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UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

~~Washington,~~WASHINGTON, D.C. 20549

FORM 10-Q

(M~~ark One)~~



(Mark One)
ý		QUARTERLY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
For the quarterly period ended March 31, 2019
Or
o		TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
For the transition period from to

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

~~For the quarterly period ended September 30, 2017~~

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

Commission file number: 001-36080

IVERIC bio, Inc.

~~Ophthotech Corporation~~

(Exact name of registrant as specified in its charter)



~~Delaware~~		~~20-8185347~~
Delaware (State or other jurisdiction of incorporation or organization)		20-8185347 (I.R.S. Employer Identification ~~Number)~~No.)

One Penn Plaza, ~~19th~~35th Floor New York, NY		~~10119~~
(Address of principal executive offices)		10119 (Zip Code)

(212) 845-8200

(~~Registrant’s~~Registrant's telephone number, including area code)

Ophthotech Corporation

(Former name, former address and former fiscal year, if changed since last report)

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. ýYes xo No¨

Indicate by check mark whether the registrant has submitted electronically ~~and posted on its corporate Web site, if any,~~ every Interactive Data File required to be submitted ~~and posted~~ 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 ~~and post~~ such files). ýYes xo No¨

Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, a 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.



Large accelerated filer x¨	Accelerated filer ¨x	Non-accelerated filer ¨	Smaller reporting company ¨x	Emerging growth company ¨
~~(Do not check if a smaller reporting company)~~

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

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

AsSecurities registered pursuant to Section 12(b) of ~~November 6, 2017 there were 36,038,683 shares of Common Stock, $0.001 par value per share, outstanding.~~the Act:

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Title of each class	Trading Symbol(s)	Name of each exchange on which registered
Common Stock, $0.001 par value per share	ISEE	The Nasdaq Global Select Market

As of May 6, 2019 there were 41,477,420 shares of Common Stock, $0.001 par value per share, outstanding.

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FORWARD-LOOKING STATEMENTS

This Quarterly Report on Form 10-Q contains forward-looking statements that involve substantial risks and uncertainties. All statements, other than statements of historical facts, contained in this Quarterly Report on Form 10-Q, including statements regarding our strategy, future operations, future financial position, future revenues, projected costs, prospects, plans and objectives of management, are forward-looking statements. The words “anticipate,” “believe,” “goals,” “estimate,” “expect,” “intend,” “may,” “might,” “plan,” “predict,” “project,” “target,” “potential,” “will,” “would,” “could,” “should,” “continue”"anticipate," "believe," "goals," "estimate," "expect," "intend," "may," "might," "plan," "predict," "project," "target," "potential," "will," "would," "could," "should," "continue" and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words.

The forward-looking statements in this Quarterly Report on Form 10-Q include, among other things, statements about:

the potential benefits of our ~~updated~~ business plan and strategy to ~~continue~~develop IC-100, our gene therapy product candidate for rhodopsin-mediated autosomal dominant retinitis pigmentosa, and IC-200, our gene therapy product candidate for Best vitelliform macular dystrophy and other bestrophinopathies, to develop Zimura® (avacincaptad pegol) in geographic atrophy secondary to dry age-related macular degeneration and autosomal recessive Stargardt disease, to progress the development ~~programs, initiate new development programs~~of our HtrA1 inhibitor program in geographic atrophy secondary to dry age-related macular degeneration, and to potentially further expand our product ~~pipeline;~~

pipeline, including through our ability to in-license or acquire additional products, product candidates or technologies to treat ophthalmic diseases and the timing, costs, conduct and outcome of preclinical development or clinical trials we undertake for these newly acquired assets;collaborative gene therapy sponsored research programs;

our expectations related to our use of available cash;

our estimates regarding expenses, future revenues, capital requirements and needs for, and ability to obtain, additional financing;

the timing, costs, conduct and outcome of our clinical trial of Zimura as a monotherapy for the treatment of geographic atrophy, or GA, secondary to dry AMD, our clinical trial of Zimura in combination with an anti-VEGF drug for the treatment of wet AMD, ourongoing and planned clinical trial of Zimura as a monotherapy for autosomal recessive Stargardt disease, which we refer to as STGD1, our planned clinical trial of Zimura in combination with an anti-VEGF drug for the treatment of idiopathic polypoidal choroidal vasculopathy,research and ~~our planned clinical trial of Zimura as a monotherapy for non-infectious intermediate and posterior uveitis,~~preclinical development activities, including statements regarding the timing of the initiation of and completion of ~~enrollment in~~these activities, and the costs to obtain and timing of receipt of results from, and the completion of, such activities;

the timing, costs, conduct and outcome of our ongoing clinical trials, including statements regarding the timing of the completion of such trials, and the costs to obtain and timing of receipt of initial results from, and the completion of, such trials;

our ability to establish and maintain arrangements for the manufacture of our product candidates;

the timing of and our ability to obtain marketing approval of our product candidates, and the ability of our product candidates to meet existing or future regulatory standards;

our ability to in-license or acquire additional product candidates or technologies to treat retinal diseases and the timing, costs, conduct and outcome of research and preclinical development or clinical trials we undertake for these newly in-licensed or acquired assets;

the potential advantages of our product candidates and other technologies that we are pursuing, including the advantages and limitations of gene therapy, including use of "minigenes", inhibition of the complement system and HtrA1, and other mechanisms of action in which we are pursuing development of our product candidates;

our estimates regarding the potential market opportunity for our product candidates;

our sales, marketing and distribution capabilities and strategy;

