. The Company anticipates electing several practical expedients that permit the Company not to reassess (i) whether a contract is ~~currently evaluating~~or contains a lease, (ii) the classification of existing leases, and (iii) whether previously capitalized initial direct costs would qualify for capitalization. The Company also anticipates electing not to separate non-lease components from the associated lease components and to not to recognize lease assets and liabilities for leases with a term of 12 months or less. The Company expects to recognize an operating liability between $0.2 million to $0.3 million with a corresponding right-of-use asset in the same amount and expects no impact to equity at the beginning of ~~this standard on its consolidated financial statements and related disclosures.~~the period of adoption.

In June 2016, the FASB issued ASU 2016-13, Financial Instruments—Credit Losses (Topic 326): Measurement of Credit Losses on Financial Instruments (“ASU 2016-13”), which replaces the existing incurred loss impairment model with an expected credit loss model and requires a financial asset measured at amortized cost to be presented at the net amount expected to be collected. ~~The standard is effective for public entities for fiscal years beginning after December 15, 2019 and for nonpublic entities for fiscal years beginning after December 15, 2022.~~ As an emerging growth company, ASU 2016-13 is effective for the Company for the year ending December 31, 2023 and interim periods within that fiscal year and must be adopted using a modified retrospective approach, with certain exceptions. The Company is ~~currently~~ evaluating the impact of this standard on its consolidated financial statements and related disclosures.

The following table presents the Company’s financial assets measured at fair value on a recurring basis by level within the fair value hierarchy as of March 31, ~~2021 (in~~2022 (in thousands):

		March 31, 2021										March 31, 2022
	Valuation	Amortized		Unrealized		Unrealized					Valuation	Amortized		Unrealized		Unrealized
	Hierarchy	Cost		Gains		Losses			Fair Value		Hierarchy	Cost		Gains		Losses			Fair Value
Money market funds	Level 1	$	53,011	$	—	$	—		$	53,011	Level 1	$	32,875	$	—	$	—		$	32,875
Commercial paper	Level 2		74,420		—		(6	)		74,414	Level 2		42,363		—		(19	)		42,344
U.S. government bonds											Level 2		21,619		—		(182	)		21,437
Corporate debt securities											Level 2		1,618		—		(11	)		1,607
Agency bonds	Level 2		21,367		14		—			21,381	Level 2		6,649		—		(32	)		6,617
Corporate debt securities	Level 2		18,794		1		(9	)		18,786
Municipal bonds	Level 2		6,241		2		—			6,243	Level 2		4,986		—		(8	)		4,978
U.S. government bonds	Level 2		5,554		2		—			5,556
Non-U.S. debt securities	Level 2		2,537		—		—			2,537	Level 2		2,014		—		(6	)		2,008
Total cash equivalents and available-for-sale securities		$	181,924	$	19	$	(15	)	$	181,928		$	112,124	$	—	$	(258	)	$	111,866
Classified as:
Cash equivalents									$	60,310									$	40,669
Short-term available-for-sale securities										121,618										71,197
Total cash equivalents and available-for-sale securities									$	181,928									$	111,866

The following table summarizes the Company’s available-for-sale securities by contractual maturity as of March 31, ~~2021 (in~~2022 (in thousands):

	March 31, 2021		March 31, 2022
Within one year	$	173,388	$	110,152
After one year through two years		8,540		1,714
Total cash equivalents and available-for-sale securities	$	181,928	$	111,866

The following table presents the Company’s financial assets measured at fair value on a recurring basis by level within the fair value hierarchy as of December 31, ~~2020~~2021 (in thousands):

		December 31, 2020										December 31, 2021
	Valuation	Amortized		Unrealized		Unrealized					Valuation	Amortized		Unrealized		Unrealized
	Hierarchy	Cost		Gains		Losses			Fair Value		Hierarchy	Cost		Gains		Losses			Fair Value
Money market funds	Level 1	$	46,134	$	—	$	—		$	46,134	Level 1	$	21,477	$	—	$	—		$	21,477
Commercial paper	Level 2		76,605		—		(2	)		76,603	Level 2		59,647		—		(10	)		59,637
U.S. government bonds											Level 2		21,662		—		(42	)		21,620
Corporate debt securities											Level 2		8,776		1		(1	)		8,776
Agency bonds	Level 2		29,654		15		—			29,669	Level 2		7,747		1		(7	)		7,741
Corporate debt securities	Level 2		11,890		—		(6	)		11,884
U.S. government bonds	Level 2		7,093		—		—			7,093
Municipal bonds	Level 2		5,592		2		(1	)		5,593	Level 2		4,251		—		(4	)		4,247
U.S. treasury bills	Level 2		4,680		—		—			4,680
Agency discount securities	Level 2		200		—		—			200
Non-U.S. debt securities											Level 2		2,506		—		(1	)		2,505
Total cash equivalents and available-for-sale securities		$	181,848	$	17	$	(9	)	$	181,856		$	126,066	$	2	$	(65	)	$	126,003
Classified as:
Cash equivalents									$	75,410									$	27,715
Short-term available-for-sale securities										106,446										98,288
Total cash equivalents and available-for-sale securities									$	181,856									$	126,003

The following table summarizes the Company’s available-for-sale securities by contractual maturity as of December 31, ~~2020~~2021 (in thousands):

	December 31, 2020		December 31, 2021
Within one year	$	160,304	$	120,726
After one year through two years		21,552		5,277
Total cash equivalents and available-for-sale securities	$	181,856	$	126,003

Prepaid and other current assets consist of the following as of the periods indicated (in thousands):

Accrued expenses consist of the following as of the periods ~~indicted~~indicated (in thousands):

	March 31,		December 31,		March 31,		December 31,
	2021		2020		2022		2021
Accrued research and development expense	$	2,121	$	2,884
Accrued research and development expenses					$	6,495	$	6,195
Accrued employee and related expenses		1,067		2,552		1,562		3,168
Accrued professional and legal fees		543		453		613		495
Accrued other expenses		207		159		309		336
Total accrued expenses	$	3,938	$	6,048	$	8,979	$	10,194

In July 2021, the Company amended the lease agreement for its San Francisco office to extend the expiration of the lease from January 2022 to January 2023, with an option to renew the term for one additional year.

Future minimumleasepaymentsunder the Company’s non-cancellableoperatingleaseobligationsas of March 31, ~~2021,~~2022, are as follows ~~(in~~(in thousands):

Rent expense was ~~$73,000~~$69,000 and ~~$60,000~~$73,000 for the three months ended March 31, ~~2021~~2022 and ~~2020,~~2021, respectively.

In April 2018, the Company concurrently entered into two Asset Transfer and License Agreements (the “Teva Agreements”) with Teva Pharmaceutical Industries Ltd (“Teva”) under which it acquired certain patents and intellectual property relating to two programs: (1) Teva’s glycoPEGylated FGF21 program, including the compound TEV-47948 ~~(BIO89-100)~~(pegozafermin), a glycoPEGylated long-acting FGF21 and (2) Teva’s development program of small molecule inhibitors of ~~Fatty Acid Synthase.~~fatty acid synthase. Pursuant to the Teva Agreements, ~~the Company paid Teva an initial nonrefundable upfront payment of $6.0 million and~~ the Company could be obligated to pay Teva up to $67.5 million under each program, for a total of $135.0 million, upon the achievement of certain clinical development and commercial milestones. In addition, the Company is obligated to pay Teva tiered royalties at percentages in the low-to-mid single-digits on worldwide net sales on all products containing the Teva compounds.

The Teva Agreements can be terminated (i) by the Company without cause ~~after the first anniversary of the effective date,~~ upon 120 days’ written notice to Teva, (ii) by either party, if the other party materially breaches any of its obligations under the Teva Agreements and fails to cure such breach within 60 days after receiving notice thereof, or (iii) by either party, if a bankruptcy petition is filed against the other party and is not dismissed within 60 days. In addition, Teva can also terminate the agreement related to the Company’s glycoPEGylated FGF21 program in the event the Company, or any of its affiliates or sublicensees, challenges any of the Teva patents licensed to the Company, and the challenge is not withdrawn within 30 days of written notice from Teva.

During the three months ended March 31, 2022 and 2021, none of the development and ~~2020,~~commercial milestones were met and accordingly, there were ~~no license payment expenses~~0 milestone payments related to the Teva Agreements.

In April 2020, the Company ~~and certain of its subsidiaries~~ entered into a Loan and Security Agreement, ~~(as amended, the~~(the “Loan Agreement”) with the lenders referred to therein (the “Lenders”), and Silicon Valley Bank (“SVB”), as collateral agent. The Loan Agreement ~~provides~~provided for (i) a secured term A loan facility (the “Term A Loan Facility”) of up to $10.0 million and (ii) a secured term B loan facility (the “Term B Loan Facility”) of up to $5.0 million that became available upon the satisfaction of certain milestones, each of which iswas available to be drawn through May 31, ~~2021 (see Note 9).~~2021. The ~~Term A~~term loan is secured by certain assets of the Borrowers (as defined in the Loan ~~Facility matures on November 1, 2022, provided, that if~~Agreement), including substantially all of the ~~Term B Loan Facility is funded, the facilities instead mature on September 1, 2023. The loans will bear interest at the greater~~assets of ~~(i) 4.50% and (ii) the sum of (a) the Prime Rate as reported in The Wall Street Journal plus (b) 1.25%. As of March 31, 2021,~~ the Company, ~~had not drawn any amount under~~excluding the ~~Loan Agreement.~~Company’s intellectual property. The term loan contains customary representations, warranties, affirmative covenants and also certain restrictive covenants.

In April 2020, in connection with the execution of the Loan Agreement, the Company issued ~~Silicon Valley Bank~~SVB a warrant to purchase 25,000 shares of the Company’s common stock with a warrant exercise price of $22.06 per share that is immediately ~~exercisable.~~exercisable and expires onJune 30, 2025, as amended. The ~~initial expiration~~fair value of the warrant at the issuance date was determined by using the Black-Scholes option-pricing model and the fair value allocated to the warrant of $0.6 million met the requirements for equity classification within additional paid-in capital. Additionally, the Company incurred $0.2 million in closing costs, which together with the value of the warrants, were recorded as debt issuance costs.

In May 2021, the parties further amended the Loan Agreement (as amended, the “2021 Loan Agreement”). The 2021 Loan Agreement increased the Term A Loan Facility to up to $20.0 million, which has been fully drawn as of March 31, 2022. The Term B Loan Facility of up to $5.0 million remains available to be drawn upon on achievement of certain additional milestones, on or before September 30, 2022. The 2021 Loan Agreement provides for interest-only payments until October 1, 2022, followed by consecutive monthly payments of principal and interest starting on October 1, 2022 and continuing through September 1, 2024, the maturity date of the term loan. The interest only period may be extended to April ~~7, 2030~~1, 2023, if on or before September 20, 2022, the Company receives net cash proceeds of at least $75.0 million from the sale of its equity securities. The term loan bears interest at the greater of (i) 4.25% and (ii) the sum of (a) the Prime Rate as reported in The Wall Street Journal plus (b) 1.00%. The interest rate on the term loan was ~~changed~~4.25% at inception and 4.50% as of March 31, 2022. In addition, a final payment fee of 5% of the principal amount of the loan is due when the term loan becomes due or upon prepayment of the term loan. If the Company elects to ~~June 30, 2025~~prepay the loan, there is also a prepayment fee of between 1% and 3% of the principal amount of the term loan depending on the timing of prepayment.

In May 2021, in connection with the ~~July 2020 offering.~~execution of the 2021 Loan Agreement, the Company issued SVB a warrant to purchase 33,923 shares of the Company’s common stock with a warrant exercise price of $19.12 per share that is immediately exercisable and expires on May 28, 2031. The Company determined the fair value of the warrant at the issuance date by using the Black-Scholes option-pricing model with the following assumptions: risk-free interest rate of ~~0.75%~~1.6%, no0 dividends, expected volatility of ~~92.30%~~98.6% and expected term of 10.0 years. Upon issuance, the fair value ~~allocated to~~of the warrant of $0.6 million was recorded as a debt issuance cost and ~~classified within other assets and~~ met the requirements for equity classification within additional paid-in capital onin the ~~condensed~~ consolidated balance sheets. AnIn addition, closing costs incurred were not material. In connection with Term B Loan Facility, if funded, the Company will issue additional warrant to purchase ~~8,333~~11,305 shares of the Company’s common stock ~~will be issued in connection with the Term B Loan Facility, if funded,~~ with the exercise price ~~determined on~~at the Company’s stock price at the time of issuance.

~~Additionally,~~The 2021 Loan Agreement was accounted for as a modification to a credit facility. The debt issuance costs incurred in May 2021, including the ~~Company incurred $0.2~~fair value of the warrant, together with the remaining unamortized debt issuance costs related to the Loan Agreement of $0.4 million ~~in closing costs that~~ were recorded as ~~debt issuance costs and classified within other assets on the condensed consolidated balance sheets.~~

~~The~~ deferred assets ~~related to the debt issuance cost~~ and ~~warrant are~~ recognized on a straight-line basis as interest expense over the ~~duration~~availability of the draw period. Since all amounts under the Term A Loan ~~Agreement and~~Facility were drawn as of December 31, 2021, all debt issuance costs were reclassified as debt discount. The carrying value of the debt discount, together with the final payment fee, are recognized using the effective interest method. Interest expense is recorded within other ~~(expenses) income,~~expenses, net onin the condensed consolidated statements of operations and comprehensive loss. As

The expected repayments of ~~March 31, 2021,~~principal amount due on the ~~remaining unamortized debt issuance costs classified within~~term loan, excluding the final payment fee (which is presented as an other ~~assets~~non-current liability on the condensed consolidated balance ~~sheet is $0.5 million.~~sheets) as of March 31, 2022 are as follows (in thousands):

~~The~~In September 2019, the Company’s board of directors ~~approved~~adopted the 2019 Equity Incentive Plan (the “2019 Plan”), which also became effective in September 2019.

The Company initially reserved 2,844,193 shares of common stock for issuance under the 2019 Plan. In addition, the number of shares of common stock reserved for issuance under the 2019 Plan will automatically increase on the first day of January for a period of up to ten years ~~commencing on January 1, 2020,~~ in an amount equal to 4% of the total number of shares of the Company’s capital stock outstanding on the immediately preceding December 31, or a lesser number of shares determined by the Company’s board of directors. As of March 31, ~~2021,~~2022, there were ~~1,633,644~~948,967 shares of common stock available for issuance as future ~~option~~equity grants under the 2019 Plan.

In October 2019, the ~~Company~~Company’s board of directors adopted the 2019 Employee Stock Purchase Plan (“ESPP”), which became effective in November 2019. The Company initially reserved 225,188 shares of common stock for purchase under the ESPP. The number of shares of common stock reserved for issuance under the ESPP will automatically increase on the first day of January for a period of up to ten years in an amount equal to 1% of the total number of shares of the Company’s common stock outstanding on the immediately preceding December 31, or a lesser number of shares determined by the Company’s board of directors. Purchases ~~will be~~are accomplished through the participation of discrete offering periods and each offering is expected to be 6six months ~~long.~~in duration. For each offering period, ESPP participants will purchase shares of common stock at a price per share equal to 85% of the lesser of the fair market value of the Company’s common stock on (1) the first trading day of the applicable offering period or (2) the last trading day of the applicable offering period. ~~The first six month offering period under the ESPP commenced on January 1, 2020.~~

As of March 31, ~~2021,~~2022, there were ~~555,122~~747,582 shares of common stock available for issuance under the ESPP.

The ~~Company recorded stock-based compensation~~following table summarizes stock option activity for the ~~periods indicated as follows (in thousands):~~three months ended March 31, 2022:

Three Months Ended

March 31,

2021

2020

Research and development

$
639

$
192

General and administrative

1,154

301

Total stock-based compensation

$
1,793

$
493

						Weighted
				Weighted		Average
				Average		Remaining		Aggregate
	Number of			Exercise		Contractual		Intrinsic
	Options			Price		Term		Value
						(In years)		(In thousands)
Balance outstanding as of December 31, 2021		2,406,668		$	16.46		8.1	$	9,970
Granted		800,566			4.49
Exercised		(12,065	)		2.43
Cancelled		(69,683	)		17.49
Balance outstanding as of March 31, 2022		3,125,486		$	13.43		8.2	$	1,211
Exercisable as of March 31, 2022		1,153,770		$	12.38		7.3	$	967

The fair value of option awards granted for the periods indicated was estimated at the date of grant using a Black-Scholes option-pricing model with the following assumptions:

	Three Months Ended						Three Months Ended
	March 31,						March 31,
	2021			2020			2022			2021
Stock Options
Expected term (years)		6.1		6.0-6.1			6.0-6.1				6.1
Contractual term (years)		10.0			10.0
Expected volatility	97.5-97.6		%	86.4-87.5		%	90.6-91.0		%	97.5-97.6		%
Risk-free interest rate	0.7-0.8		%	0.5-1.5		%	1.6-1.9		%	0.7-0.8		%
Expected dividend		—			—			—			—

Pursuant to the Company’s 2019 Plan, RSUs are granted to executives and certain employees.