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

~~our estimates regarding the potential market opportunity for our product candidates;~~

the potential receipt of revenues from future sales of our product candidates, if approved;

~~our sales, marketing and distribution capabilities and strategy;~~

~~our ability to establish and maintain arrangements for the manufacture of our product candidates;~~

our intellectual property position;

the impact of existing and new governmental laws and regulations; and

our competitive position.

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We may not actually achieve the plans, intentions or expectations disclosed in our forward-looking statements, and our stockholders should not place undue reliance on our forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in the forward-looking statements we make. We have included important factors in the cautionary statements included in this Quarterly Report on Form 10-Q, particularly in the ~~“Risk Factors”~~"Risk Factors" section, that could cause actual results or events to differ materially from the forward-looking statements that we make. Our ~~forward-~~

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~~looking~~forward-looking statements do not reflect the potential impact of any future acquisitions, mergers, licenses, dispositions, joint ventures or investments we may make.

You should read this Quarterly Report on Form 10-Q and the documents that we have filed as exhibits to this Quarterly Report on Form 10-Q and our other periodic reports, completely and with the understanding that our actual future results may be materially different from what we expect. The forward-looking statements contained in this Quarterly Report on Form 10-Q are made as of the date of this Quarterly Report on Form 10-Q, and we do not assume any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by applicable law.

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PART I—FINANCIAL INFORMATION

Item 1. Financial Statements

~~OPHTHOTECH CORPORATION~~IVERIC bio, Inc.

Unaudited Consolidated Balance Sheets

(in thousands, except share and per share data)


	September 30, 2017			December 31, 2016
							March 31, 2019			December 31, 2018
Assets
Current assets
Cash and cash equivalents	$	180,217		$	133,930		$	116,639		$	131,201
Available for sale securities	—			155,348
Due from Novartis Pharma AG	—			3,531
Prepaid expenses and other current assets	1,436			3,078			2,395			2,086
Total current assets	181,653			295,887			119,034			133,287
Property and equipment, net	1,302			3,281			292			335
Right-of-use asset, net							1,230			—
Income tax receivable, non-current							3,529			3,529
Other assets	27			462			11			14
Total assets	$	182,982		$	299,630		$	124,096		$	137,165
Liabilities and Stockholders’ Equity (Deficit)
Liabilities and Stockholders' Equity
Current liabilities
Accrued research and development expenses	$	6,212		$	47,240		$	5,910		$	7,337
Accounts payable and accrued expenses	7,895			12,032			2,987			5,869
Deferred revenue	—			6,646
Lease liability							985			—
Total current liabilities	14,107			65,918			9,882			13,206
Deferred revenue, long-term	—			203,330
Royalty purchase liability	125,000			125,000
Lease liability, non-current							245			—
Total liabilities	139,107			394,248			10,127			13,206
Stockholders’ equity (deficit)
Preferred stock - $0.001 par value, 5,000,000 shares authorized, no shares issued or outstanding	$	—		$	—
Common stock - $0.001 par value, 200,000,000 shares authorized, 36,032,883 and 35,733,276 shares issued and outstanding at September 30, 2017 and December 31, 2016, respectively	36			36
Stockholders' equity
Preferred stock—$0.001 par value, 5,000,000 shares authorized, no shares issued or outstanding							$	—		$	—
Common stock—$0.001 par value, 200,000,000 shares authorized, 41,453,070 and 41,397,197 shares issued and outstanding at March 31, 2019 and December 31, 2018, respectively							41			41
Additional paid-in capital	519,051			504,517			548,096			545,585
Accumulated deficit	(475,212		)	(598,959		)	(434,168		)	(421,667		)
Accumulated other comprehensive loss	—			(212		)
Total stockholders’ equity (deficit)	43,875			(94,618		)
Total liabilities and stockholders’ equity (deficit)	$	182,982		$	299,630
Total stockholders' equity							113,969			123,959
Total liabilities and stockholders' equity							$	124,096		$	137,165

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

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IVERIC bio, Inc.