In February 2021 and 2022, the Company granted certain employees service-based RSUs that generally vest annually over a three-year period. The ~~following table summarizes stock option activity~~restrictions lapse over time for these service-based RSUs. In the event of termination of the holder’s continuous service to the Company, any unvested portion of the service-based RSUs are cancelled. For the three months ended March 31, ~~2021:~~

Weighted

Weighted

Average

Average

Remaining

Aggregate

Number of

Exercise

Contractual

Intrinsic

Options

Price

Term

Value

(In years)

(In thousands)

Balance outstanding as of December 31, 2020

1,898,395

$
12.79

8.60

$
25,918

Granted

538,613

23.04

Exercised

(103,170
)

2.09

Cancelled

(52,728
)

16.42

Balance outstanding as of March 31, 2021

2,281,110

15.61

8.65

$
22,657

Exercisable as of March 31, 2021

627,372

$
8.06

7.87

$
10,725

~~Restricted Stock Units (“RSUs”)~~2022 and 2021, the Company recognized $0.2 million and $0.1 million, respectively,in expense related to the service-based RSUs.

In February 2021, the Company granted ~~56,545 service based~~performance-based RSUs that vest as to its employees with a total grant date fair value of $1.3 million. The RSUs vest annually over a three-year period. The Company recognized $0.1 million of compensation expense related to the service based RSUs in the three months ended March 31, 2021.

~~In February 2021, the Company granted 61,500 performance based RSUs to certain executives,~~ one-third ~~of which vest~~ on each one-year anniversary date, subject to achievement of a development milestone and continued service to the Company. ~~The~~In February 2022, a portion of the performance-based RSUs vested upon achievement of the development milestone and satisfaction of the continued service condition. Also, in February 2022, the Company granted performance-based RSUs that vest during the performance ~~based RSUs have a total grant date fair value~~period, subject to the achievement of ~~$1.4 million. The~~certain corporate or department targets and continued service to the Company. For the three months ended March 31, 2022 and 2021, the Company recognized $0.3 million and $0.1 million, ~~of compensation~~respectively, in expense using the accelerated attribution method, related to the performance-based RSUs as it was probable that the performance ~~based RSUs in~~conditions would be met.

The following table summarizes RSU activity for the three months ended March 31, ~~2021.~~2022:

The Company recorded stock-based compensation for the periods indicated as follows (in thousands):

Basic net loss per share is computed by dividing net loss by the weighted-average number of shares of common stock outstanding for the period. Since the Company was in a loss position for all periods presented, diluted net loss per share is the same as basic net loss per share for all periods as the inclusion of all potential shares of common stock outstanding would have been anti-dilutive.

The following outstanding potentially dilutive common stock equivalents have been excluded from the calculation of diluted net loss per share for the periods ~~presented~~indicated due to their anti-dilutive effect:

	Three Months Ended				Three Months Ended
	March 31,				March 31,
	2021		2020		2022		2021
Stock options to purchase common stock		2,281,110		1,714,685		3,125,486		2,281,110
Shares available for future option grants		1,633,644		1,676,191
Unvested restricted stock units		111,728		—		632,065		111,728
Warrants to purchase common stock						58,923		—
Employee stock purchase plan		2,357		1,735		19,258		2,357
Total		4,028,839		3,392,611		3,835,732		2,395,195

In April 2021, the Company entered into an amendment to the Loan and Security Agreement with Silicon Valley Bank to extend the draw period for both the Term Loan A Facility and Term Loan B Facility to May 31, 2021.

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

Youshould read the followingdiscussionand analysisof our financialconditionand resultsof operationstogetherwith our unaudited condensed consolidatedfinancialstatementsand relatednotes and other financialinformation includedelsewherein this Quarterly Report on Form 10-Q and our consolidatedfinancialstatementsand relatednotes and other financialinformation included in our Annual Report on Form 10-K for the year ended December 31, ~~2020.~~2021. Some of the information contained in this discussion and analysis includes forward-looking statements that involve risks and uncertainties. Our actual results could differ materially from those described in or implied by these forward-looking statements. Factors that could cause or contribute to such differences include, but are not limited to, those identified below and those discussed in the section titled “Risk Factors” included elsewhere in this Quarterly Report on Form 10-Q.

We are a clinical-stage biopharmaceutical company focused on the development and commercialization of innovative therapies for the treatment of liver and cardio-metabolic diseases. Our lead product candidate, ~~BIO89-100,~~pegozafermin (previously BIO89-100), a specifically engineered glycoPEGylated analog of ~~FGF21,~~fibroblast growth factor 21 (“FGF21”), is currently being developed for the treatment of ~~NASH~~nonalcoholic steatohepatitis (“NASH”) and for the treatment of ~~SHTG.~~severe hypertriglyceridemia (“SHTG”). NASH is a severe form of ~~NAFLD,~~nonalcoholic fatty liver disease, characterized by inflammation and fibrosis in the liver that can progress to cirrhosis, liver failure, ~~HCC~~hepatocellular carcinoma (“HCC”) and death. There are currently no approved products for the treatment of NASH. In ~~September 2020,~~January 2022, we announced positive topline ~~data~~results from an expansion cohort (cohort 7) of the Phase 1b/2a trial of ~~BIO89-100 in NASH. In December 2020, we initiated a paired-biopsy open-label cohort as part of the Phase 1b/2a trial~~pegozafermin in NASH ~~patients assessing histology endpoints with~~after announcing positive topline data ~~anticipated by the end of 2021. In April 2021, we announced that we received written guidance~~ from ~~the U.S. Food and Drug Administration (“FDA”) on the design of our planned~~cohorts 1 through 6 in September 2020. We also initiated a Phase 2b trial ~~ENLIVEN~~(ENLIVEN) evaluating ~~BIO89-100 for the treatment of patients with~~pegozafermin in fibrosis stage 2 or 3 NASH ~~including agreement on the use of a liquid formulation. A total of approximately 200~~ patients in June 2021. Patients will receive ~~either one of two different~~ weekly doses or ana every two-week dose of ~~BIO89-100~~pegozafermin or placebo for 24 weeks followed by a blinded extension phase of an additional 24 weeks for a total treatment period of 48 weeks. ~~The primary efficacy outcome measures at Week 24 will include~~We are making good progress in ENLIVEN and project to close enrollment in the ~~two key histology-based endpoints~~third quarter of ~~NASH resolution without worsening of fibrosis~~2022 and ~~the improvement of fibrosis ≥ 1 stage without worsening of NASH. We plan~~expect to ~~initiate the ENLIVEN~~report topline data from this trial in the ~~second quarter~~first half of ~~2021.~~

2023. Based on learnings from our recent cohort, developments in the field, and feedback from our steering committee, we have implemented steps to optimize the ENLIVEN trial. In 2021, we completed a pharmacokinetic study of pegozafermin in NASH patients with compensated cirrhosis (fibrosis stage F4) demonstrating that pegozafermin 30 mg has similar single-dose pharmacokinetics and pharmacodynamics in F4 as it does in non-cirrhotic NASH. We are currently evaluating the potential opportunity for pegozafermin in these fibrosis stage F4 patients. SHTG is a condition identified by severely elevated levels of triglycerides ~~(greater than or equal to~~ (≥500 mg/dL), which is associated with an increased risk of NASH, cardiovascular events and acute pancreatitis. We initiated our Phase 2 trial (ENTRIGUE) in SHTG patients in the third quarter of 2020 and expect to report topline data in the second ~~half~~quarter of ~~2021.~~2022. We closed enrollment in this trial in February 2022 with 85 patients enrolled. Subject to receipt of positive data and regulatory clearance, we plan to initiate a Phase 3 trial in 2023.

We commenced operations in 2018 and have devoted substantially all of our resources to raising capital, acquiring our initial product candidate, identifying and developing ~~BIO89-100,~~pegozafermin, licensing certain related technology, conducting research and development activities (~~including~~ (including preclinical studies and clinical trials) and providing general and administrative support for these operations.~~Prior to our initial public offering (“IPO”), we had funded our operations primarily from the issuance and sale of capital stock. In November 2019, we completed our IPO pursuant to which we issued~~ ~~6,100,390~~ ~~shares of our common stock at a price of $16.00 per share. We received net proceeds of $87.7 million from the IPO.~~

In July 2020, we completed an underwritten public offering of 3,047,040 shares of our common stock at a public offering price of $27.50 per share. We received net proceeds of $78.2 million after deducting underwriters’ discounts and commissions of $5.0 million and offering costs of approximately $0.6 million.

In September 2020, we completed an underwritten public offering of 3,025,000 shares of our common stock, at a public offering price of $28.00 per share. We received net proceeds of $79.5 million after deducting underwriting discounts and commissions of $4.6 million and offering costs of approximately $0.6 million.

As of March 31, ~~2021,~~2022, our cash and cash equivalents and short-term available-for-sale securities totaled ~~$189.6~~$126.1 million. Based on our current operating plan, we believe that our cash and cash equivalents and short-term available-for-sale securities, together with the proceeds available under our term loan facility, will be sufficient to meet our anticipated cash requirements for a period of at least one year from the date this Quarterly Report on Form 10-Q is filed with the Securities and Exchange Commission (“SEC”).

We have incurred net losses since our inception. Our net losses for the three months ended March 31, 2022 and 2021 ~~and 2020~~ were ~~$14.8~~$25.6 million and ~~$10.5~~$14.8 million, respectively. As of March 31, ~~2021,~~2022, we had an accumulated deficit of ~~$137.9~~$238.8 million. We expect to continue to incur significant expenses and increasing operating losses as we advance ~~BIO89-100~~pegozafermin and any future product candidates through clinical trials, seek regulatory approval for ~~BIO89-100~~pegozafermin and any future product candidates, expand our clinical, regulatory, quality, manufacturing and commercialization capabilities, protect our intellectual property, prepare for and, if approved, proceed to

commercializationof ~~BIO89-100~~pegozafermin and any futureproductcandidates,expand our generaland administrativesupportfunctions, includinghiringadditionalpersonnel,and incuradditionalcostsassociatedwith operatingas a publiccompany. Our net lossesmay fluctuatesignificantlyfromquarter-to-quarterand year-to-year,depending on the timingof our clinicaltrialsand our expenditureson otherresearchand developmentactivities.

The ongoing COVID-19 pandemic has disrupted and may continue to disrupt our business and delay our ~~preclinical and clinical programs and timelines.~~development timeline. The extent to which the COVID-19 pandemic may impact our future operating results and financial condition is uncertain. We initiated our Phase ~~2 trial~~ ~~(ENTRIGUE)~~ in SHTG patients in the third quarter of 2020 as well as a new paired-biopsy open-label histology cohort as part of the Phase 1b/2a trial in the fourth quarter of 2020. The COVID-19 surge observed late in the fourth quarter of 2020 and in the first quarter of 2021 has adversely impacted enrollment in these studies. While the recent COVID-19 surge in Europe has also resulted in enrollment challenges in certain geographies, we are working closely with our CRO and remain optimistic that enrollment will pick up in the trial.

~~We plan to initiate a Phase~~ 2b trial ~~(ENLIVEN)~~ in NASH patients in the ~~second quarter~~middle of the 2021. The COVID-19 pandemic has impacted execution and enrollment of our trials. We do not yet know the full extent of potential delays that may affect our clinical trials, which could prevent or delay us from obtaining approval for ~~BIO89-100.~~pegozafermin. Given the surges in cases of COVID-19 experienced previously and uncertainty regarding other variants, we cannot predict how our ongoing trials may be impacted. For more information regarding risks related to the ongoing COVID-19 pandemic, please see the risk factor entitled “The ongoing COVID-19 pandemic has resulted and may in the future result in significant disruptions to our clinical trials or other business operations, which could have a material adverse effect on our business,” in Part II. Item 1A of this Quarterly Report on Form 10-Q. To the extent the ongoing COVID-19 pandemic adversely affects our business and financial results, it may also have the effect of heightening many of the other risks set forth under “Risk Factors” in this Quarterly Report on Form 10-Q.

Research and development expenses consist primarily of costs incurred for the development of our lead product candidate, ~~BIO89-100.~~pegozafermin. Our research and development expenses consist primarily of external costs related to preclinical and clinical development, including costs related to acquiring patents and intellectual property, expenses incurred under license agreements and agreements with contract research organizations and consultants, costs related to acquiring and manufacturing clinical trial materials, including under agreements with contract manufacturing organizations and other vendors, costs related to the preparation of regulatory submissions and expenses related to laboratory supplies and services, as well as personnel costs. Personnel costs consist of salaries, employee benefits and stock-based compensation for individuals involved in research and development efforts.

We expense all research and development expenses in the periods in which they are incurred. We accrue for costs incurred as ~~the~~ services are ~~being~~ provided by monitoring the status of specific activities and ~~the~~ invoices received from our external service providers. We adjust our accrued expenses as actual costs become known.

Payments associated with licensing agreements to acquire licenses to develop, use, manufacture and commercialize products that have not reached technological feasibility and do not have alternate commercial use are expensed as incurred. Where contingent milestone payments are due to third parties under research and development arrangements or license agreements, the milestone payment obligations are expensed when the milestone results are probable and estimable, which is generally upon achievement of milestones.

We expect our research and development expenses to increase ~~substantially~~ for the foreseeable future as we continue the development of ~~BIO89-100~~pegozafermin and continue to invest in research and development activities. The process of conducting the necessary clinical research to obtain regulatory approval is costly and time consuming, and the successful development of ~~BIO89-100~~pegozafermin and any future product candidates is highly uncertain. To the extent that ~~BIO89-100~~pegozafermin continues to advance into larger and later stage clinical trials, our expenses will increase substantially and may become more variable. The actual probability of success for ~~BIO89-100~~pegozafermin or any future product candidate may be affected by a variety of factors, including the safety and efficacy of our product candidates, investment in our clinical programs, manufacturing capability and competition with other products. As a result, we are unable to determine the timing of initiation, duration and completion costs of our research and development efforts or when and to what extent we will generate revenue from the commercialization and sale of ~~BIO89-100~~pegozafermin or any future product candidate.

Generaland administrativeexpensesconsistprimarilyof personnelcosts,expensesfor outside professionalservices,includinglegal,human resource,auditand accountingservices,consultingcostsand allocatedfacilitiescosts.Personneland relatedcostsconsist

of salaries,benefitsand stock-basedcompensation for personnelin executive,financeand otheradministrativefunctions.Facilitiescostsconsistof rentand maintenanceof facilities.We expectour generaland administrativeexpensesto increasefor the foreseeable futureas weincreasethe sizeof our administrativefunctionto supportthe growth of our businessand support our continuedresearchand developmentactivities.

Other ~~(expenses) income~~expenses,net primarily consistsofinterest ~~on available-for-sale securities and~~expense, amortization of deferred debt issuance ~~costs.~~costs and amortization of premium on available-for-sale securities offset by interest income on available-for-sale securities.

The followingtablesummarizesour resultsof operationsfor the periodspresented(in thousands):

	Three Months Ended
	March 31,
	2022			2021			Change
Operating expenses:
Research and development	$	19,849		$	10,131		$	9,718
General and administrative		5,259			4,608			651
Total operating expenses		25,108			14,739			10,369
Loss from operations		(25,108	)		(14,739	)		(10,369	)
Other expenses, net		(456	)		(43	)		(413	)
Net loss before tax	$	(25,564	)	$	(14,782	)	$	(10,782	)

The followingtablesummarizesthe period-over-periodchanges in researchand developmentexpenses for the periods presented (in thousands):

Three Months Ended

March 31,

2021

2020

Change

Operating expenses:

Research and development

$
10,131

$
7,778

$
2,353

General and administrative

4,608

2,924

1,684

Total operating expenses

14,739

10,702

4,037

Loss from operations

(14,739
)

(10,702
)

(4,037
)
Other (expenses) income, net

(43
)

157

(200
)
Income tax benefit

—

1

(1
)
Net loss

$
(14,782
)

$
(10,544
)

$
(4,238
)

	Three Months Ended
	March 31,
	2022		2021		Change
Clinical development	$	11,185	$	3,681	$	7,504
Contract manufacturing		4,314		3,389		925
Personnel-related expenses		3,945		2,584		1,361
Preclinical costs		—		135		(135	)
Other expenses		405		342		63
Total research and development expenses	$	19,849	$	10,131	$	9,718

~~The following table summarizes the period-over-period changes in research~~ and developmentexpenses ~~for the periods~~ ~~presented~~ ~~(in thousands):~~

Three Months Ended

March 31,

2021

2020

Change

Clinical development

$
3,681

$
4,348

$
(667
)
Contract manufacturing

3,389

1,191

2,198

Personnel-related expenses

2,584

1,403

1,181

Preclinical costs

135

656

(521
)
Other expenses

342

180

162

Total research and development expenses

$
10,131

$
7,778

$
2,353

~~Research and development expenses~~ increased by ~~$2.4~~$9.7 million,or ~~30%~~96%, to ~~$10.1~~$19.8 million for the three monthsended March 31, ~~2021~~2022 from ~~$7.8~~$10.1 million for the three months ended March 31, ~~2020.~~2021. The changewas primarilydue to an increase of ~~$2.2~~$7.5 million in ~~contract manufacturing~~clinical development costs ~~as a result of the manufacture of additional supplies for~~related to our ongoing clinical trials, ~~including our clinical trials initiated in the second half of 2020 and~~ an increase of ~~$1.2~~$1.4 million in personnel-related costs, including stock-based compensation due to higher ~~headcount. The increases were partially offset by~~headcount, and an increase of $0.9 million in contract manufacturing costs, mainly as a ~~decrease~~result of the manufacture of supplies and the scaling up of manufacturing for our ongoing clinical trials.