Unaudited Consolidated Statements of Operations and Comprehensive Loss

(in thousands, except per share data)



	Three Months Ended March 31,
	2019			2018
Operating expenses:
Research and development	$	7,685		$	7,686
General and administrative	5,481			5,645
Total operating expenses	13,166			13,331
Loss from operations	(13,166		)	(13,331		)
Interest income	670			473
Other expense	—			(16		)
Loss before income tax provision	(12,496		)	(12,874		)
Income tax provision	5			199
Net loss	$	(12,501	)	$	(13,073	)
Comprehensive loss	$	(12,501	)	$	(13,073	)
Net loss per common share:
Basic and diluted	$	(0.30	)	$	(0.36	)
Weighted average common shares outstanding:
Basic and diluted	41,427			36,153

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

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~~OPHTHOTECH CORPORATION~~IVERIC bio, Inc.

Unaudited Consolidated Statements of ~~Operations~~Stockholders' Equity

(in ~~thousands, except per share data)~~thousands)

Three Months Ended September 30, Nine Months Ended September 30,
2017 2016 2017 2016

Collaboration revenue $ 206,654
$ 1,668
$ 209,977
$ 45,587
Operating expenses:

Research and development 10,707
50,854
58,343
136,886
General and administrative 7,059
12,024
28,770
37,209
Total operating expenses 17,766
62,878
87,113
174,095
Income (loss) from operations 188,888
(61,210 ) 122,864
(128,508 )
Interest income 391
409
1,113
1,301
Other loss (12 ) (20 ) (34 ) (88 )
Income (loss) before income tax provision (benefit) 189,267
(60,821 ) 123,943
(127,295 )
Income tax provision (benefit) 194
70
196
(158 )
Net income (loss) $ 189,073
$ (60,891 ) $ 123,747
$ (127,137 )
Net income (loss) per common share:

Basic $ 5.26
$ (1.71 ) $ 3.45
$ (3.59 )
Diluted $ 5.25
$ (1.71 ) $ 3.44
$ (3.59 )
Weighted average common shares outstanding:

Basic 35,971
35,594
35,878
35,415
Diluted 36,047
35,594
35,984
35,415



	Preferred Stock			Common Stock			Additional paid-in capital		Accumulated Deficit			Total
	Shares	Amount		Shares	Amount		Additional paid-in capital		Accumulated Deficit			Total
Balance at December 31, 2018	—	$	—	41,397	$	41	$	545,585	$	(421,667	)	$	123,959
Issuance of common stock under employee stock compensation plans	—	—		56	—		41		—			41
Share-based compensation	—	—		—	—		2,470		—			2,470
Net loss	—	—		—	—		—		(12,501		)	(12,501		)
Balance at March 31, 2019	—	$	—	41,453	$	41	$	548,096	$	(434,168	)	$	113,969

Balance at December 31, 2017	—	$	—	36,110	$	36	$	522,759	$	(484,754	)	$	38,041
Issuance of common stock under employee stock compensation plans	—	—		54	—		27		—			27
Share-based compensation	—	—		—	—		3,082		—			3,082
Net loss	—	—		—	—		—		(13,073		)	(13,073		)
Balance at March 31, 2018	—	$	—	36,164	$	36	$	525,868	$	(497,827	)	$	28,077

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

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~~OPHTHOTECH CORPORATION~~IVERIC bio, Inc.

Unaudited Consolidated Statements of ~~Comprehensive Income (Loss)~~Cash Flows

(in thousands)

Three Months Ended September 30, Nine Months Ended September 30,
2017 2016 2017 2016

Net income (loss) $ 189,073
$ (60,891 ) $ 123,747
$ (127,137 )
Other comprehensive income (loss):

Unrealized gain (loss) on available for sale securities, net of tax 186
(41 ) 212
314
Other comprehensive income (loss) 186
(41 ) 212
314
Comprehensive income (loss) $ 189,259
$ (60,932 ) $ 123,959
$ (126,823 )



	Three Months Ended March 31,
	2019			2018
Operating Activities
Net loss	(12,501		)	$	(13,073	)
Adjustments to reconcile net loss to net cash used in operating activities
Depreciation and other expense	43			50
Deferred income taxes	—			233
Share-based compensation	2,470			3,082
Changes in operating assets and liabilities:
Income tax receivable	—			1,387
Prepaid expense and other current assets	(309		)	310
Other assets	3			(16		)
Accrued research and development expenses	(1,427		)	212
Accounts payable and accrued expenses	(2,882		)	(4,273		)
Net cash used in operating activities	(14,603		)	(12,088		)
Investing Activities
Net cash provided by (used in) investing activities	—			—
Financing Activities
Proceeds from employee stock plan purchases	41			27
Net cash provided by financing activities	41			27
Net change in cash and cash equivalents	(14,562		)	(12,061		)
Cash and cash equivalents
Beginning of period	131,201			166,972
End of period	$	116,639		$	154,911
Supplemental disclosure of cash paid
Income tax refunds received	$	—		$	(1,425	)