Generaland administrativeexpensesincreasedby $0.7 million, ~~in clinical development costs and a decrease of $0.5 million in preclinical costs. The timing of such costs is dependent upon the status and stage of our clinical trials.~~

~~General and administrative expenses increased by $1.7 million,~~ or ~~58%~~14%, to ~~$4.6~~$5.3 millionfor the three monthsended March 31, 2022 from$4.6 millionfor the three months ended March 31, ~~2021 from $2.9~~2021. The changewas due to an increase of $1.0 millionin personnel-relatedcosts,includingstock-based compensation,drivenby higher headcount, partially offset by a decrease of $0.3 million in professionalservices related to legal and consulting services.

Other expenses,net increasedby $0.4 million to $0.5 million for the three months ended March 31, 2020. The change was primarily due to an increase of $1.1 million in personnel-related costs, including stock-based compensation, driven by higher headcount, an increase of $0.5 million in insurance related costs and an increase of $0.1 million in professional services including legal and accounting consulting service fees.

~~Other (expenses) income, net changed by $0.2 million~~ ~~to net expense of~~ 2022from$43,000 for the three months ended March 31, 2021, ~~from~~ ~~net income of~~ ~~$0.2 million~~ ~~for the three months ended~~ ~~March 31, 2020~~. ~~The change was~~ primarily due to interest expense, including the accretion of the final payment fee and amortization of ~~deferred~~ debt issuance costs, ~~in 2021 offset by interest income.~~related to our term loan facility.

To date, we have incurred significant net losses and negative cash flows from operations. Asof March 31, ~~2021,~~2022, wehad availablecash and cash equivalents and short-term available-for-sale securities of ~~$189.6~~$126.1 millionand an accumulateddeficitof ~~$137.9 million. Prior to our IPO, we funded our operations from the issuance and sale of capital stock.~~ ~~In connection with our IPO, we issued and sold an aggregate of 6,100,390 shares of common stock at a price of $16.00 per share. We received proceeds of $87.7~~$238.8 million ~~net of underwriting discounts and commissions and estimated offering costs.~~.

In ~~April 2020,~~March 2021, we entered into a ~~secured term loan facility~~sales agreement (the “Sales Agreement”) with ~~an aggregate committed principal amount of~~SVB Leerink LLC and Cantor Fitzgerald & Co. (the “Sales Agents”) pursuant to which we may offer and sell up to ~~$15.0 million.~~ ~~In March 2021 and April 2021,~~$75.0 million of shares of our common stock, from time to time, in “at-the-market” offerings (the “ATM Facility”). The Sales Agents are entitled to compensation at a commission equal to 3.0% of the Company entered into amendments to the Loan Agreement to extend the draw period for the Term A Loan Facility and the Term B Loan Facility from March 31, 2021 to May 31, 2021. As of March 31, 2021, we have not drawn any amount

Sales Agreement. In ~~July 2020,~~ October and November 2021,we ~~completed an underwritten public~~received aggregate proceeds of $3.3 million, net of commissions and offering expenses from sales of ~~3,047,040~~186,546 shares of our common stock at a ~~public offering~~weighted-average price of ~~$27.50~~$17.97 per ~~share. Upon completion~~share pursuant to the ATM Facility. For the three months ended March 31, 2022, there were no sales pursuant to the ATM Facility.

In May 2021, we amended our secured term loan facility (“2021 Loan Agreement”) to increase the aggregate committed principal amount up to $25.0 million. As of March 31, 2022, we had drawn $20.0 million under the ~~offering, we received proceeds~~term loan facility and $5.0 million remains available to be drawn on or before September 30, 2022, upon achievement of ~~$78.2 million, net of underwriting discounts and commissions and offering expenses.~~

In September 2020, we completed an underwritten public offering of 3,025,000 shares of our common stock, at a public offering price of $28.00 per share. Upon completion of the offering, we received proceeds of $79.5 million, net of underwriting discounts and commissions and offering expenses.certain milestones.

Our primaryuse of cash is to fund operatingexpenses,which consistprimarilyof researchand developmentexpendituresrelatedto our lead productcandidate, ~~BIO89-100.~~pegozafermin. We plan to increaseour research and developmentexpenses ~~substantially~~ for the foreseeablefutureas wecontinuethe clinicaldevelopmentof our currentand futureproductcandidates.At thistime,due to the inherentlyunpredictablenatureof clinical development,wecannot reasonablyestimatethe costswewill incurand the timelinesthatwill be requiredto completedevelopment,obtainmarketingapproval,and commercializeour currentproductcandidateor any futureproductcandidates.For the samereasons,weare also unable to predictwhen,if ever, wewill generate revenuefromproductsalesor our currentor any futurelicenseagreementswhich wemay enterinto or whether, or when,if ever, wemay achieveprofitability.Clinicaland preclinicaldevelopmenttimelines,the probabilityof success,and developmentcostscan differmateriallyfromexpectations.In addition,wecannot forecastthe timingand amountsof milestone,royaltyand otherrevenuefromlicensingactivities,which futureproduct candidatesmay be subjectto futurecollaborations,whensuch arrangementswill be secured,if at all,and to what degreesuch arrangementswould affectour developmentplans and capitalrequirements.

Based on our researchand developmentplans, weexpectthatour existingcash and cash equivalents and short-term available-for-sale securities as of March 31, 2022, together with the proceeds available ~~under~~from our term loan facility and our ATM Facility,will be sufficientto fund our operations for a period of at least one year from the date this Quarterly Report on Form 10-Q is filed with the SEC.However, our operatingplans and otherdemandson our cash resourcesmay change as a resultof many factors,and wemay seek additionalfunds sooner than planned. There can be no assurancethatwewill be successfulin acquiringadditionalfunding at levelssufficientto fund our operationsor on termsfavorableto us.

Our futurefunding requirementswill depend on many factors,includingthe following:

We expect to continue to generate substantial operating losses for the foreseeable future as we expand our research and development activities. We will continue to fund our operations primarily through utilization of our current financial resources and through additional raises of capital to advance our current product candidate through clinical development, to develop, acquire or in-license other potential product candidates and to fund operations for the foreseeable ~~future~~.future. However, there is no assurance that such funding will be available to us or that it will be obtained on terms favorable to us or will provide us with sufficient funds to meet our objectives. Any failure to raise capital as and when needed could have a negative impact on our financial condition and on our ability to pursue our business plans and strategies.

To the extent that we raise additional capital through partnerships or licensing arrangements with third parties, we may have to relinquish valuable rights to our product candidates, future revenue streams or research programs or to grant licenses on terms that

may not be favorable to us. If we raise additional capital through public or private equity offerings, the ownership interest of our then-existing stockholders will be diluted, and the terms of these securities may include liquidation or other preferences that adversely affect our stockholders’ rights. If we raise additional capital through debt financing, we may be subject to covenants limiting or restricting our ability to take specific actions, such as incurring additional debt, making capital expenditures or declaring dividends. If we are unable to obtain adequate financing when needed, we may have to delay, reduce the scope of or suspend one or more of our clinical trials or preclinical studies, research and development programs or commercialization efforts or grant rights to develop and market our product candidates even if we would otherwise prefer to develop and market such product candidates ourselves.

The followingtablesummarizesour cash flows for the periods presented ~~(in~~(in thousands):

Three Months Ended

March 31,

2021

2020

Net cash used in operating activities

$
(14,982
)

$
(7,752
)
Net cash used in investing activities

(15,410
)

(61
)
Net cash provided by financing activities

216

9

Net decrease in cash and cash equivalents,
and restricted cash

$
(30,176
)

$
(7,804
)

	Three Months Ended
	March 31,
	2022			2021
Net cash used in (provided by)
Operating activities	$	(24,344	)	$	(14,982	)
Investing activities		26,772			(15,410	)
Financing activities		29			216
Net change in cash and cash equivalents, and restricted cash	$	2,457		$	(30,176	)

During the three monthsended March 31, 2022, net cash used in operatingactivitieswas $24.3 million, which consistedof a net loss of $25.6 million and a net change of $1.6 millionin our net operatingassetsand liabilities, partially offset by non-cash charges of $2.8 million. The non-cashchargesare primarilycomprised of $2.5 millionin stock-based compensation, $0.1 million in accretion of the final payment fee related to our term loan facility, $0.1 million in amortization of premium on available-for-sale securities and $0.1 million in amortization of debt issuance costs.The change in our operatingassetsand liabilitieswas primarilydue to a $3.6 milliondecreasein accounts payable and accruedexpenses due to the timing of our payables, offset in part by a $2.0 million decrease in prepaid and other current assets due to the timing of payments.

During the three months ended March 31, 2021, net cash used in operating activities was $15.0 million, which consisted of a net loss of $14.8 million and a net change of $2.3 million in our net operating assets and liabilities, partially offset by non-cash charges of $2.1 million. The non-cash charges are primarily comprised of $1.8 million in stock-based compensation, $0.2 million in amortization of premium on available-for-sale securities and $0.1 million in amortization of debt issuance costs. The change in our operating assets and liabilities was primarily due to a $2.7 million increase in prepaid and other current assets due to the timing of payments, offset in part by a $0.3 million increase in accounts payable and accrued expenses due to increased activities.

During the three months ended March 31, 2020, net cash used in operating activities was $7.8 million, which consisted of a net loss of $10.5 million, partially offset by non-cash charges of $0.5 million and a net change of $2.3 million in our net operating assets and liabilities. The non-cash charges are primarily comprised of $0.5 million in stock-based compensation. The change in our operating assets and liabilities was primarily due to a $2.2 million increase in accounts payable and accrued expenses as we grew our operations and a $0.1 million decrease in other current assets due to the timing of payments.

During the three monthsended March 31, 2022, net cash provided by investing activities was $26.8 million, which primarily consisted of $36.2 million in proceeds from maturities of available-for-sale securities, offset in part by $9.4 million in purchases of available-for-sale securities.

During the three monthsended March 31, 2021, net cash used in investing activities was $15.4 million, which consisted of $45.3 million in purchases of available-for-sale securities, offset in part by $29.9 million in proceeds from maturities of available-for-sale securities.

~~During the three months ended March 31, 2020, net cash used in investing activitiesconsistedof purchasesof fixedassets.~~

During the three monthsended March 31, ~~2021~~2022 and ~~2020,~~2021, net cash provided by financingactivities consisted of proceeds from the issuance of common stock upon exercise of stock options.

Our 2021 Loan Agreement provides for a total term loan facility of $25.0 million. As of March 31, 2022, we had drawn $20.0 million under the term loan facility and are required to make interest-only payments until October 1, 2022 followed by consecutive monthly payments of principal and interest starting on October 1, 2022 and continuing through September 1, 2024, the maturity date of the term loan. The interest-only period may be extended to April 1, 2023, if on or before September 20, 2022, we receive net

cash proceeds of at least $75.0 million from the sale of our equity securities. Our term loan bears interest at the greater of (i) 4.25% and (ii) the sum of (a) the Prime Rate as reported in The Wall Street Journal plus (b) 1.00%. The interest rate on the term loan was 4.25% at inception and 4.50% as of March 31, 2022. In addition, a final payment fee of 5% of the principal amount of the loan is due when the term loan becomes due or upon prepayment of the term loan. If we elect to prepay the loan, there is also a prepayment fee of between 1% and 3% of the principal amount of the term loan depending on the timing of prepayment.

~~We are a smaller reporting company, as defined by Rule 12b-2 under the Securities and Exchange Act of 1934 and in Item 10(f)(1) of Regulation S-K, and are not required~~See Note 5 to ~~provide the information under this item.~~

~~We have not entered into any off-balance sheet arrangements, as defined in the rules and regulations of the SEC, and do not have any holdings in variable interest entities.~~

our condensed consolidated financial statements for additional disclosures. There have been no ~~significant~~other material changes ~~in our critical accounting policies and estimates as compared to~~from the ~~critical accounting policies and estimates~~contractual obligations disclosed in our Annual Report on Form 10-K for the year ended December 31, ~~2020.~~2021.

There have been no significant changes in our critical accounting estimates as compared to the critical accounting estimates disclosed in our Annual Report on Form 10-K for the year ended December 31, 2021.

See Note 2 to our condensed consolidated financial statements for more ~~information.~~information.

We are an emerginggrowth company,as definedin the JOBSAct. Under the JOBSAct, emerging growth companiescan delay adoptingnewor revisedaccountingstandardsissuedsubsequentto the enactmentof the JOBSAct untilsuch timeas those standardsapply to privatecompanies.

We have electedto use thisextendedtransitionperiodto enableus to complywith newor revised accountingstandardsthathave differenteffectivedatesfor publicand privatecompaniesuntilthe earlierof the date we(i)are no longeran emerginggrowth company or (ii)affirmativelyand irrevocablyopt out of the extendedtransitionperiodprovidedin the JOBSAct. Asa result,our consolidatedfinancialstatementsand our interim condensed consolidated financialstatementsmay not be comparableto companiesthatcomplywith new or revisedaccountingpronouncements.

We are a smaller reporting company, as defined by Rule 12b-2 under the Securities and Exchange Act of 1934 and in Item 10(f)(1) of Regulation S-K, and are not required to provide the information under this item.

As of March 31, ~~2021,~~2022, our management, with the participation and supervision of our principal executive officer and our principal financial officer, evaluated our disclosure controls and procedures (as defined in Rules 13a-15(e) and 15d-15(e) under the Exchange Act). 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 it files or submits under the Exchange Act is recorded, processed, summarized and reported, within the time periods specified in the SEC’s rules and forms. Disclosure controls and 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 the Company’s management, including its principal executive and principal financial officers, as appropriate to allow timely decisions regarding required disclosure. 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. Based on this evaluation, our principal executive officer and our principal financial officer concluded that our disclosure controls and procedures were effective as of March 31, ~~2021~~2022 to provide reasonable assurance that information we are required to disclose in reports that we file or submit under the Exchange Act is recorded, processed, summarized, and reported within the time periods specified in SEC rules and forms, and that such information is accumulated and communicated to our management, including our principal executive officer and our principal financial officer, as appropriate, to allow timely decisions regarding required disclosure.

There were no changes 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 quarter ended March 31, ~~2021~~2022 that has materially affected, or is reasonably likely to materially affect, our internal control over financial reporting.

We are currently not a party to any material legal proceedings. From time to time, we may become involved in legal proceedings arising in the ordinary course of our business. Regardless of outcome, litigation can have an adverse impact on us due to defense and settlement costs, diversion of management resources, negative publicity, reputational harm and other factors, and there can be no assurances that favorable outcomes will be obtained.

An investment in our common stock involves a high degree of risk. You should carefully consider the risks and uncertainties described below before deciding whether to make an investment decision with respect to shares of our common stock. You should also refer to the other information contained in this Quarterly Report on Form 10-Q, including “Management’s Discussion and Analysis of Financial Condition and Results of Operations” and our unaudited condensed consolidated financial statements and related notes. Our business, financial condition, results of operations and prospects could be materially and adversely affected by any of these risks or uncertainties. In any such case, the trading price of our common stock could decline, and you could lose all or part of your investment. We caution you that the risks, uncertainties and other factors referred to below and elsewhere in this Quarterly Report on Form 10-Q may not contain all of the risks, uncertainties and other factors that may affect our future results and operations. Moreover, new risks will emerge from time to time. It is not possible for our management to predict all ~~risks.~~risks.

Investing in our common stock involves significant risks. You should carefully consider the risks described below before making a decision to invest in our common stock. If we are unable to successfully address these risks and challenges, our business, financial condition, results of operations, or prospects could be materially adversely affected. In such case, the trading price of our common stock would likely decline, and you may lose all or part of your investment. Below is a summary of some of the risks we face.

Wewill requiresubstantialadditionalcapitalto finance our operations, whichmay not be availableto us onacceptableterms,or at all. Asa result,wemay not completethe developmentandcommercializationof pegozaferminor developnewproduct candidates.

As a clinical-stage biopharmaceutical company, our operations have consumed significant amounts of cash since our inception. We expect our research and development expenses to increase in connection with our ongoing activities, particularly as we conduct clinical trials of and seek regulatory approvals for pegozafermin. We believe that our existing cash and cash equivalents and short-term available-for-sale securities, together with the proceeds available from our line of credit pursuant to our Loan and Security Agreement (as amended, the “2021 Loan Agreement”) with Silicon Valley Bank (“SVB”) will fund our projected operating requirements for a period of at least one year from the date of this Annual Report on Form 10-K is filed with the SEC.

We will require additional capital to discover, develop, obtain regulatory approval for and commercialize pegozafermin and any future product candidates. Our ability to commence new clinical trials for pegozafermin is subject to our ability to raise additional capital. We do not have any committed external source of funds other than the unused portion of the line of credit available to us pursuant to the 2021 Loan Agreement and as a result of any sales that we may make pursuant to the sales agreement for our “at-the-market” offering facility. We expect to finance future cash needs through public or private equity or debt offerings or product collaborations. Additional capital may not be available in sufficient amounts or on reasonable terms, if at all. The current market environment for small biotechnology companies, like 89bio, and broader macroeconomic factors may preclude us from successfully raising additional capital.

If we do not raise additional capital, we may not be able to expand our operations or otherwise capitalize on our business opportunities, our business and financial condition will be negatively impacted and we may need to: significantly delay, scale back or discontinue research and discovery efforts and the development or commercialization of any product candidates or cease operations altogether; seek strategic alliances for research and development programs when we otherwise would not, or at an earlier stage than we would otherwise desire or on terms less favorable than might otherwise be available; or relinquish, or license on unfavorable terms, our rights to technologies or any product candidates that we otherwise would seek to develop or commercialize ourselves.

In addition, if pegozafermin receives approval and is commercialized, we will be required to make milestone and royalty payments to Teva, from whom we acquired certain patents and intellectual property relating to pegozafermin, and from whom we licensed patents and know-how related to glycoPEGylation technology that is used in the manufacture of pegozafermin. For additional information regarding this license agreement, please see Note 5 of our accompanying unaudited condensed consolidated financial statements.

We are a clinical-stage biopharmaceuticalcompany with a limitedoperatinghistoryandnoproducts approvedfor commercialsale. We have incurred net lossessince our inception,weexpectto incur significantand increasingoperatinglossesandwemay never be profitable.Ourstock is a highly speculativeinvestment.

We are a clinical-stage biopharmaceutical company with a limited operating history that may make it difficult to evaluate the success of our business to date and to assess our future viability. We commenced operations in 2018, and to date, our operations have been focused on organizing and staffing our company, raising capital, acquiring our initial product candidate, ~~BIO89-100~~pegozafermin and licensing certain related technology, conducting research and development activities, including preclinical studies and clinical trials, and providing general and administrative support for these operations. Investment in biopharmaceutical product development is highly speculative because it entails substantial upfront capital expenditures and significant risk that any potential product candidate will fail to demonstrate adequate effect and/or an acceptable safety profile, gain regulatory approval and become commercially viable. We have no products approved for commercial sale, we have not generated any revenue from product sales to date and we continue to incur significant research and development and other expenses related to our ongoing operations. We have limited experience as a company conducting clinical trials and no experience as a company commercializing any products.

~~BIO89-100~~Pegozafermin is in development and, to date, we have not generated any revenue from the licensing or commercialization of ~~BIO89-100.~~pegozafermin. We will not be able to generate product revenue unless and until ~~BIO89-100~~pegozafermin or any future product candidate, alone or with future partners, successfully completes clinical trials, receives regulatory approval and is successfully commercialized. As ~~BIO89-100~~pegozafermin is in development, we do not expect to receive revenue from it for a number of years, if ever. Although we may seek to obtain revenue from collaboration or licensing agreements with third parties, we currently have no such agreements that could provide us with material, ongoing future revenue and we may never enter into any such agreements.

We are not profitable and have incurred net losses since our inception. Consequently, predictions about our future success or viability may not be as accurate as they would be if we had a longer operating history or a history of successfully developing and commercializing pharmaceutical products. We have spent, and expect to continue to spend, significant resources to fund research and development of, and seek regulatory approvals for, ~~BIO89-100~~pegozafermin and any future product candidates. We expect to incur substantial and increasing operating losses over the next several years as our research, development clinical trial and manufacturing activities increase. In addition, because of the numerous risks and uncertainties associated with pharmaceutical product development, including that our product candidates may not advance through development or achieve the endpoints of applicable clinical trials, we are unable

to predict the timing or amount of increased expenses, or if or when we will achieve or maintain profitability. The size of our future net losses will depend, in part, on the rate of future growth of our expenses and our ability to generate revenue. The net losses we incur may fluctuate significantly from quarter-to-quarter such that a period-to-periodcomparisonof our resultsof operationsmay not be a good indicationof our future performance.Even if weeventuallygenerateproductrevenue,wemay never be profitableand, if wedo achieve profitability,wemay not be able to sustainor increaseprofitabilityon a quarterlyor annual basis.

The ongoing COVID-19 pandemic has resulted and may in the future result in significant disruptions to our clinical trials or other business operations, which could have a material adverse effect on our business.

Our business and its operations, including but not limited to our research and development activities, could be adversely affected by health epidemics in regions where we have business operations, and such health epidemics could cause significant disruption in the operations of third parties upon whom we rely. In response to ~~public health directives and orders related to~~ COVID-19, ~~and based on guidance from public health officials,~~ we have implemented ~~and continue to implement work-from-home policies for our employees on an office-by-office basis.~~hybrid work policy. The effects of ~~executive and similar government orders, shelter-in-place orders and our work-from-home policies~~which may negatively impact our growth, including our ability to recruit and onboard new employees, and productivity, disrupt our business and delay our preclinical and clinical programs and timelines, 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. These and similar, and perhaps more severe, disruptions in our operations could negatively impact our business, operating results and financial condition.productivity.

Our clinical trials have been and may continue to be affected by the COVID-19 pandemic. For example, while we initiated the Phase 2 trial (ENTRIGUE) of BIO89-100 for the treatment of SHTG and a paired-biopsy histology cohort as part of the Phase 1b/2a trial of BIO89-100 in NASH in 2020, our successful completion of these trials will depend on the external environment with respect to COVID-19 remaining conducive to executing the trial safely and effectively. The COVID-19 ~~surge observed late~~pandemic has impacted execution and enrollment of our trials. Given the surges in ~~the fourth quarter~~cases of ~~2020~~COVID-19 experienced previously and ~~in the first quarter of 2021 has adversely impacted enrollment in these studies. While the recent COVID-19 surge in Europe has also resulted in enrollment challenges in certain geographies,~~uncertainty regarding other variants, we ~~are working closely with~~cannot predict how our ~~CRO and remain optimistic that enrollment will pick up in the trial.~~ ~~Similarly, while we expect to initiate the Phase 2b trial (ENLIVEN) of BIO89-100 in NASH patients in the second quarter of 2021, we~~ongoing or future trials may be ~~delayed in the initiation of such trial due to COVID-19 or related government restrictions.~~ impacted.

In addition, quarantines, shelter-in-place, executive 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, have~~has impacted and may continue to impact personnel at third-party manufacturing facilities in the United States, Europe and other countries, or the availability or cost of materials we use or require to conduct our business, including product development, which would disrupt our supply chain. Furthermore, some of our manufacturers and suppliers are in Europe and may be impacted by port closures and other restrictions resulting from the COVID-19 pandemic, which may disrupt our supply chain or limit our ability to obtain sufficient materials for our drug products. In particular, BTPH, our sole source supplier for ~~BIO89-100,~~pegozafermin, has missed certain project deadlines for our manufacturing scale-up due to quarantine orders and has forecasted other delays due to COVID-19-related impacts on their suppliers. Furthermore, we have experienced and may continue to experience delays due to widespread supply chain issues relating to the COVID-19 pandemic, as well as historically the designation of certain supplies for vaccine production, which may limit our ability to obtain sufficient materials for our drug products. However, we have not experienced and do not expect to experience any delays to the overall timeline for the delivery of clinical supplies.

If COVID-19 continues to spread in the United States and elsewhere, we may experience additional disruptions that could severely impact our business, preclinical studies and clinical trials, including: delays in receiving authorization from local regulatory authorities to initiate our planned clinical trials; delays or difficulties in enrolling patients in our clinical trials; delays or difficulties in clinical site initiation, including difficulties in recruiting clinical site investigators and clinical site staff; delays in clinical sites receiving the supplies and materials needed to conduct our clinical trials; changes in local regulations as part of a response to the COVID-19 pandemic which may require us to change the ways in which our clinical trials are conducted and result in unexpected costs, or discontinuing our clinical trials altogether; a diversion of healthcare resources away from the conduct of clinical trials, including the diversion of hospitals serving as our clinical trial sites and hospital staff supporting the conduct of our clinical trials; interruption of key clinical trial activities, such as clinical trial site monitoring and data entry and verification, due to limitations on travel imposed or recommended by federal or state governments, employers and others, or interruption of clinical trial subject visits and study procedures, the occurrence of which could affect the completeness and integrity of clinical trial data and, as a result,

determine the outcomes of the trial; the risk that participants enrolled in our clinical trials will acquire COVID-19 while the clinical trial is ongoing, which could impact the results of the clinical trial, including by increasing the number of observed adverse events; the risk that participants enrolled in our clinical trials will not be able to travel to our clinical trial sites as a result of quarantines or other restrictions resulting from COVID-19 or comply with clinical trial protocols if quarantines impede patient movement or interrupt healthcare services; interruptions or delays in preclinical studies due to restricted or limited operations at our research and development laboratory facilities; limitations in employee resources that would otherwise be focused on the conduct of our clinical trials; the refusal of the FDA to accept data from clinical trials in affected geographies; and interruption or delays to our clinical activities.

The COVID-19 pandemic continues to ~~evolve rapidly.~~evolve. The ultimate impact of the COVID-19 pandemic or a similar public health emergency is highly uncertain and subject to change. We do not yet know the full extent of potential delays or impacts on our business, our clinical trials, healthcare systems, or the global economy as a whole. However, any one or a combination of these events could have an adverse effect on the operation of and results from our clinical trials and on our other business operations, including preventing or delaying approval for ~~BIO89-100.~~pegozafermin.

Ourbusiness depends onthe success of ~~BIO89-100,~~ pegozafermin,our only product candidateunder clinicaldevelopment, whichhas not completeda pivotaltrial.If weare unable to obtain regulatoryapproval for andsuccessfullycommercialize ~~BIO89-100~~ pegozaferminor other future product candidates, or weexperiencesignificantdelaysin doing so, our business will be materiallyharmed.

To date, the primary focus of our product development has been ~~BIO89-100~~pegozafermin for the treatment of patients with NASH. Currently, ~~BIO89-100~~pegozafermin is our only product candidate under clinical development. This may make an investment in our company riskier than similar companies that have multiple product candidates in active development and that therefore may be able to better sustain a failure of a lead candidate. Successful continued development and ultimate regulatory approval of ~~BIO89-100~~pegozafermin for the treatment of NASH or other indications, including SHTG, is critical to the future success of our business. We have invested, and will continue to invest, a significant portion of our time and financial resources in the clinical development of ~~BIO89-100.~~pegozafermin. If we cannot successfully develop, obtain regulatory approval for and commercialize ~~BIO89-100,~~pegozafermin, we may not be able to continue our operations. The future regulatory and commercial success of ~~BIO89-100~~pegozafermin is subject to a number of risks, including that if approved for NASH or SHTG, ~~BIO89-100~~pegozafermin will likely compete with products that may reach approval for the treatment of NASH prior to ~~BIO89-100,~~pegozafermin, products that are currently approved for the treatment of SHTG and the off-label use of currently marketed products for NASH and SHTG.

Clinicaldrug developmentinvolvesa lengthy andexpensiveprocesswith uncertain timelinesanduncertain outcomes,andthe resultsof prior preclinicalor clinicaltrialsare not necessarilypredictiveof our future results.

~~BIO89-100~~Pegozafermin and any future product candidates will be subject to rigorous and extensive clinical trials and extensive regulatory approval processes implemented by the FDA and comparable foreign regulatory authorities before obtaining marketing approval from these regulatory authorities. The drug development and approval process is lengthy and expensive, and approval is never certain. Investigational new drugs, such as ~~BIO89-100,~~pegozafermin, may not prove to be safe and effective in clinical trials. We have no direct experience as a company in conducting ~~later stage clinical~~pivotal trials required to obtain regulatory approval. We may be unable to conduct clinical trials at preferred sites, enlist clinical investigators, enroll sufficient numbers of participants or begin or successfully complete clinical trials in a timely fashion, if at all. In addition, the design of a clinical trial can determine whether its results will support approval of a product, and flaws in the design of a clinical trial may not become apparent until the clinical trial is well advanced. We may be unable to design and execute a clinical trial to support regulatory approval. Even if a current clinical trial is successful, it may be insufficient to demonstrate that ~~BIO89-100~~pegozafermin is safe or effective for registration purposes.

There is a high failure rate for drugs and biologic products proceeding through clinical trials. Failure can occur at any time during the clinical trial process. The results of preclinical studies and early clinical trials of ~~BIO89-100~~pegozafermin or any future product candidate may not be predictive of the results of later-stage clinical studies or trials and the results of studies or trials in one set of patients or line of treatment may not be predictive of those obtained in another. In fact, many companies in the pharmaceutical and biotechnology industries have suffered significant setbacks in ~~late stage~~late-stage clinical trials even after achieving promising results in preclinical studies and earlier stage clinical trials. In addition, data obtained from preclinical and clinical activities is subject to varying interpretations, which may delay, limit or prevent regulatory approval. It is impossible to predict when or if ~~BIO89-100~~pegozafermin or any future product candidate will prove effective or safe in humans or will receive regulatory approval. Owing in part to the complexity of biological pathways, ~~BIO89-100~~pegozafermin or any future product candidate may not demonstrate in patients the biochemical and pharmacological properties we anticipate based on laboratory studies or earlier stage clinical trials, and they may interact with human biological systems or other drugs in unforeseen, ineffective or harmful ways. The number of patients exposed to product candidates and the average exposure time in the clinical development programs may be inadequate to detect rare adverse events or findings that may only be detected once a product candidate is administered to more patients and for greater periods of time. To date, our Phase 1a and Phase 1b/2a clinical trials have involved small patient populations and, because of the small sample size in such trials, the results of these clinical trials may be subject to substantial variability, including the inherent variability associated with biopsies in NASH patients, and may not be indicative of either future interim results or final results in future trials of patients with liver or cardio-metabolic diseases. If we are unable to successfully demonstrate the safety and efficacy of ~~BIO89-100~~pegozafermin or other future product candidates and receive the necessary regulatory approvals, our business will be materially harmed.

If weexperiencedelaysin clinicaltesting,our commercialprospectswill be adverselyaffected,our costsmay increaseandour business may be harmed.

We cannot guarantee that we will be able to initiate and complete clinical trials and successfully accomplish all required regulatory activities or other activities necessary to gain approval and commercialize ~~BIO89-100~~pegozafermin or any future product candidates. We

currentlyhave two activeinvestigational new drug (“IND”) applicationswith the FDAin the United Statesfor ~~BIO89-100.~~pegozafermin. In the future,wemay filean additionalINDwith anotherdivisionfor any futureindications or future product candidates.If any such futureINDis not approved by the FDA,our clinicaldevelopmenttimelinemay be negativelyimpactedand any futureclinical programsmay be delayedor terminated. Asa result,wemay be unable to obtainregulatoryapprovalsor successfullycommercializeour products.We do not knowwhether any otherclinicaltrialswill begin as planned, will need to be restructuredor will be completedon schedule,or at all.Our productdevelopmentcostswill increaseif weexperiencedelaysin clinicaltesting.Significantclinicaltrialdelaysalso could shortenany periods during which wemay have the exclusiverightto commercialize~~BIO89-100~~ pegozafermin and any futureproductcandidatesor allow our competitorsto bring productsto marketbeforewedo, which would impairour abilityto successfully commercialize~~BIO89-100~~ pegozafermin or any futureproductcandidatesand may harmour business,resultsof operationsand prospects.Our or our futurecollaborators’inabilityto timelycompleteclinicaldevelopmentcould resultin additionalcoststo us as well as impairour abilityto generateproductrevenue,continuedevelopment, commercialize~~BIO89-100~~ pegozafermin and any futureproductcandidates,reachsalesmilestonepaymentsand receive royaltieson productsales.In addition,if wemake changes to a productcandidate including, for example, a new formulation,wemay need to conduct additionalnonclinicalstudiesor clinicaltrialsto bridgeor demonstratethe comparabilityof our modifiedproduct candidateto earlierversions,which could delay our clinicaldevelopmentplan or marketingapprovalfor our currentproductcandidateand any futureproductcandidates.

If weencounter difficultiesin enrollingpatientsin our clinicaltrials,our clinicaldevelopmentactivitiescould be delayedor otherwiseadverselyaffected.

The timely completion of clinical trials largely depends on patient enrollment. We may encounter delays in enrolling, or be unable to enroll, a sufficient number of patients to complete any of our future clinical trials, and even once enrolled, we may be unable to retain a sufficient number of patients to complete any of our trials. Furthermore, ~~as a result of the~~there are inherent difficulties in diagnosing NASH, which can currently only be definitively diagnosed through a liver biopsy, and identifying SHTG patients. Specifically, identifying patients most likely to meet NASH enrollment criteria on biopsy is an on-going challenge, with existing clinical indicators lacking both sensitivity and specificity. As a result, NASH trials often suffer from high levels of screen failure following central review of the baseline liver biopsy, which can lead to lower enrollment. As a result of such difficulties and the significant competition for recruiting NASH and SHTG patients in clinical trials, we or our future collaborators may be unable to enroll the patients we need to complete clinical trials on a timely basis, or at all. In addition, our competitors, some of whom have significantly greater resources than we do, are conducting clinical trials for the same indications and seek to enroll patients in their studies that may otherwise be eligible for our clinical studies or trials. Since the number of qualified clinical investigators is limited, we expect to conduct some of our clinical trials at the same clinical trial sites that some of our competitors use, which could further reduce the number of patients who are available for our clinical trials in these sites. Our inability to enroll a sufficient number of patients for our clinical trials would result in significant delays or may require us to abandon one or more clinical trials altogether. Even if we are able to enroll a sufficient number of patients in our clinical studies or trials, delays in patient enrollment may result in increased costs or may affect the timing or outcome of our clinical trials, which could prevent completion of these trials and adversely affect our ability to advance the development of ~~BIO89-100~~pegozafermin and any future product candidates.