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

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~~OPHTHOTECH CORPORATION~~

~~Unaudited Statements of Cash Flows~~

~~(in thousands)~~

Nine Months Ended September 30,
2017 2016

Operating Activities

Net income (loss) $ 123,747
$ (127,137 )
Adjustments to reconcile net income (loss) to net cash used in operating activities

Depreciation 1,979
539
Amortization of premium and discounts on investment securities 140
454
Deferred income taxes 163
22,916
Share-based compensation 14,463
24,889
Changes in operating assets and liabilities:

Due from Novartis Pharma AG 3,531
4,383
Income tax receivable (52 ) (20,844 )
Prepaid expense and other current assets 1,694
569
Accrued interest receivable 465
157
Other assets 435
19
Accrued research and development expenses (41,028 ) 21,197
Accounts payable and accrued expenses (4,137 ) (1,629 )
Deferred revenue (209,976 ) (1,298 )
Net cash used in operating activities (108,576 ) (75,785 )
Investing Activities

Purchase of marketable securities (12,014 ) (48,123 )
Maturities of marketable securities 166,806
62,500
Purchase of property and equipment —
(247 )
Net cash provided by investing activities 154,792
14,130
Financing Activities

Proceeds from stock option/employee stock purchase plan exercises 71
5,398
Net cash provided by financing activities 71
5,398
Net change in cash and cash equivalents 46,287
(56,257 )
Cash and cash equivalents

Beginning of period 133,930
221,861
End of period $ 180,217
$ 165,604
Supplemental disclosures of non-cash information related to investing activities

Change in unrealized gain (loss) on available for sale securities, net of tax $ 212
$ 314

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

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~~OPHTHOTECH CORPORATION~~IVERIC bio, Inc.

Notes to Unaudited Consolidated Financial Statements

(~~tabular dollars and shares~~ in thousands, except per share data)

1. Business

Description of Business and Organization

IVERIC bio, Inc. (the “Company”), formerly Ophthotech Corporation, ~~(the “Company” or “Ophthotech”)~~ was incorporated on January 5, 2007, in Delaware. The Company is a science-driven biopharmaceutical company ~~specializing in the development of novel therapeutics to treat ophthalmic diseases,~~ with a focus on ~~age-related~~discovering and developing novel gene therapy solutions to treat orphan inherited retinal diseases ("IRDs") with unmet medical needs. The Company recently changed its name from Ophthotech Corporation to IVERIC bio, Inc. to reflect the transition of its business to focus principally on gene therapies. The Company believes that gene therapy as a treatment modality, especially gene therapies using adeno-associated virus ("AAV") for gene delivery, holds tremendous promise for retinal diseases. The Company ~~currently has two product candidates in development,~~also continues to develop its therapeutic programs, including its ongoing clinical trials for its C5 complement inhibitor Zimura® (avacincaptad pegol), for an ~~anti-complement factor C5 aptamer,~~age-related retinal disease and ~~Fovista® (pegpleranib),~~for an ~~anti-platelet derived growth factor, or PDGF, aptamer. Prior to 2017,~~orphan IRD.

The Company's gene therapy portfolio consists of several ongoing research and preclinical development programs that use AAV for gene delivery. These AAV gene therapy programs are targeting the ~~Company's primary focus was on developing Fovista and Zimura for various types of age-related macular degeneration, or AMD,~~following orphan IRDs:

rhodopsin-mediated autosomal dominant retinitis pigmentosa ("RHO-adRP"), which is ~~a disorder~~characterized by progressive and severe bilateral loss of vision leading to blindness;

Best vitelliform macular dystrophy ("Best disease"), which is characterized by bilateral egg yolk-like lesions in the central portion of the retina ~~known as~~(the "macula") that, over time, progress to atrophy and loss of vision, and potentially other diseases associated with mutations in the Best1 gene ("bestrophinopathies");

Leber congenital amaurosis type 10 ("LCA10"), which is characterized by severe bilateral loss of vision at or soon after birth; and

autosomal recessive Stargardt disease, which is characterized by progressive damage to the macula ~~that~~and retina, leading to loss of vision in children and young adults.

The Company's therapeutics portfolio consists of Zimura and its program of High temperature requirement A serine peptidase 1 protein ("HtrA1") inhibitors. The Company has Phase 2b clinical trials ongoing evaluating Zimura for the treatment of:

geographic atrophy ("GA"), which is a late-stage form of dry age-related macular degeneration ("AMD") characterized by retinal cell death and degeneration of tissue in the macula, and which may result in ~~blindness. In December 2016, the~~loss of vision; and

autosomal recessive Stargardt disease.

The Company ~~announced that two of its three pivotal Phase 3 clinical trials for Fovista~~previously also evaluated Zimura in combination with ~~the~~Lucentis® (ranibizumab), an anti-vascular endothelial growth factor ~~or anti-VEGF, drug Lucentis® (ranibizumab)~~("anti-VEGF") agent, for the treatment of wet AMD, ~~failed~~for which it completed a Phase 2a clinical trial during the fourth quarter of 2018. The Company does not currently have plans to ~~meet their primary endpoint. In August 2017,~~develop Zimura further in wet AMD. The Company's HtrA1 inhibitor program, which it is developing for GA secondary to dry AMD and potentially other age-related retinal diseases, is in the preclinical stage of development.