~~BIO89-100~~We have relied on, and expect to continue to rely on, third-party manufacturers and vendors to produce and release pegozafermin or any future product candidates. Any failure by a third-party to produce and release acceptable product candidates for us pursuant to our specifications and regulatory standards may delay or impair our ability to initiate or complete our clinical trials, obtain and maintain regulatory approvals or commercialize approved products.

We do not own or operate manufacturing facilities for the production of clinical or commercial quantities of our product candidates, and we lack the resources and the capabilities to do so. As a result, we currently rely, and expect to rely for the foreseeable future, on third-party manufacturers to supply us with pegozafermin and any future product candidates. We currently have a sole source relationship with BTPH pursuant to which they supply us with pegozafermin. If there should be any disruption in our supply arrangement with BTPH, including any adverse events affecting BTPH, it could have a negative effect on the clinical development of pegozafermin and other operations while we work to identify and qualify an alternate supply source. In addition, we will require large quantities of pegozafermin for large clinical trials and to commercialize pegozafermin. Our current manufacturer may not be able to scale production to the larger quantities. We have identified a manufacturing partner for commercial-scale manufacturing, however, we cannot guarantee that such partner will be able to scale up and produce the quantities we would require to commercialize pegozafermin.

We do not have a long-term supply agreement with any third-party manufacturer. Reliance on third-party manufacturers entails risks to which we would not be subject if we manufacture product candidates or products ourselves. For example, if we do not maintain our key manufacturing relationships, we may fail to find replacement manufacturers or develop our own manufacturing capabilities in a timely manner or at all, which could delay or impair our ability to obtain regulatory approval for our products and substantially increase our costs or deplete profit margins, if any. If we do find replacement manufacturers, we may not be able to enter into agreements with them on terms and conditions favorable to us, and there could be a substantial delay before new facilities could be qualified and registered with the FDA and other comparable foreign regulatory authorities.

We have begun producing certain of the reagents required for the glycoPEGylation at BTPH using the know-how transferred to us from Teva Pharmaceutical Industries Ltd (“Teva”) under our Reagent Supply and Technology Transfer Agreement. We have not completed the manufacturing process for all these reagents and cannot guarantee that we will be able to produce them successfully, or scale up our production for the quantities needed for commercialization.

Teva continues to supply us with certain reagents and will continue to do so until December 31, 2022. We expect the manufacturing of such reagents will be transferred to a new supplier prior to the end of 2022. Any complications arising under our agreement with Teva or any difficulties securing a new supplier could considerably delay the manufacture of pegozafermin. Any significant delay in the acquisition or decrease in the availability of these raw materials from Teva or any new supplier could considerably delay the manufacture of pegozafermin, which could adversely impact the timing of any planned trials or the regulatory approvals of pegozafermin.

We rely on third-party vendors for our assay development and testing. If such third-party vendors are unable to successfully produce or test such assays, it may substantially increase our cost or could adversely impact the timing of any planned trials or the regulatory approvals of pegozafermin.

The FDA and other comparable foreign regulatory authorities require manufacturers to register manufacturing facilities. The FDA and other comparable foreign regulatory authorities also inspect these facilities to confirm compliance with cGMP. We have little to no control regarding the occurrence of third-party manufacturer incidents. Any failure to comply with cGMP requirements or other FDA or comparable foreign regulatory requirements could adversely affect our clinical research activities and our ability to develop pegozafermin or any future product candidates and market our products following approval. Our sole source supplier, BTPH, has not yet manufactured a commercial product, and as a result, has not been subject to inspection by the FDA and other comparable foreign regulatory authorities.

Our current and anticipated future dependence upon others for the manufacture of our product candidates may adversely affect our future profit margins and our ability to develop our product candidates and commercialize any products that receive regulatory approval on a timely basis. Supply chain issues, including those resulting from the COVID-19 pandemic and the ongoing war in Ukraine, may affect our third-party vendors and cause delays. 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. For example, in the event that we need to switch our third-party manufacturer of pegozafermin from BTPH, which is our sole manufacturing source for pegozafermin, we anticipate that the complexity of the glycoPEGylation manufacturing process may materially impact the amount of time it may take to secure a replacement manufacturer. The delays associated with the verification of a new manufacturer, if we are able to identify an alternative source, could negatively affect our ability to develop product candidates in a timely manner or within budget.

Pegozaferminandany future product candidatesmay cause undesirableside effectsor have other propertiesthat could delay or preventtheirregulatoryapproval or limitthe commercialprofileof anapproved label.

Undesirable side effects caused by ~~BIO89-100~~pegozafermin or any future product candidates could cause us or regulatory authorities to interrupt, 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 comparable foreign regulatory authorities. Additional clinical studies may be required to evaluate the safety profile of ~~BIO89-100~~pegozafermin or any future product candidates. As with other drugs, we have seen evidence of adverse effects in animal and human studies and it is possible that other adverse effects will become apparent in ongoing or future animal or human safety studies. It may be difficult to discern whether certain events or symptoms observed during our clinical trials or by patients using our approved products are related to ~~BIO89-100~~pegozafermin or any future product candidates or approved products or some other factor. As a result, we and our development programs may be negatively affected even if such events or symptoms are ultimately determined to be unlikely related to ~~BIO89-100~~pegozafermin or any future product candidates or approved products. Further, we expect that ~~BIO89-100~~pegozafermin will require multiple administrations via subcutaneous injection in the course of a clinical trial. This chronic administration increases the risk that rare adverse events or chance findings are discovered in the commercial setting, where ~~BIO89-100~~pegozafermin would be a~~dministered~~administered to more patients or for greater periods of time, that were not uncovered by our clinical drug development programs.

We are developingpegozaferminfor the treatmentof NASH, an indication for which there are no approved products. This makes it difficultto predictthe timingandcostsof the clinicaldevelopmentof pegozaferminfor the treatmentof NASH.

We are developing ~~BIO89-100~~pegozafermin for the treatment of NASH, an indication for which there are no approved products. ~~This makes it difficult to predict~~Although there are guidelines issued by the ~~timing and costs of~~FDA for the ~~clinical~~ development of ~~BIO89-100 for the treatment of NASH.~~

~~We are developing BIO89-100~~drugs for the treatment of NASH, ~~an indication for which there are no approved products. Because there is no established regulatory approval process~~ ~~for NASH,~~ the development of a novel product candidates such as ~~BIO89-100~~pegozafermin may be more expensive and take longer than for other, better known or extensively studied product candidates. As other companies are in later stages of clinical trials for their potential NASH therapies, we expect that the path for regulatory approval for NASH therapies may continue to evolve in the near term as these other companies refine their regulatory approval strategies and interact with regulatory authorities. Such evolution may impact our future clinical trial designs, including trial size and endpoints, in ways that we

cannot predicttoday. In particular, regulatory authority expectations about liver biopsy data may evolve especially as more information is published about the inherent variability in liver biopsy data. Certain of our competitors have ~~recently~~ experienced regulatory setbacks for NASH therapies following communications from the FDA. We currently do not know the impact, if any, that these setbacks could have on the path for regulatory approval for NASH therapies generally or for ~~BIO89-100.~~ pegozafermin. Furthermore, the histology endpoints from our Phase 2b ENLIVEN trial may not be accepted as primary endpoints for a pivotal Phase 3 trial or for FDA approval.

Our anticipateddevelopmentcostswould likelyincreaseif developmentof ~~BIO89-100~~pegozafermin or any futureproductcandidateis delayedbecauseweare requiredby the FDAto performstudiesor trialsin additionto, or differentfrom,those thatwecurrentlyanticipate.

We are also developing ~~BIO89-100~~pegozafermin for the treatment of SHTG. Clinical trials for the treatment of SHTG may be relatively costly and time consuming. The requirements for approval by the FDA and comparable foreign regulatory authorities may change over time and this may require changes to ongoing or future clinical trial designs that could impact timelines and cost.

Lack of efficacy, adverse events or undesirable side effects may emerge in clinical trials conducted by third parties developing FGF product candidates, which could adversely affect our stock price, our ability to attract additional capital and our development program.

Lack of efficacy, adverse events or undesirable side effects may emerge in clinical trials conducted by third parties developing FGF product candidates like ours. For example, ~~Bristol-Myers Squibb Company~~Novo Nordisk and Akero Therapeutics, Inc. are also developing FGF21 product candidates for the treatment of NASH. We have no control over their clinical trials or development program, and lack of efficacy, adverse events or undesirable side effects experienced by subjects in their clinical trials could adversely affect our stock price, our ability to attract additional capital and our clinical development plans for ~~BIO89-100~~pegozafermin or even the viability or prospects of ~~BIO89-100~~pegozafermin as a product candidate, including by creating a negative perception of FGF therapeutics by healthcare providers or patients.

Interim, topline and preliminary data from our clinical trials that we announce or publish 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 study or trial. We also make assumptions, estimations, calculations and conclusions as part of our analyses of data, and we may not have received or had the opportunity to fully and carefully evaluate all data. As a result, the topline 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. In addition, we may report interim analyses of only certain endpoints rather than all endpoints. 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.

We have relied on, and expect to continue to rely on, third-party manufacturers to produce BIO89-100 or any future product candidates. Any failure by a third-party manufacturer to produce acceptable product candidates for us pursuant to our specifications and regulatory standards may delay or impair our ability to initiate or complete our clinical trials, obtain and maintain regulatory approvals or commercialize approved products.

We do not own or operate manufacturing facilities for the production of clinical or commercial quantities of our product candidates, and we lack the resources and the capabilities to do so. As a result, we currently rely, and expect to rely for the foreseeable future, on third-party manufacturers to supply us with BIO89-100 and any future product candidates. We currently have a sole source relationship with BTPH pursuant to which they supply us with BIO89-100. If there should be any disruption in our supply arrangement with BTPH, including any adverse events affecting BTPH, it could have a negative effect on the clinical development of BIO89-100 and other operations while we work to identify and qualify an alternate supply source. In addition, ~~we will require large quantities of BIO89-100 for large clinical trials and to commercialize BIO89-100. Our current manufacturer~~ ~~may not be able to scale production to the larger quantities~~ ~~and we may not be able to find another manufacturer who has the capacity to~~ Themanufacture ~~a commercial-scale quantity of BIO89-100~~.

We have begun producing certain of the reagents required for the glycoPEGylation at BTPH using the know-how transferred to us from Teva Pharmaceutical Industries Ltd (“Teva”) under our Reagent Supply and Technology Transfer~~Agreement~~. We have not completed the manufacturing process for these reagents and cannot guarantee that we will be able to produce them successfully, or scale up our production for the quantities needed for commercialization.

Teva continues to supply us with certain reagents and will continue to do so until December 31, 2022. We expect the manufacturing of such reagents will be transferred to a new supplier prior to the end of 2022. Any complications arising under our agreement with Teva or any difficulties securing a new supplier could considerably delay the manufacture of BIO89-100. Any significant delay in the acquisition or decrease in the availability of these raw materials from Teva or any new supplier could considerably delay the manufacture of BIO89-100, which could adversely impact the timing of any planned trials or the regulatory approvals of BIO89-100.

The FDA and other comparable foreign regulatory authorities require manufacturers to register manufacturing facilities. The FDA and other comparable foreign regulatory authorities also inspect these facilities to confirm compliance with cGMP. We have little to no control regarding the occurrence of third-party manufacturer incidents. Any failure to comply with cGMP requirements or other FDA or comparable foreign regulatory requirements could adversely affect our clinical research activities and our ability to develop BIO89-100 or any future product candidates and market our products following approval. Our sole source supplier, BTPH, has not yet manufactured a commercial product, and as a result, has not been subject to inspection by the FDA and other comparable foreign regulatory authorities.

Our current and anticipated future dependence upon others for the manufacture of our product candidates may adversely affect our future profit margins and our ability to develop our product candidates and commercialize any products that receive regulatory approval on a timely basis. 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. For example, in the event that we need to switch our third-party manufacturer of BIO89-100 from BTPH, which is our sole manufacturing source for BIO89-100, we anticipate that the complexity of the glycoPEGylation manufacturing process may materially impact the amount of time it may take to secure a replacement manufacturer. The delays associated with the verification of a new manufacturer, if we are able to identify an alternative source, could negatively affect our ability to develop product candidates in a timely manner or within budget.

~~The manufacture~~ of biologicproducts is complexandweare subjectto many manufacturingrisks,any of whichcould substantiallyincreaseour costsandlimitsupply of our products.

Todate, ~~BIO89-100~~pegozafermin has been manufacturedby a singlethird-partymanufacturer,BTPH,solelyfor preclinicalstudiesand clinicaltrials.The processof manufacturing ~~BIO89-100,~~pegozafermin, and in particular,the glycoPEGylationprocess, is complex,highly regulated, subjectto severalrisks and requiressignificantexpertiseand capitalinvestment,includingthe developmentof advanced manufacturing techniquesand processcontrols.Manufacturersof biologicproductsoftenencounterdifficultiesin production, including difficultieswith productioncostsand yields,qualitycontrol,includingstabilityof the product, qualityassurancetesting,operatorerrorand shortagesof qualifiedpersonnel,as well as compliancewith strictly enforcedfederal,stateand foreignregulations.We cannot assureyou thatany stabilityor otherissuesrelatingto the manufactureof ~~BIO89-100~~pegozafermin will not occur in the future. We have limitedprocessdevelopmentcapabilitiesand have accessonly to externalmanufacturing capabilities.We do not have and wedo not currentlyplan to acquireor develop the facilitiesor capabilitiesto manufacturebulk drug substanceor filleddrug productfor use in human clinicaltrialsor commercialization.

We will require substantial additional capital to finance our operations, which may not be available to us on acceptable terms, or at all. As a result, we may not complete the development and commercialization of BIO89-100 or develop new product candidates.

~~As a clinical-stage biopharmaceutical company, our operations have consumed significant amounts of cash since our~~ ~~inception. We expect our research and development expenses to increase substantially in connection with our ongoing activities, particularly as we conduct~~ ~~clinical trials~~ ~~of and seek regulatory approvals for BIO89-100.~~ We~~believe~~ ~~that~~ ~~our existing cash, cash equivalents and short-term available-for-sale securities, together with the proceeds available from our line of credit pursuant to our Loan Agreement (as defined above),~~ ~~willfundourprojectedoperatingrequirements~~ ~~for a period of at least one year from the date of this Quarterly Report on Form 10-Q is filed with the SEC~~.

We will require additional capital to discover, develop, obtain regulatory approval for and commercialize BIO89-100 and any future product candidates. We do not have any committed external source of funds other than the unused portion of the line of credit available to us pursuant to the Loan Agreement. We expect to finance future cash needs through public or private equity or debt offerings or product collaborations. Additional capital may not be available in sufficient amounts or on reasonable terms, if at all. If we do not raise additional capital, we may not be able to expand our operations or otherwise capitalize on our business opportunities, our business and financial condition will be negatively impacted and we may need to: significantly delay, scale back or discontinue research and discovery efforts and the development or commercialization of any product candidates or cease operations altogether;

seek strategic alliances for research and development programs when we otherwise would not, or at an earlier stage than we would otherwise desire or on terms less favorable than might otherwise be available; or relinquish, or license on unfavorable terms, our rights to technologies or any product candidates that we otherwise would seek to develop or commercialize ourselves.

In addition, if BIO89-100 receives approval and is commercialized, we will be required to make milestone and royalty payments to Teva, from whom we acquired certain patents and intellectual property relating to BIO89-100, and from whom we licensed patents and know-how related to glycoPEGylation technology that is used in the manufacture of BIO89-100. For additional information regarding this license agreement, please see Note 5 of our accompanying condensed consolidated financial statements.

We face substantialcompetition,whichmay resultin others discovering,developingor commercializing competingproducts beforeor more successfullythan us.

The biopharmaceuticalindustryis intenselycompetitiveand subjectto rapidinnovationand significant technologicaladvancements.Our competitors includemultinationalpharmaceuticalcompanies,specializedbiotechnologycompanies,universitiesand other researchinstitutions.Anumberof biotechnologyand pharmaceuticalcompaniesare pursuingthe developmentor marketingof pharmaceuticalsthattargetthe samediseasesthatweare targeting. Certain of these companies have recently published positive data regarding their clinical trials, which may further increase the competition we face. Smalleror earlier-stage companiesmay also prove to be significantcompetitors,particularlythrough collaborativearrangementswith large,establishedcompanies.Given the high incidenceof NASHand SHTG, it is likelythatthe numberofcompaniesseekingto develop productsand therapiesfor the treatmentof liverand cardio-metabolicdiseases, such as NASHand SHTG, will increase.

Thereare numerouscurrentlyapproved therapiesfor treatingdiseasesotherthan NASHand some of thesecurrentlyapproved therapiesmay exerteffectsthatcould be similarto ~~BIO89-100~~pegozafermin in NASH. Many of theseapproved drugs are well-establishedtherapiesor productsand are widely acceptedby physicians,patientsand third-partypayors. Some of thesedrugs are branded and subjectto patentprotection,and othersare availableon a genericbasis.This may make it difficultfor us to differentiateour productsfromcurrentlyapproved therapies,which may adverselyimpactour businessstrategy. We expect thatif ~~BIO89-100~~pegozafermin or any futureproductcandidatesare approved, they will be pricedat a significantpremium over competitivegenericproducts,includingbranded genericproducts.Insurersand otherthird-partypayors may also encouragethe use of genericproductsor specificbranded products prior to utilization of ~~BIO89-100.~~ pegozafermin.In addition,many companiesare developingnewtherapeutics,and wecannot predictwhat the standardof care will be as ~~BIO89-100~~pegozafermin or any futureproductcandidatesprogressthrough clinicaldevelopment.In addition,to the extent ~~BIO89-100~~pegozafermin or any futureproductcandidatesare approved for liver or cardio-metabolicindications,such as SHTG, the commercialsuccessof our productswill also depend on our abilityto demonstratebenefitsover the then-prevailingstandardof care,includingdiet,exerciseand lifestylemodifications.