The Company's business development efforts have resulted in the expansion of its research and development pipeline and the transition of the Company ~~announced that the third pivotal Phase 3 clinical trial for Fovista in combination~~to focus principally on gene therapy. The Company initiated its gene therapy sponsored research programs with the ~~anti-VEGF drugs Eylea® (aflibercept) or Avastin® (bevacizumab)~~University of Massachusetts Medical School ("UMMS") in February 2018, in-licensed its novel AAV gene therapy product candidate for the treatment of ~~wet AMD, referred to as~~RHO-adRP ("IC-100") from the ~~OPH1004 trial, failed to meet~~University of Florida Research Foundation ("UFRF") and the University of Pennsylvania ("Penn") in June 2018 and in-licensed its primary endpoint. The Company is in the process of winding down the OPH1004 Fovista trial and has no future plans to develop Fovista in wet AMD and only very limited Fovista development activity outside of wet AMD. In early 2017, the Company announced that it had engaged a financial advisor to assist it in reviewing the Company’s strategic alternatives, including identifying potential business development opportunities. Also beginning in early 2017, the Company undertook a reassessment of its development plans for Zimura and Fovista, which included an evaluation of the scientific rationale for potentially developing thesenovel AAV gene therapy product candidates in one or more other ophthalmic indications for which there is a high unmet need. In July 2017, the Company announced that it is pursuing a strategy to leverage its clinical experience and retina expertise to identify and develop therapies to treat multiple ophthalmic orphan diseases for which there are limited or no treatment options available. To this end, the Company is preparing to initiate a randomized, controlled Phase 2b clinical trial of Zimura as a monotherapycandidate for the treatment of ~~autosomal recessive Stargardt~~Best disease and other bestrophinopathies ("~~STGD1"~~IC-200")~~, an inherited retinal orphan disease causing vision loss during childhood or adolescence, before the end~~ from Penn and UFRF in April 2019 (See "Note 10—Subsequent Event" for a description of ~~2017. In parallel, the Company is continuing its on-going Zimura programs in age-related retinal diseases.~~this in-license transaction). The Company is also ~~continuing~~acquired its business development efforts to identify and potentially obtain rights to additional products, product candidates and technologies that would complement its strategic goals as well as other compelling ophthalmology opportunities.HtrA1 inhibitor program through the acquisition of Inception 4, Inc. ("Inception 4") in October 2018.

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2. Summary of Significant Accounting Policies

The Company’s significant accounting policies are described in Note 2, ~~“Significant~~“Summary of Significant Accounting Policies,” in the notes to the audited consolidated financial statements included in the Company’s Annual Report on Form 10-K for the year ended December 31, ~~2016.~~

~~Basis of Presentation~~

The accompanying unaudited financial information as of September 30, 2017 and for the three and nine months ended September 30, 2017 and 2016 has been prepared by the Company pursuant to the rules and regulations of2018 filed with the Securities and Exchange Commission ~~(“SEC”~~("SEC")~~. Certain information and footnote disclosures normally included in~~ on February 28, 2019.

Basis of Presentation

The accompanying financial statements have been prepared in accordance with ~~U.S.~~accounting principles generally accepted ~~accounting principles (“GAAP”~~in the United States ("GAAP") and include all adjustments necessary for the fair presentation of the Company's financial position for the periods presented. The consolidated financial statements include the accounts of the Company and its subsidiaries. All intercompany balances and transactions have been condensed or omitted pursuant to such rules and regulations. The December 31, 2016 Balance Sheet was derived from the Company’s audited financial statements. These interim financial statements should be readeliminated in ~~conjunction with the notes to the financial statements contained in the Company’s Annual Report on Form 10-K (“Annual Report”) for 2016, as filed with the SEC on February 28, 2017.~~

In the opinion of management, the unaudited financial information as of September 30, 2017 and for the three and nine months ended September 30, 2017 and 2016, reflects all adjustments, which are normal recurring adjustments, necessary to present a fair statement of the financial position, results of operations and cash flows of the Company. The results of operations for the three and nine months ended September 30, 2017 and 2016 are not necessarily indicative of the operating results for the full fiscal year or any future period.

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consolidation.

Segment and geographic information

Operating segments are defined as components of an enterprise about which separate discrete information is available for evaluation by the chief operating decision maker, or ~~decision making~~decision-making group, in deciding how to allocate resources and in assessing performance. The Company views its operations and manages its business in one operating and reporting segment.

Use of Estimates

The preparation of financial statements and related disclosures in conformity with GAAP requires management to make estimates and judgments that affect the amounts reported in the financial statements and accompanying notes. The Company bases its estimates and judgments on historical experience and on various other assumptions that it believes are reasonable under the circumstances. The amounts of assets and liabilities reported in the ~~Company’s~~Company's Consolidated Balance Sheets and the amount of expenses reported for each of the periods presented are affected by estimates and assumptions, which are used for, but not limited to, accounting for research and development costs, revenue recognition, accounting for share-based compensation and accounting for income taxes. Actual results could differ from those estimates.

Cash and Cash Equivalents

The Company considers all highly liquid investments with an original maturity of 90 days or less when purchased to be cash equivalents. The carrying amounts reported in the Balance Sheets for cash and cash equivalents are valued at cost, which approximates their fair value.

As of ~~September 30, 2017,~~March 31, 2019, the Company had cash and cash equivalents of approximately ~~$180.2~~$116.6 million. The Company believes that its existing cash and cash equivalents as of September 30, 2017 will be sufficient to fund its operations and capital expenditure requirements as currently planned for at least the next 12 months.

~~Available for Sale Securities~~

The Company considers securities with original maturities of greater than 90 days when purchased to be available for sale securities. Available for sale securities with original maturities of greater than one year are recorded as non-current assets. Available for sale securities are recorded at fair value and unrealized gains and losses are recorded within accumulated other comprehensive income (loss). The estimated fair value of the available for sale securities is determined based on quoted market prices or rates for similar instruments. In addition, the cost of debt securities in this category is adjusted for amortization of premium and accretion of discount to maturity. The Company evaluates securities with unrealized losses to determine whether such losses, if any, are other than temporary.

~~Revenue Recognition~~

~~Collaboration Revenue~~

In May 2014, the Company received an upfront payment of $200.0 million in connection with its licensing and commercialization agreement (the “Novartis Agreement”) with Novartis Pharma AG ("Novartis"). Prior to the third quarter of 2017, this payment had not been recorded as revenue due to the existence of a contingency with respect to the Company's right to terminate the agreement in certain circumstances and the associated termination fee equivalent to the entire $200.0 million upfront payment, which the Company would have been required to pay if it had elected to exercise this termination option. The Company and Novartis entered into a letter agreement in July 2017 (the "Letter Agreement") that waived the Company's termination right, thereby resolving the contingency and allowing the Company to immediately recognize as revenue the portion of the upfront payment allocated using the relative selling price method to deliverables completed during prior periods. See "Note 5-Licensing and Commercialization Agreement with Novartis Pharma AG" below for a further description of the Letter Agreement. During the third quarter of 2017, the Company completed the remaining deliverables under the Novartis Agreement and the Letter Agreement and recognized as revenue the balance of all of the payments previously received from Novartis related to licensing, research and development, manufacturing and joint operating committee activities that had been previously deferred using the relative selling price method. In total, during the third quarter of 2017, the Company recognized $206.7 million in previously deferred collaboration revenue in connection with the Novartis Agreement. The recognition of this revenue during the period did not impact the Company's cash balance. On October 23, 2017, following the failure of the Phase 3 Fovista program and pursuant to the terms of the Letter Agreement, Novartis elected to terminate the Novartis Agreement with immediate effect.

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~~Below is a summary of the components of the Company’s collaboration revenue for the three and nine months ended September 30, 2017 and 2016:~~

Three months ended September 30, Nine months ended September 30,
2017 2016 2017 2016

License revenue $ 152,912
$ —
$ 152,912
$ 22,937
Research and development activity revenue 52,864
1,664
56,180
8,089
API transfer revenue 754
—
754
14,545
Joint operating committee revenue 124
4
131
16
Total collaboration revenue $ 206,654
$ 1,668
$ 209,977
$ 45,587

Concentration of Credit Risk

The ~~Company’s~~Company's financial instruments that are exposed to concentration of credit risk consist primarily of cash and cash ~~equivalents and available for sale securities.~~equivalents. The Company maintains its cash in bank accounts, the balances of which generally exceed federally insured limits. The Company maintains its cash equivalents in investments in money market funds and, at times, in U.S. Treasury securities and investment-grade corporate debt securities with original maturities of 90 days or less.

The Company’s available for sale securities are also invested in U.S. Treasury securities and investment-grade corporate debt securities. The Company believes it is not exposed to significant credit risk on its cash, cash equivalents and available for sale securities. As of September 30, 2017, the Company did not hold any available for sale securities.