Further,if ~~BIO89-100~~pegozafermin or any futureproductcandidatesare approved for the treatmentof SHTG,wewill competewith currentlyapproved therapiesand therapiesfurtheralong in development.Our competitorsboth in the United Statesand abroad includelarge,well-establishedpharmaceuticaland genericcompanieswith significantlygreatername recognition.Our competitorsmay be able to chargelower pricesthan wecan, which may adverselyaffectour marketacceptance.Many of thesecompetitorshave greaterresourcesthan wedo, includingfinancial,productdevelopment,marketing,personneland otherresources.

If our competitorsmarketproductsthatare moreeffective,saferor cheaperthan our productsor that reachthe marketsooner than our products,wemay not achievecommercialsuccess.Many of our competitorshave substantiallygreaterfinancial,technical,human and otherresourcesthan wedo and may be betterequipped to develop, manufactureand markettechnologicallysuperiorproducts.Asa result,our competitorsmay obtainregulatoryapprovalof theirproductsmorerapidlythan wedo or may obtainpatentprotectionor otherintellectualpropertyrightsthatlimitour abilityto develop or commercializeour productcandidateor any futureproductcandidates.Our competitorsmay also develop and succeedin obtainingapprovalfor drugs thatare moreeffective,moreconvenient,morewidely used and less costlyor have a bettersafetyprofilethan our productsand thesecompetitorsmay also be moresuccessfulthan weare in manufacturingand marketingtheirproducts.

Unstable market and economic conditions may have serious adverse consequences on our business and financial condition.

Global credit and financial markets have experienced extreme disruptions at various points over the last few decades. If another such disruption in credit and financial markets and deterioration of confidence in economic conditions occurs, it may make any necessary debt or equity financing more difficult to complete, more costly, and more dilutive. Failure to secure any necessary financing in a timely manner and on favorable terms could have a material adverse effect on our growth strategy, financial performance and share price and could require us to delay or abandon development or commercialization plans. In addition, there is a risk that one or more of our service providers, manufacturers or other partners would not survive or be able to meet their commitments to us under such circumstances, which could directly affect our ability to attain our operating goals on schedule and on budget.

~~Our~~The 2021 Loan ~~and Security~~ Agreement ~~with Silicon Valley Bank (as amended, the “Loan Agreement”)~~ contains certain covenants that could adversely affect our operations and, if an event of default were to occur, we could be forced to repay any outstanding indebtedness sooner than planned and possibly at a time when we do not have sufficient capital to meet this obligation.

Pursuant to the 2021 Loan Agreement, we have pledged substantially all of our assets, other than our intellectual property rights, and have agreed that we may not sell or assign rights to our patents and other intellectual property without the prior consent of ~~Silicon Valley Bank (“SVB”).~~SVB. Additionally, the 2021 Loan Agreement contains certain affirmative and negative covenants that could prevent us from taking certain actions without the consent of our lenders. These covenants may limit our flexibility in operating our business and our ability to take actions that might be advantageous to us and our stockholders. The 2021 Loan Agreement also includes customary events of default, including, among other things, a change of control. Upon the occurrence and continuation of an event of default, all amounts due under the 2021 Loan Agreement become (in the case of a bankruptcy event), or may become (in the case of all other events of default and at the option of SVB), immediately due and payable. If an event of default under the 2021 Loan Agreement should occur, we could be required to immediately repay any outstanding indebtedness. If we are unable to repay such debt, the lenders would be able to foreclose on the secured collateral, including our cash accounts, and take other remedies permitted under the 2021 Loan Agreement. Even if we are able to repay any indebtedness on an event of default, the repayment of these sums may significantly reduce our working capital and impair our ability to operate as planned.

We may encounter difficulties in managing our growth, which could adversely affect our operations.

We are in the early stages of building the full team that we anticipate we will need to complete the development ~~BIO89-100~~pegozafermin and other future product candidates. As we advance our preclinical and clinical development programs for product candidates, seek

regulatory approval in the United States and elsewhere and increase the number of ongoing product development programs, we anticipate that we will need to increase our product development, scientific and administrative headcount. We will also need to establish commercial capabilities in order to commercialize any product candidates that may be approved. Such an evolution may impact our strategic focus and our deployment and allocation of resources. Our ability to manage our operations and growth effectively depends upon the continual improvement of our procedures, reporting systems and operational, financial and management controls. We may not be able to implement administrative and operational improvements in an efficient or timely manner and may discover deficiencies in existing systems and controls. In addition, in order to continue to meet our obligations as a public company and to support our anticipated long-term growth, we will need to increase our general and administrative capabilities. Our management, personnel and systems may experience difficulty in adjusting to our growth and strategic focus.

We must attractandretainhighly skilledemployeesin order to succeed. If weare not able to retainour current senior managementteamandour scientificadvisorsor continue to attractandretainqualified scientific,technicalandbusiness personnel, our business will suffer.

We may not be able to attractor retainqualifiedpersonneland consultantsdue to the intense competitionfor such individuals in the biotechnologyand pharmaceuticalindustries.If weare not able to attractand retainnecessarypersonneland consultantsto accomplishour businessobjectives,it may significantlyimpedethe achievementof our developmentand commercialobjectivesand our abilityto implementour businessstrategy. In addition, we are highly dependenton the development,regulatory, manufacturing, commercializationand financialexpertiseof the membersof our executiveteam,as well as otherkey employeesand consultants.If welose one or moreof our executiveofficersor otherkey employeesor consultants,our abilityto implementour businessstrategy successfullycould be seriouslyharmed.

We are developinga newdrug product formulationfor ~~BIO89-100~~ pegozaferminandwemay be unsuccessful.Anychanges in methodsof product candidatemanufacturingor formulationmay resultin the need to performnewclinical trials or obtain new drug product,whichwouldrequireadditionalcostsandcause delay.

Our current drug product comes in two formulations, frozen and liquid, with the latter being used in all new studies, beginning with our ENLIVEN study. We are developing a newdrug productformulationof ~~BIO89-100~~pegozafermin for late-stageclinicaltrialsand commercialization. ~~Our current drug product is stored as a frozen liquid and is therefore not well-suited to larger clinical trials or commercialization. We have developed a new refrigerated liquid formulation~~ ~~and have~~ ~~engaged a formulation development company to also explore a freeze-dried, or lyophilized, formulation.~~ We have commenced development of a pre-filled syringe for the newdrug productformulation and we also plan to begin development of a pen-typeautoinjector.There is no assurancethatwewill be successful in developinga newdrug productformulation, a pre-filled syringeor an autoinjectoron a timelybasisor at all, any ofwhich could impede our developmentand commercializationstrategyfor ~~BIO89-100.~~pegozafermin. The FDAor othercomparableforeign regulatoryauthoritiescould requirenonclinicalstudiesor clinicaltrialsto supportintroductionof any new formulation, pre-filled syringeand autoinjector, which could delay completionof clinicaltrials,requirethe conduct of bridging clinicaltrialsor the repetitionof one or moreclinicaltrials,increaseour clinicaltrialcosts,delay approvalof ~~BIO89-100~~pegozafermin and jeopardizeour abilityto commenceproductsalesand generaterevenuefrom ~~BIO89-100,~~pegozafermin, if approved.

We rely on third parties for certain aspects of our product candidate development process and we may not be able to obtain and maintain the third-party relationships that are necessary to develop, commercialize and manufacture some or all of our product candidates.

We expect to depend on collaborators, partners, licensees, clinical investigators, ~~CROs,~~contract research organizations, manufacturers and other third parties to support our discovery efforts, to formulate product candidates, to conduct clinical trials for some or all of our product candidates, to manufacture clinical and commercial scale quantities of our drug substance and drug product and to market, sell and distribute any products we successfully develop. Anyof thesethirdpartiesmay terminatetheir engagementswith us at any time.If weneed to enterinto alternativearrangements,it would delay our product developmentactivitiesand such alternativearrangementsmay not be availableon termsacceptableto us. We also expectto relyon otherthirdpartiesto storeand distributedrug suppliesfor our clinicaltrials. Anyperformancefailureon the partof our distributorscould delay clinicaldevelopment,marketingapproval and/orcommercializationof ~~BIO89-100~~pegozafermin or any futureproductcandidates,producingadditionallossesand deprivingus of potentialrevenue.

Business disruptions could seriously harm our future revenue and financial condition and increase our costs and expenses.

Our operations, and those of our contract research organizations, CMO, suppliers, and other contractors and consultants, could be subject to earthquakes, power shortages, telecommunications failures, water shortages, floods, hurricanes, typhoons, fires, extreme weather conditions, acts of war, medical pandemics or epidemics, such as the novel coronavirus, and other natural or man-made disasters or business interruptions. The occurrence of any of these business disruptions could seriously harm our operations and financial condition and increase our costs and expenses.

If we fail to develop and commercialize additional product candidates, we may be unable to grow our business.

Although the developmentand commercializationof ~~BIO89-100~~pegozafermin is currentlyour primaryfocus, as part of our longer-termgrowth strategy,we plan to evaluatethe developmentand commercializationof other therapiesrelatedto NASHand otherliverand cardio-metabolicdiseases.The successof thisstrategydepends primarilyupon our abilityto identifyand validatenew therapeuticcandidates,and to identify,develop and commercializenew drugs and biologics.Our researcheffortsmay initiallyshow promisein discoveringpotential new drugs and biologics,yet failto yieldproductcandidatesfor clinicaldevelopmentfor a numberof reasons.

We may use our limitedfinancialandhumanresourcesto pursue a particularresearchprogram or product candidatethat is ultimatelyunsuccessfulor lesssuccessfulthan other programsor product candidatesthat we may have forgone or delayed.

Because we have limitedpersonneland financialresources,we may foregoor delay the developmentof certainprogramsor productcandidatesthatlaterprove to have greatercommercialpotentialthan the programsor productcandidatesthatwe do pursue. Our resourceallocationdecisionsmay cause us to failto capitalizeon viablecommercialproductsor profitablemarketopportunities.Our spending on currentand futureresearchand developmentprogramsfor productcandidatesmay not yieldany commerciallyviableproducts.Similarly,our decisionsto delay or terminatedrug developmentprogramsmay also be incorrectand could cause us to miss valuableopportunities.

We may seek to establish commercial collaborations for our product candidates, and, if we are not able to establish them on commercially reasonable terms, we may have to alter our development and commercialization plans.

Our drug development programs and the potential commercialization of our product candidates will require substantial additional cash to fund expenses. We may decide to collaborate with other pharmaceutical and biotechnology companies for the development and potential commercialization of our product candidates. Collaborations are complex and time-consuming to negotiate and document. 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 its development program or one or more of our other development programs, delay its 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.

We may not be successful in our efforts to identify, in-license or acquire, discover, develop or commercialize additional product candidates.

We may seek to identify, in-license or acquire, discover, develop and commercialize additional product candidates. We cannot assure you that our effort to in-license or acquire additional product candidates will be successful. Even if we are successful in in-licensing or acquiring additional product candidates, their requisite development activities may require substantial resources, and we cannot assure you that these development activities will result in regulatory approvals.

Ourinternationaloperationsmay expose us to business, regulatory,political,operational,financial,pricing andreimbursementrisksassociatedwith doing business outsideof the United States.

Our use of our internationalfacilities ~~subject~~ subjectsus to U.S.and foreigngovernmentaltrade,importand export,and customsregulationsand laws. Compliancewith theseregulationsand laws is costlyand exposes us to penaltiesfor non-compliance.Doing businessinternationallypotentiallyinvolvesa numberof risks, any of which could harmour ongoing internationalclinicaloperationsand supply chain, as well as any futureinternationalexpansionand operationsand, consequently,our business,financialcondition, prospectsand resultsof operations.

Product liability lawsuits against us could cause us to incur substantial liabilities and to limit commercialization of any products that we may develop.

We face an inherent risk of product liability exposure related to the testing of our product candidates in human clinical trials and will face an even greater risk if we commercialize any resulting products. Product liability claims may be brought against us by subjects enrolled in our clinical trials, patients, or others using our products. Our clinical trial liability insurance coverage may not adequately cover all liabilities that we may incur.

Ouremployees,contractors,vendors, principalinvestigators,consultantsandfuture partnersmay engage in misconductor other improperactivities,including noncompliancewith regulatorystandards andrequirements andinsidertrading.

We are exposed to the risk of fraud or other misconduct by our employees, contractors, vendors, principal investigators, consultants or future partners. Misconduct by these parties could include failures to comply with FDA regulations, to provide accurate

information to the FDA, to comply with federal and state healthcare fraud and abuse laws and regulations, to report financial information or data timely, completely or accurately, or to disclose unauthorized activities to us. Most states also have statutes or regulations similar to these federal laws, which may apply to items such as pharmaceutical products and services reimbursed by private insurers. We and/or our future partners may be subject to administrative, civil and criminal sanctions for violations of any of these laws.

We depend on our information technology systems and those of our third-party collaborators, service providers, contractors or consultants. Our internal computer systems, or those of our third-party collaborators, service providers, contractors or consultants, may fail or suffer security breaches, disruptions, or incidents, which could result in a material disruption of our development programs or loss of data or compromise the privacy, security, integrity or confidentiality of sensitive information related to our business and have a material adverse effect on our reputation, business, financial condition or results of operations.

In the ordinarycourseof our business,wecollect,storeand transmitlargeamountsof confidential information,includingintellectualproperty,proprietarybusinessinformationand personalinformation.Our internaltechnologysystemsand infrastructure,and those of our currentor futurethird-partycollaborators, serviceproviders,contractorsand consultantsare vulnerableto damagefromcomputerviruses,unauthorized accessor use resultingfrommalware,naturaldisasters,terrorism,war and telecommunicationand electrical failures,denial-of-serviceattacks,cyber-attacksor cyber-intrusionsover the Internet,hacking, phishingand other socialengineeringattacks,personsinsideour organizations ~~(including~~ (includingemployeesor contractors),loss or theft,or personswith accessto systemsinsideour organization. ~~While~~ From time to ~~our knowledge~~time, we ~~have not experienced any material system failure, accident or security breach to date we have been~~are subject to periodic phishing attempts. In the third quarter of 2021, we discovered a business email compromise caused by phishing. The phishing attack did not result in the misappropriation of any funds. Even though we are implementing remedial measures promptly following this incident and do not believe that it had a material adverse effect on our business, we cannot guarantee that our implemented remedial measures will prevent additional related, as well as unrelated, incidents.If a material systemfailure,accidentor securitybreach were to occur and cause interruptionsin our operationsor the operationsof third-partycollaborators,serviceproviders, contractorsand consultants,it could resultin a materialdisruptionof our developmentprogramsand significant reputational,financial,legal,regulatory,businessor operationalharm.

Tothe extentthatany realor perceivedsecuritybreachaffectsour systems ~~(or~~(or those of our third-partycollaborators,serviceproviders,contractorsor consultants),or resultsin the loss of or accidental,unlawfulor unauthorizedaccessto, use of, releaseof, or otherprocessingof personallyidentifiable informationor damageto our data or applicationsor otherdata or applicationsrelatingto our technologyor productcandidates,or inappropriatedisclosureof confidentialor proprietaryinformation,wecould incur liabilitiesand the furtherdevelopmentof our productcandidatescould be delayed.Anyfailureor perceivedfailureby us or any third-partycollaborators,serviceproviders,contractorsor consultantsto complywith our privacy,confidentiality,data securityor similarobligations,or any data security incidentsor othersecuritybreachesthatresultin the accidental,unlawfulor unauthorizedaccessto, use of, releaseof, processingof, or transferof sensitiveinformation,includingpersonallyidentifiableinformation,may resultin negativepublicity,harmto our reputation,governmentalinvestigations,enforcementactions,regulatory fines,litigationor publicstatementsagainstus, could cause thirdpartiesto lose trustin us or could resultin claimsby thirdparties,includingthose thatassertthatwehave breachedour privacy,confidentiality,data securityor similarobligations,any of which could have a materialadverseeffecton our reputation,business, financialconditionor resultsof operations.

~~BIO89-100~~ Pegozaferminhas not receivedregulatoryapproval. If weare unable to obtain regulatoryapprovalsto market ~~BIO89-100~~ pegozaferminor any future product candidates,our business will be adverselyaffected.