Concentration of Suppliers

The Company currently relies exclusively upon a single third-party contract manufacturer for IC-100 and IC-200, and expects to rely on sole-source suppliers for certain starting materials to be used in the manufacture of such product candidates. The Company currently relies exclusively upon a single third-party manufacturer to provide supplies of the ~~active pharmaceutical ingredient, or API,~~drug substance for Zimura on a purchase order basis. The Company also engages a single third-party manufacturer to provide fill/finish services for clinical supplies of Zimura. In addition, the Company currently relies upon a single third-party supplier to supply it with the ~~proprietary~~ polyethylene glycol ~~or PEG,~~ reagent used to manufacture Zimura on a purchase order basis. Furthermore, the Company and its contract manufacturers currently rely upon sole-source suppliers of certain raw materials and other specialized components of production used in the manufacture and fill/finish of ~~Zimura.~~its product candidates. The Company currently relies upon a single third-party contract manufacturer to produce small quantities of the active pharmaceutical ingredient for its HtrA1 inhibitors. If the Company’s third-party manufacturers or fill/finish service providers should become unavailable to the Company for any reason, including as a result of capacity constraints, financial difficulties or insolvency, the Company believes that there are a limited number of potential replacement manufacturers, and the Company likely would incur added costs and delays in identifying or qualifying such replacements.

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Foreign Currency Translation

The Company considers the U.S. dollar to be its functional currency. Expenses denominated in foreign currencies are translated at the exchange rate on the date the expense is incurred. The effect of exchange rate fluctuations on translating foreign currency assets and liabilities into U.S. dollars is included in the Consolidated Statements of ~~Operations.~~Operations and Comprehensive Loss. Foreign exchange transaction gains and losses are included in the results of operations and are not material in the ~~Company’s~~Company's financial statements.

Financial Instruments

Cash equivalents and available for sale securities are reflected in the accompanying financial statements at fair value. The carrying amount of accounts payable and accrued expenses, including accrued research and development expenses, approximates fair value due to the short-term nature of those instruments.

Leases

The Company has leased its office space and has entered into various other agreements in conducting its business. At inception, the Company determines whether an agreement represents a lease and at commencement evaluates each lease agreement to determine whether the lease is an operating or financing lease. Some of the Company's lease agreements have contained renewal options, tenant improvement allowances, rent holidays and rent escalation clauses, although its remaining outstanding lease for its principal offices has no further options, allowances, holidays or clauses. As described below under "Recently Adopted Accounting Pronouncements," the Company adopted the Financial Accounting Standards Board (“FASB”) Accounting Standards Update (“ASU”) 2016-02, Leases (Topic 842) as of January 1, 2019.

Pursuant to ASU 2016-02, all of the Company's leases outstanding on January 1, 2019 continued to be classified as operating leases. With the adoption of ASU 2016-02, the Company recorded an operating lease right-of-use asset and an operating lease liability on its Consolidated Balance Sheet. Right-of-use lease assets represent the Company's right to use the underlying asset for the lease term and the lease obligation represents the Company's commitment to make the lease payments arising from the lease. Right-of-use lease assets and obligations are recognized at the commencement date based on the present value of remaining lease payments over the lease term. As the Company’s leases do not provide an implicit discount rate, the Company has used an estimated incremental borrowing rate based on the information available at the commencement date in determining the present value of lease payments. The right-of-use lease asset includes any lease payments made prior to commencement and excludes any lease incentives. The lease term may include options to extend or terminate the lease when it is reasonably certain that the Company will exercise that option. Operating lease expense is recognized on a straight-line basis over the lease term, subject to any changes in the lease or expectations regarding the terms. Variable lease costs such as common area costs and property taxes are expensed as incurred. For all office lease agreements the Company combines lease and nonlease components. Leases with an initial term of 12 months or less are not recorded on the Company's Consolidated Balance Sheet.

Prior to the adoption of ASU 2016-02, when the Company's lease agreements contained renewal options, tenant improvement allowances, rent holidays and rent escalation clauses, the Company recorded a deferred rent asset or liability equal to the difference between the rent expense and the future minimum lease payments due. The lease expense related to operating leases was recognized on a straight-line basis in the Company's Consolidated Statements of Operations over the term of each lease. In cases where the lessor granted the Company leasehold improvement allowances that reduced the Company's lease expense, the Company capitalized the improvements as incurred and recognized deferred rent, which was amortized over the shorter of the lease term or the expected useful life of the improvements.

Property and Equipment

Property and equipment, which consists mainly of manufacturing and clinical equipment, furniture and fixtures, computers, software, ~~and~~ other office equipment, and leasehold improvements, are carried at cost less accumulated depreciation. Depreciation is computed over the estimated useful lives of the respective assets, generally three to ten years, using the straight-line method. Amortization of leasehold improvements is recorded over the shorter of the lease term or estimated useful life of the related asset.

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Research and Development

~~Research~~The Company's research and development expenses primarily consist of costs associated with the manufacturing, development and clinical testing of Zimura, ~~and Fovista as well as~~ costs associated with the preclinical development of ~~other product candidates~~IC-100 and ~~formulations. Research~~IC-200, including related sponsored research with Penn, and costs associated with the Company's ongoing gene therapy sponsored research programs with UMMS. The Company's research and development expenses consist of:

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external research and development expenses incurred under arrangements with third parties, such as academic research collaborators, contract research organizations ~~(“CROs”~~("CROs"), and contract development and manufacturing organizations ("CDMOs") and other vendors ~~and contract manufacturing organizations (“CMOs”)~~ for the production of drug substance and drug product; and

employee-related expenses for employees dedicated to research and development activities, including salaries, benefits and share-based compensation expense.