We do not expect ~~BIO89-100~~pegozafermin or any future product candidate to be commercially available for several years, if at all. ~~BIO89-100~~Pegozafermin is and any future product candidate will be subject to strict regulation by regulatory authorities in the United States and in other countries. We cannot market any product candidate until we have completed all necessary preclinical studies and clinical trials and have obtained the necessary regulatory approvals. We do not know whether regulatory agencies will grant approval for ~~BIO89-100~~pegozafermin or any future product candidate. Even if we complete preclinical studies and clinical trials successfully, we may not be able to obtain regulatory approvals or we may not receive approvals to make claims about our products that we believe to be necessary to effectively market our products. Data obtained from preclinical studies and clinical trials is subject to varying interpretations that could delay, limit or prevent regulatory approval, and failure to comply with regulatory requirements or inadequate manufacturing processes are

examplesof otherproblemsthatcould preventapproval.The regulatoryauthoritiesin the United Statesand the EUhave not approved any productsfor the treatmentof NASH,and while thereare ~~recent~~guidelinesissuedby the FDAfor the developmentof drugs for the treatmentof NASHand aan FDAsurrogateendpointtablefor drug approvalthatincludesSHTG, it is unclearwhether the requirementsfor approvalwill change in the future.Anysuch changes may requireus to conduct newtrialsthatcould delay our timeframeand increasethe costsof our programsrelatedto ~~BIO89-100~~pegozafermin or any futureproductcandidatefor the treatmentof NASHor SHTG. Whilethe FDAhas approved reductionintriglycerideslevelsas a surrogateendpointfor the fullapprovalof drugs for the treatmentof SHTG,it is unclear whether thisendpointwill apply to any productcandidatesthatwedevelop. If such endpointis not deemedto apply to our productcandidates,it would delay our developmenttimelineand increasethe costsof our programs for the treatmentof SHTG. We have not had any discussions with the FDAregardinga surrogateendpointoracceleratedapprovalregulations.However, wecurrentlyexpectthatour SHTGprogramwould be subjectto smallerclinicaltrialsand thatwemay expecta relativelyquicker overalldevelopmenttimelinefor thisindication. These expectationsare based on a publishedFDAsurrogate

endpointtablefor drug approvalthatincludes SHTG, as well as the developmentpath followedby othercompaniesthatdevelopedan SHTGtherapy.

Evenif weare able to obtain regulatoryapprovalsfor ~~BIO89-100~~ pegozaferminor any future product candidate,if they exhibitharmfulside effectsafterapproval, our regulatoryapprovalscould be revoked or otherwisenegatively impacted,andwecould be subjectto costlyanddamaging product liabilityclaims.

Even if we receive~~regulatoryapprovalforBIO89-100~~ or ~~any futureproductcandidates,~~ we ~~willhavetestedthem~~ in ~~only~~ a ~~smallnumber~~ of ~~patientsduringourclinicaltrials.~~ If ~~ourapplicationsformarketingareapprovedandmorepatientsbegin~~ to ~~useourproduct,new risksandsideeffectsassociatedwithourproductsmay~~be ~~discovered.~~ As a ~~result,regulatoryauthoritiesmayrevoketheirapprovals.~~ We ~~havenothadanydiscussionswiththeFDA regarding~~ a ~~surrogateendpoint~~ or ~~acceleratedapprovalregulations.However,based~~ on ~~recentguidelinesissued~~ by ~~theFDA forthedevelopment~~ of ~~drugsforthetreatment~~ of ~~NASH,~~ if ~~BIO89-100~~ is ~~approved~~ by ~~theFDAbased~~ on a ~~surrogateendpointpursuant~~ to ~~section506(c)~~ of ~~theFederalFood,Drug,andCosmeticActandtheacceleratedapprovalregulations(21C.F.R.part314,subpart~~ ~~H; 21~~ ~~C.F.R.part601,subpartE),consistentwithFDA guidance,~~ we ~~will~~ be ~~required~~ to ~~conductadditionalclinicaltrialsestablishingclinicalbenefit~~ on ~~theultimateoutcome~~ of ~~NASH.~~ If ~~BIO89-100~~ is ~~approved~~ by ~~theFDA forthetreatment~~ of ~~SHTG based~~ ~~on an~~ ~~endpoint~~ of ~~thereduction~~ of ~~triglycerides,theFDA maystillrequire~~ a ~~cardiovascularoutcomesstudy~~ as ~~part~~ of a ~~post-marketingauthorizationcommitment.Such~~ a ~~studywould~~ be ~~timeconsumingandcostlyand~~we~~cannotguaranteethat~~ we ~~willseepositiveresults, which could result~~ in ~~therevocation~~ of ~~theapproval. Additionally, wemay~~ be ~~required~~ to~~conductadditionalclinicaltrials, makechanges~~ in ~~labeling~~ of ~~ourproduct, reformulateourproduct~~ or ~~makechangesandobtainnew approvalsforourandoursuppliers’manufacturingfacilitiesforBIO89-100andanyfutureproductcandidates.~~ We ~~mighthave~~ to ~~withdraw~~ or ~~recallourproductsfromthemarketplace.~~ We ~~may alsoexperience~~ a ~~significantdrop~~ in ~~thepotentialsales~~ of ~~ourproduct~~ if ~~andwhenregulatoryapprovalsforsuchproductarerevoked.~~ As a ~~result,~~ we ~~mayexperienceharm~~ to ~~ourreputation~~ in ~~themarketplace~~ or ~~becomesubjectto lawsuits,includingclassactions.Any~~ of ~~theseresultscoulddecrease~~ or ~~preventanysales~~ of ~~ourapprovedproduct~~or ~~substantiallyincreasethecostsandexpenses~~ of ~~commercializingandmarketingourproduct.~~

~~The regulatory approval processes of the FDA and comparable foreign regulatory authorities are lengthy, time-consuming and inherently unpredictable. Our inability to obtain~~ regulatory approval for ~~BIO89-100~~pegozafermin or any future product candidates, we will have tested them in only a small number of patients during our clinical trials. If our applications for marketing are approved and more patients begin to use our product, new risks and side effects associated with our products may be discovered. As a result, regulatory authorities may revoke their approvals. We have not had any discussions with the FDA regarding a surrogate endpoint or accelerated approval regulations. However, based on recent guidelines issued by the FDA for the development of drugs for the treatment of NASH, if pegozafermin is approved by the FDA based on a surrogate endpoint pursuant to section 506(c) of the Federal Food, Drug, and Cosmetic Act and the accelerated approval regulations (21 C.F.R. part 314, subpart H; 21 C.F.R. part 601, subpart E), consistent with FDA guidance, we will be required to conduct additional clinical trials establishing clinical benefit on the ultimate outcome of NASH. If pegozafermin is approved by the FDA for the treatment of SHTG based on an endpoint of the reduction of triglycerides, the FDA may still require a cardiovascular outcomes study as part of a post-marketing authorization commitment. Such a study would be time consuming and costly and we cannot guarantee that we will see positive results, which could result in the revocation of the approval. Additionally, we may be required to conduct additional clinical trials, make changes in labeling of our product, reformulate our product or make changes and obtain new approvals for our and our suppliers’ manufacturing facilities for pegozafermin and any future product candidates. We might have to withdraw or recall our products from the marketplace. We may also experience a significant drop in the potential sales of our product if and when regulatory approvals for such product are revoked. As a result, we may experience harm to our reputation in the marketplace or become subject to lawsuits, including class actions. Any of these results could decrease or prevent any sales of our approved product or substantially increase the costs and expenses of commercializing and marketing our product.

Theregulatoryapproval processesof the FDAandcomparableforeignregulatoryauthoritiesare lengthy, time-consumingandinherentlyunpredictable.Ourinabilityto obtain regulatoryapproval for pegozaferminor any future product candidateswouldsubstantiallyharm our business.

Currently, we do not have any product candidates that have received regulatory approval. The time required to obtain approval from the FDA and comparable foreign regulatory authorities is unpredictable but typically takes many years following the commencement of preclinical studies and clinical trials and depends upon numerous factors, including the substantial discretion of the regulatory authorities. 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 development and may vary among jurisdictions. It is possible that none of ~~BIO89-100~~pegozafermin or any future product candidates will ever obtain regulatory approval. ~~BIO89-100~~Pegozafermin or any future product candidate could fail to receive regulatory approval from the FDA or comparable foreign regulatory authorities for many reasons,, including those referenced in Part I, Item 1. “Business—Government Regulation and Product ~~Approval~~”.Approval” in our Annual Report on Form 10-K for the year ended December 31, 2021. If we were to obtain approval, regulatory authorities may approve any of our product candidates for fewer or more limited indications than we request, may grant approval contingent on the performance of costly post-marketing clinical trials or may approve a product candidate with a label that does not include the labeling claims necessary or desirable for the successful commercialization of the product candidate.

Evenif ~~BIO89-100~~pegozafermin or any future product candidatereceivesregulatoryapproval, it may stillface future developmentandregulatorydifficulties.

Even if we obtained regulatory approval for a product candidate, it would be subject to ongoing requirements by the FDA and comparable foreign regulatory authorities governing the manufacture, quality control, further development, labeling, packaging, storage, distribution, safety surveillance, import, export, advertising, promotion, recordkeeping and reporting of safety and other post-market information. In addition, manufacturers of drug products and their facilities are subject to continual review and periodic inspections by the FDA and other regulatory authorities for compliance with cGMP, regulations and standards. If we or a regulatory agency discover 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, a regulatory agency may impose restrictions on that product, the manufacturing facility or us, including requiring recall or withdrawal of the product from the market or suspension of manufacturing. If we, our product candidates or the manufacturing facilities for our product candidates fail to comply with applicable regulatory requirements, or undesirable side effects caused by such products are identified, a regulatory agency may: issue safety alerts, Dear Healthcare Provider letters, press releases or other communications containing warnings about such product; mandate modifications to promotional materials or require us to provide corrective information to healthcare practitioners; require that we conduct post-marketing studies; require us to enter into a consent decree, which can include imposition of various fines, reimbursements for inspection costs, required due dates for specific actions and penalties for noncompliance; seek an injunction or impose civil or criminal penalties or monetary fines; suspend marketing of, withdraw regulatory approval of or recall such product; suspend any ongoing clinical studies; refuse to approve pending applications or supplements to applications filed by us; suspend or impose restrictions on operations, including costly new manufacturing requirements; or seize or detain products, refuse to permit the import or export of products or require us to initiate a product recall. The occurrence of any event or penalty described above may inhibit our ability to commercialize our products and generate product revenue.

Oursuccessdepends uponour abilityto obtain andmaintainintellectualpropertyprotectionfor our products andtechnologies.

Our success will depend in significant part on our current or future licensors’, licensees’ or collaborators’ ability to establish and maintain adequate protection of our owned and licensed intellectual property covering the product candidates we plan to develop, and the ability to develop these product candidates and commercialize the products resulting therefrom, without infringing the intellectual property rights of others. In addition to taking other steps to protect our intellectual property, we hold issued patents, we have applied for patents, and we intend to continue to apply for, patents with claims covering our technologies, processes and product candidates when and where we deem it appropriate to do so. We have filed numerous patent applications both in the United States and in certain foreign jurisdictions to obtain patent rights to inventions we have discovered, with claims directed to compositions of matter, methods of use and other technologies relating to our programs. There can be no assurance that any of these patent applications will issue as patents or, for those applications that do mature into patents, that the claims of the patents will exclude others from making, using or selling our product candidates or products that compete with or are similar to our product candidates. In countries where we have not sought and do not seek patent protection, third parties may be able to manufacture and sell our product candidates without our permission, and we may not be able to stop them from doing so.

With respect to patent rights, we do not know whether any of the pending patent applications for any of our product candidates will result in the issuance of patents that effectively protect our technologies, processes and product candidates, or if any of our issued patents or our current or future licensors’, licensees’ or collaborators’ issued patents will effectively prevent others from commercializing competitive technologies, processes and products. We cannot be certain that we or our current or future licensors, licensees or collaborators were the first to make the inventions claimed in our owned or licensed patents or pending patent applications, or that we or our current or future licensors, licensees or collaborators were the first to file for patent protection of such inventions.

Any changes we make to our ~~BIO89-100~~pegozafermin or any future product candidates to cause them to have what we view as more advantageous properties may not be covered by our existing patents and patent applications, and we may be required to file new applications and/or seek other forms of protection for any such altered product candidates. The patent landscape surrounding the technology underlying our product candidates is crowded, and there can be no assurance that we would be able to secure patent protection that would adequately cover an alternative to ~~BIO89-100~~pegozafermin or any future product candidates.

We and our current or future licensors, licensees or collaborators may not be able to prepare, file and prosecute all necessary or desirable patent applications at a reasonable cost or in a timely manner. It is also possible that we or our current or future licensors, licensees or collaborators will fail to identify patentable aspects of inventions made in the course of development and commercialization activities before it is too late to obtain patent protection for them. Moreover, in some circumstances, we may not have the right to control the preparation, filing and prosecution of patent applications, or to maintain or enforce the patents, covering technology that we license from or license to third parties and may be reliant on our current or future licensors, licensees or collaborators to perform these activities, which means that these patent applications may not be prosecuted, and these patents enforced, in a manner consistent with the best interests of our business. If our current or future licensors, licensees or collaborators fail

to establish,maintain,protector enforcesuch patentsand otherintellectualpropertyrights,such rightsmay be reducedor eliminated.If our currentor futurelicensors,licenseesor collaboratorsare not fullycooperativeor disagreewith us as to the prosecution,maintenanceor enforcementof any patentrights,such patentrightscould be compromised.

Similar to the patent rights of other biotechnology companies, the scope, validity and enforceability of our owned and licensed patent rights generally are highly uncertain and involve complex legal and factual questions. The issuance of a patent is not conclusive as to its inventorship, scope, validity or enforceability, and our patents may be challenged in the courts or patent offices in the United States and abroad. In recent years, these areas have been the subject of much litigation in the industry. As a result, the issuance, scope, validity, enforceability and commercial value of our and our current or future licensors’, licensees’ or collaborators’ patent rights are highly uncertain. Our and our current or future licensors’, licensees’ or collaborators’ pending and future patent applications may not result in patents being issued that protect our technology or product candidates, or products resulting therefrom, in whole or in part, or that effectively prevent others from commercializing competitive technologies and products. The patent examination process may require us or our current or future licensors, licensees or collaborators to narrow the scope of the claims of pending and future patent applications, which would limit the scope of patent protection that is obtained, if any. Our and our current or future licensors’, licensees’ or collaborators’ patent applications cannot be enforced against third parties practicing the technology that is currently claimed in such applications unless and until a patent issues from such applications, and then only to the extent the claims that issue are broad enough to cover the technology being practiced by those third parties.

Furthermore, given the amount of time required for the development, testing and regulatory review of new product candidates, patents protecting such candidates might expire before or shortly after the resulting products are commercialized. As a result, our owned and in-licensed patents may not provide us with sufficient rights to exclude others from commercializing products similar or identical to ours. We expect to seek extensions of patent terms for our issued patents, where available. The applicable authorities, including the FDA in the United States, and any comparable foreign regulatory authorities, may not agree with our assessment of whether such extensions are available, and may refuse to grant extensions to our patents, or may grant more limited extensions than we request. In addition, we may not be granted an extension because of, for example, failing to apply within applicable deadlines, failing to apply prior to the expiration of relevant patents or otherwise failing to satisfy applicable requirements.

We may not be able to protectour intellectualpropertyrightsthroughout the world.

The legal protection afforded to inventors and owners of intellectual property in countries outside of the United States may not be as protective or effective as that in the United States and we may, therefore, be unable to acquire and enforce intellectual property

rights outside the United States to the same extent as in the United States. Whether filed in the United States or abroad, our patent applications may be challenged or may fail to result in issued patents. Filing, prosecuting, enforcing and defending patents on product candidates in all countries throughout the world would be prohibitively expensive, and our intellectual property rights in some countries outside the United States are less extensive than those 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 certain 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. Competitors may use technologies in jurisdictions where we have not obtained 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 ~~BIO89-100~~pegozafermin or any future product candidates and our patents or other intellectual property rights may not be effective or sufficient to prevent them from competing.

We rely on a license from Teva and a sublicense from ratiopharm to patents and know-how related to glycoPEGylation technology that are used in the development, manufacture and commercialization of ~~BIO89-100.~~pegozafermin. Any termination or loss of significant rights, including the right to glycoPEGylation technology, or breach, under these agreements or any future license agreement related to our product candidates, would materially and adversely affect our ability to continue the development and commercialization of the related product candidates.

In April 2018, we entered into an Asset Transfer and License Agreement (the “FGF21 Agreement”) with Teva under which we acquired certain patents, intellectual property and other assets relating to Teva’s glycoPEGylated FGF21 program, including ~~BIO89-100.~~pegozafermin. Under this agreement, we were granted a perpetual, non-exclusive (but exclusive as to ~~BIO89-100)~~pegozafermin), non-transferable, worldwide license to patents and know-how related to glycoPEGylation technology used in the development, manufacture and commercialization of ~~BIO89-100~~pegozafermin and products containing ~~BIO89-100.~~pegozafermin. The FGF21 Agreement also contains numerous covenants with which we must comply, including the utilization of commercially reasonable efforts to develop and ultimately commercialize ~~BIO89-100,~~pegozafermin, as well as certain reporting covenants and the obligation to make royalty payments, if and when ~~BIO89-100~~pegozafermin is approved for commercialization. Our failure to satisfy any of these covenants could result in the termination of the FGF21 Agreement. In addition, we entered into a Sublicense Agreement with ratiopharm (the “ratiopharm Sublicense”), under which we were granted a perpetual, exclusive,

worldwide sublicenseto patentsand know-howrelatedto glycoPEGylationtechnologyused in the development, manufactureand commercializationof ~~BIO89-100~~pegozafermin and productscontaining~~BIO89-100.~~ pegozafermin. Terminationof the FGF21Agreementor the ratiopharmSublicensewill impactour rightsunder the intellectualpropertylicensedto us by Teva and ratiopharm,respectively, includingour licenseto glycoPEGylationtechnology,but will not affectour rightsunder the assetsassignedto us.

Beyond this agreement, our commercial success will also depend upon our ability, and the ability of our licensors, to develop, manufacture, market and sell our product candidates and use our proprietary technologies without infringing the proprietary rights of third parties. A third party may hold intellectual property rights, including patent rights, that are important or necessary to the development of our product candidates. As a result, we may enter into additional license agreements in the future. If we fail to comply with the obligations under these agreements, including payment and diligence obligations, our licensors may have the right to terminate these agreements, in which event we may not be able to develop, manufacture, market or sell any product that is covered by these agreements or to engage in any other activities necessary to our business that require the freedom to operate afforded by the agreements, or we may face other penalties under the agreements.

We may be unable to obtain intellectualpropertyrightsor technologynecessaryto developandcommercialize ~~BIO89-100~~ pegozaferminandany future product candidates.

The patent landscape around our programs is complex, and we are aware of several third-party patents and patent applications containing subject matter that might be relevant to ~~BIO89-100.~~pegozafermin. Depending on what claims ultimately issue from these patent applications, and how courts construe the issued patent claims, as well as depending on the ultimate formulation and method of use of ~~BIO89-100~~pegozafermin or any future product candidates, we may need to obtain a license to practice the technology claimed in such patents. There can be no assurance that such licenses will be available on commercially reasonable terms, or at all.

We may becomeinvolvedin lawsuitsor other proceedingsto protector enforceour intellectualproperty, whichcould be expensive,time-consumingandunsuccessfulandhave a materialadverseeffectonthe success of our business.

Third parties may infringe our patents or misappropriate or otherwise violate our intellectual property rights. In the future, we may initiate legal proceedings to enforce or defend our intellectual property rights, to protect our trade secrets or to determine the validity or scope of intellectual property rights we own or control. Also, third parties may initiate legal proceedings against us to challenge the validity or scope of intellectual property rights we own, control or to which we have rights. An adverse result in any litigation proceeding could put one or more of our patents at risk of being invalidated, narrowed, held unenforceable or interpreted in such a manner that would not preclude third parties from entering the market with competing products.

Third-party pre-issuance submission of prior art to the USPTO, or opposition, derivation, revocation, reexamination, interpartes review or interference proceedings, or other pre-issuance or post-grant proceedings or other patent office proceedings or litigation in the United States or other jurisdictions provoked by third parties or brought by us, may be necessary to determine the inventorship, priority, patentability or validity of inventions with respect to our patents or patent applications. An unfavorable outcome could leave our technology or product candidates without patent protection, allow third parties to commercialize our technology or product

candidates and compete directly with us, without payment to us, or could require us to obtain license rights from the prevailing party in order to be able to manufacture or commercialize our product candidates without infringing third-party patent rights. Our business could be harmed if the prevailing party in such a case does not offer us a license on commercially reasonable terms, or at all. Even if we obtain a license, it may be non-exclusive, thereby giving our competitors access to the same technologies licensed to us. In addition, if the breadth or strength of protection provided by our patents and patent applications is threatened, it could dissuade companies from collaborating with us to license, develop or commercialize current or future product candidates. Even if we successfully defend such litigation or proceeding, we may incur substantial costs and our defense may distract our management and other employees.

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. In addition, many foreign jurisdictions have rules of discovery that are different than those in the United States and that may make defending or enforcing our patents extremely difficult. 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 shares of our common stock.

Third parties may initiate legal proceedings against us alleging that we infringe their intellectual property rights or we may initiate legal proceedings against third parties to challenge the validity or scope of intellectual property rights controlled by third parties, including in oppositions, interferences, revocations, reexaminations, interpartes review or derivation proceedings before the USPTO or its counterparts in other jurisdictions. These proceedings can be expensive and time-consuming and many of our adversaries in these proceedings may have the ability to dedicate substantially greater resources to prosecuting these legal actions than we can. We could be found liable for monetary damages, including treble damages and attorneys’ fees, if we are found to have willfully infringed a patent of a third party. A finding of infringement could prevent us from commercializing our ~~BIO89-100~~pegozafermin or any future product candidates or force us to cease some of our business operations, which could materially harm our business.

Although we have reviewed certain third-party patents and patent filings that we believe may be relevant to our therapeutic candidates or products, we have not conducted a freedom-to-operate search or analysis for any of our therapeutic candidates or products, and we may not be aware of patents or pending or future patent applications that, if issued, would block us from commercializing our product candidates. Thus, we cannot guarantee that our product candidates, or our commercialization thereof, do not and will not infringe any third party’s intellectual property.

Thepriceof our common stock may be volatile,andyou may lose all or part of your investment.

The market price of our common stock could fluctuate significantly, and you may not be able to resell your shares at or above the price you paid for your shares. Those fluctuations could be based on various factors in addition to those otherwise described in this prospectus, including those described in these “Risk Factors.” Any of these factors may result in large and sudden changes in the volume and trading price of our common stock. In the past, following periods of volatility in the market price of a company’s securities, stockholders have often instituted securities class action litigation against that company.

Sales of our common stock, or the perception that such sales may occur, could depress the price of our common stock.

Sales of a substantial number of shares of our common stock in the public market, or the perception that such sales may occur, could depress the market price of our common stock. Certain holders of shares of our common stock have rights, subject to certain conditions, to require us to file registration statements covering their shares or to include their shares in registration statements that we may file for ourselves or other stockholders. In addition, we have filed a registration statement registering under the Securities Act the shares of our common stock reserved for issuance under our 2019 Equity Incentive Plan, including shares issuable upon exercise of outstanding options. These shares can be freely sold in the public market upon issuance, subject to volume limitations applicable to affiliates. Further, as opportunities present themselves, we may enter into financing or similar arrangements in the future, including the issuance of debt or equity securities.

Raising additionalcapitalmay cause dilutionto existing stockholders,restrictour operationsor requireus to relinquishrightsto our technologies.

Existing stockholders could suffer dilution or be negatively affected by fixed payment obligations we may incur if we raise additional funds through the issuance of additional equity securities, including under the ATM Facility, or debt or pursuant to the 2021 Loan Agreement. Furthermore, these securities may have rights senior to those of our common stock and could contain covenants or protective rights that would restrict our operations and potentially impair our competitiveness, such as limitations on our ability to incur additional debt, 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.

Ourdirectors,executiveofficersandcurrent holders of 5% or more of our capitalstock have substantialcontrolover our company,whichcould limityour abilityto influencethe outcomeof matterssubjectto stockholderapproval, including a change of control.

As of March 31, ~~2021,~~2022, our executive officers, directors and other holders of 5% or more of our common stock beneficially owned a majority of our outstanding common stock. As a result, our executive officers, directors and other holders of 5% or more of our common stock, if they act, will be able to influence or control matters requiring approval by our stockholders, including the election of directors and the approval of mergers, acquisitions or other extraordinary transactions. In addition, our current directors, executive officers and other holders of 5% or more of our common stock, acting together, would have the ability to control the management and affairs of our company. They may also have interests that differ from yours and may vote in a way with which you disagree and that may be adverse to your interests. This concentration of ownership may have the effect of delaying, preventing or deterring a change of control of our company, could deprive our stockholders of an opportunity to receive a premium for their shares of our common stock as part of a sale of our company.

We previously identifiedmaterialweaknesses in our internalcontrolover financialreporting, which have been remediated. If we identify additional material weaknesses in the future or otherwise fail to maintainaneffectivesystemof internalcontrols, wemay not be able to produce timely and accurate financialstatements, and we or our independent registered public accounting firm may conclude that our internal control over financial reporting is not effective,whichcould adverselyaffect our investors’confidence and our stock price.

As an emerging growth company under the JOBS Act, our management is required to report upon the effectiveness of our internal control over financial reporting under Section 404 of the Sarbanes-Oxley Act. Our independent registered public accounting firm is not required to formally attest to the effectiveness of our internal control over financial reporting until the date we are no longer an emerging growth company and reach accelerated filer status. Any failure to implement required new or improved controls, or difficulties encountered in their implementation, could cause us to fail to meet our reporting obligations. In addition, any testing by us conducted in connection with Section 404, or any subsequent testing by our independent registered public accounting firm, may reveal deficiencies in our internal controls over financial reporting that are deemed to be material weaknesses or that may require prospective or retroactive changes to our consolidated financial statements or identify other areas for further attention or improvement. As previously disclosed, in connection with our financial statement close process for 2018, we identified material weaknesses in the design and operating effectiveness of our internal control over financial reporting. While we have remediated such material weaknesses, we cannot assure you that we have identified all material weaknesses or that there will not be additional material weaknesses or deficiencies that we will identify in the future.

Our amended and restated certificate of incorporation, amended and restated bylaws and Delaware law could prevent a third party from acquiring us (even if an acquisition would benefit our stockholders), may limit the ability of our stockholders to replace our management and limit the price that investors might be willing to pay for shares of our common stock.

Our amended and restated certificate of incorporationand our amended and restated bylaws could have the effectof makingit moredifficultfor a thirdpartyto acquire,or of discouraginga thirdpartyfromattemptingto acquire,controlof us. These provisionscould delay or preventa change in controlof the company and could limitthe pricethatinvestors mightbe willingto pay in the futurefor sharesof our commonstock. In addition, asa Delaware corporation,weare subjectto the anti-takeoverprovisionsof Section203 of the Delaware GeneralCorporationLaw,which prohibitsa Delaware corporationfromengaging in a business combinationspecifiedin the statutewith an interestedstockholder ~~(as~~(as definedin the statute)for a periodof three yearsafterthe date of the transactionin which the person firstbecomesan interestedstockholder,unlessthe businesscombinationis approved in advance by a majorityof the independentdirectorsor by the holdersof at leasttwo-thirdsof the outstandingdisinterestedshares.The applicationof Section203 of the Delaware General CorporationLawcould also have the effectof delayingor preventinga change of controlof us.

Our amended and restated certificate of incorporation provides that the Court of Chancery of the State of Delaware and the federal district courts of the United States 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 or employees.

Our amended and restated certificate of incorporation provides that the Court of Chancery of the State of Delaware is the exclusive forum for certain actions or proceedings under Delaware statutory or common law. Our amended and restated certificate of incorporation provides further that the federal district courts of the United States will be the exclusive forum for resolving any complaint asserting a cause of action arising under the Securities Act. These choice of forum provisions 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 or other employees. If a court were to find the choice of forum provision contained in our amended and restated certificate of incorporation to be inapplicable or unenforceable, we may incur additional costs associated with resolving such action in other jurisdictions.

On November 13, 2019, we completed our initial public offering (“IPO”), pursuant to which we issued and sold an aggregate of 6,100,390 shares of common stock at the IPO price of $16.00 per share. The aggregate gross proceeds from our IPO were $97.6 million, and the net proceeds were $87.7 million after deducting underwriting discounts and commissions of $6.8 million and other offering expenses of $3.1 million. The offer and sale of the shares of common stock in the IPO were registered pursuant to registration statements on Form S-1 (File Nos. 333-234174 and 333-234617), which the SEC declared effective on November 8, 2019. No offering expenses were paid directly or indirectly to any of our directors or officers (or their associates) or persons owning 10% or more of any class of our equity securities or to any other affiliates. The underwriters for our IPO were BofA Securities, Inc., SVB Leerink LLC, RBC Capital Markets, LLC, and Oppenheimer & Co. Inc.

The net proceeds from our IPO have been used and will be used, together with our cash and cash equivalents to complete our ongoing POC Phase 1b/2a clinical trial and initiate our subsequent Phase 2b clinical trial of BIO89-100 in patients with NASH, fund our Phase 2 trial of BIO89-100 in patients with SHTG as well as evaluate potential new indications for BIO89-100, and BIO89-100 manufacturing and scale up, with the balance to be used to fund working capital and other general corporate purposes, which may include licensing, acquiring or investing in complementary businesses, technologies, products or assets, the acquisition or licensing of other products, businesses or technologies.

~~There has been no material change in the intended use of proceeds from our IPO as described in our final prospectus filed with the SEC pursuant to Rule 424(b)(4) on November 12, 2019.~~

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.

Delaware	36-4946844
(State or other jurisdiction of incorporation or organization)	(I.R.S. Employer Identification No.)
142 Sansome Street, Second Floor San Francisco, California 94104	94104
(Address of principal executive offices)	(Zip Code)

		Page
PART I.	FINANCIAL INFORMATION
Item 1.	Financial Statements (Unaudited)	1
	Condensed Consolidated Balance Sheets	1
	Condensed Consolidated Statements of Operations and Comprehensive Loss	2
	Condensed Consolidated Statements of ~~Stockholder’s~~Stockholders’ Equity	3
	Condensed Consolidated Statements of Cash Flows	4
	Notes to Unaudited Condensed Consolidated Financial Statements	5
Item 2.	Management’s Discussion and Analysis of Financial Condition and Results of Operations	1213
Item 3.	Quantitative and Qualitative Disclosures About Market Risk	1718
Item 4.	Controls and Procedures	18
PART II.	OTHER INFORMATION	20
Item 1.	Legal Proceedings	1920
Item 1A.	Risk Factors	1920
Item 2.	Unregistered Sales of Equity Securities and Use of Proceeds	3536
Item 3.	Default Upon Senior Securities	36
Item 4.	Mine Safety Disclosures	36
Item 5.	Other Information	36
Item 6.	Exhibits	37
Signatures		38

	March 31,		December 31,
	2022		2021
Prepaid research and development	$	6,201	$	7,895
Prepaid taxes		831		836
Prepaid other		2,266		2,506
Total prepaid and other current assets	$	9,298	$	11,237

Remainder of 2022	$	2,500
2023		10,000
2024		7,500
Total principal repayments		20,000
Less: unamortized debt discount		(527	)
Total term loan, net		19,473
Less: term loan, current		(5,000	)
Term loan, non-current, net	$	14,473

				Weighted Average
	Number of			Grant Date
	RSUs			Fair Value

Balance outstanding as of December 31, 2021		106,394		$	23.10
Granted		596,891			4.44
Vested / Released		(22,115	)		23.10
Cancelled / Forfeited		(49,105	)		5.31
Balance outstanding as of March 31, 2022		632,065		$	6.48

	March 31, 2021
Remainder of 2021	$	166
2022		8
Total future minimum annual payments	$	174

Exhibit Number		Description

2.1		Contribution and Exchange Agreement, dated as of September 17, 2019, by and among 89Bio Ltd., the Company and its shareholders (filed with the SEC as Exhibit 2.1 to the Company’s Form S-1 filed on October 11, 2019).

3.1		Second Amended and Restated Certificate of Incorporation (filed with the SEC as Exhibit 3.1 to the Company’s Form 8-K filed on November 15, 2019).

3.2		Second Amended and Restated Bylaws (filed with the SEC as Exhibit 3.2 to the Company’s Form 8-K filed on November 15, 2019).

4.1		Specimen common stock certificate of the registrant (filed with the SEC as Exhibit 4.1 to the Company’s Form S-1/A filed on October 28, 2019).

4.2		Investors’ Rights Agreement, dated as of September 17, 2019, by and among the Company and certain of its shareholders (filed with the SEC as Exhibit 4.2 to the Company’s Form S-1 filed on October 11, 2019).

4.3		Form of Warrant to Purchase Common Stock for Silicon Valley Bank (filed with SEC as Exhibit 4.1 to the Company’s Form 8-K filed on April 13, 2020).

10.131.1		~~First Amendment to Loan and Security Agreement, dated as of March 30, 2021, among Silicon Valley Bank, the Lenders party thereto, 89bio, Inc., 89bio Management, Inc. and 89Bio Ltd.~~

10.2*		~~Second Amendment to Loan and Security Agreement, dated as of April 30, 2021, among Silicon Valley Bank, the Lenders party thereto, 89bio, Inc., 89bio Management, Inc. and 89bio Ltd.~~

31.1*		Certification of Principal Executive Officer Pursuant to Rules 13a-14(a) and 15d-14(a) under the Securities Exchange Act of 1934.

31.2*		Certification of Principal Financial Officer Pursuant to Rules 13a-14(a) and 15d-14(a) under the Securities Exchange Act of 1934.

32#		Certification of Principal Executive Officer and Principal Financial Officer Pursuant to 18 U.S.C. Section 1350.

101.INS*		Inline XBRL Instance Document

101.SCH*		Inline XBRL Taxonomy Extension Schema Document

101.CAL*		Inline XBRL Taxonomy Extension Calculation Linkbase Document

101.DEF*		Inline XBRL Taxonomy Extension Definition Linkbase Document

101.LAB*		Inline XBRL Taxonomy Extension Label Linkbase Document

101.PRE*		Inline XBRL Taxonomy Extension Presentation Linkbase Document

104		The cover page for the Company’s Quarterly Report on Form 10-Q has been formatted in Inline XBRL and contained in Exhibit 101

	89bio, Inc.

Date: May 13~~, 2021~~12, 2022	By:	/s/ Rohan Palekar
		Rohan Palekar
		Chief Executive Officer (principal executive officer)

Date: May ~~13, 2021~~12, 2022	By:	/s/ Ryan Martins
		Ryan Martins Chief Financial Officer
		(principal financial and accounting officer)

Large accelerated filer

Accelerated filer

Non-accelerated filer

Smaller reporting company

Emerging growth company