Research and development expenses also include costs of acquired product licenses, in-process research and development, and related technology rights where there is no alternative future use, costs of prototypes used in research and development, consultant fees and amounts paid to collaborative partners.

All research and development expenses are charged to operations as incurred in accordance with ~~Financial Accounting Standards Board Accounting Standards Codification Topic, or~~ ASC 730, Research and Development. The Company accounts for non-refundable advance payments for goods and services that will be used in future research and development activities as expenses when the service has been performed or when the goods have been received, rather than when the payment is made.

Income Taxes

The Company utilizes the liability method of accounting for deferred income taxes, as set forth in ASC 740, Income Taxes. Under this method, deferred tax assets and liabilities are recognized for the expected future tax consequences of temporary differences between the carrying amounts and the tax basis of assets and liabilities. A valuation allowance is established against deferred tax assets when, based on the weight of available evidence, it is more likely than not that some or all of the deferred tax assets will not be realized. The Company's policy is to record interest and penalties on uncertain tax positions as income tax expense.

Share-Based Compensation

The Company follows the provisions of ASC 718, Compensation—Stock Compensation, which requires the measurement and recognition of compensation expense for all share-based payment awards made to employees and non-employee directors, including employee stock options, restricted stock units (“RSUs”) and ~~the option~~options granted to employees to purchase shares under the 2016 Employee Stock Purchase Plan (the “ESPP”). Share-based compensation expense is based on the grant date fair value estimated in accordance with the provisions of ASC 718 and is generally recognized as an expense over the requisite service period, net of estimated forfeitures. For grants containing performance-based vesting provisions, expense is recognized over the estimated achievement ~~period.~~period only when the performance-based milestone is deemed probable of achievement. If performance-based milestones are later determined not to be probable of achievement, then all previously recorded stock-based compensation expense associated with such options will be reversed during the period in which the Company makes this determination.

Prior to January 1, 2019, stock-based compensation awarded to non-employees was subject to revaluation over its vesting terms. Subsequent to the adoption of ASU 2018-07, Improvements to Non-Employee Share-Based Payment Accounting, non-employee share-based payment awards are measured on the date of grant, similar to share-based payment awards granted to employees.

Stock Options

The Company estimates the fair value of stock options granted to employees and non-employee directors on the date of grant using the Black-Scholes option-pricing model. Due to the lack of trading history, the ~~Company’s~~Company's computation of stock-price volatility is based on the volatility rates of comparable publicly held companies over a period equal to the expected term of the options granted by the Company. The ~~Company’s~~Company's computation of expected term is determined using the ~~“simplified”~~"simplified" method, which is the midpoint between the vesting date and the end of the contractual term. The Company believes that it does not have sufficient reliable exercise data in order to justify the use of a method other than the ~~“simplified”~~"simplified" method of estimating the expected exercise term of employee stock option grants. The Company utilizes a dividend yield of zero based on the fact that the Company has never paid cash dividends to stockholders and has no current intentions to pay cash dividends. The risk-free interest rate is based on the zero-coupon U.S. Treasury yield at the date of grant for a term equivalent to the expected term of the option.

~~For stock options granted as consideration for services rendered by consultants, the Company recognizes expense in accordance with the requirements of ASC 505-50,~~ ~~Equity Based Payments to Non-Employees~~. Consultant stock option grants are recorded as an expense over the vesting period of the underlying stock options. At the end of each financial reporting period prior to vesting, the value of these options, as calculated using the Black-Scholes option-pricing model, will be re-measured using the fair value of the Company’s common stock and the non-cash expense recognized during the period will be adjusted accordingly. Since the fair value of options granted to consultants is subject to change in the future, the amount of the future expense will include fair value re-measurements until the stock options are fully vested.

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The weighted-average assumptions used to estimate grant date fair value of stock options using the Black-Scholes option pricing model were as follows for the three ~~and nine~~ months ended ~~September 30, 2017~~March 31, 2019 and ~~2016:~~

2018:


	Three months ended September 30,		Nine months ended September 30,		Three Months Ended March 31,
	2017	2016	2017	2016	2019	2018
Expected common stock price volatility	82%	71%	81%	71%	86%	81%
Risk-free interest rate	1.95%-2.06%	1.14% -1.32%	1.82%-2.38%	1.14%-1.92%	2.50%-2.54%	2.39%-2.65%
Expected term of options (years)	6.1	6.0	6.1	6.1	6.2	5.9
Expected dividend yield	—	—	—	—	—	—

RSUs

The Company estimates the fair value of RSUs granted to employees using the closing market price of the ~~Company’s~~Company's common stock on the date of grant.

ESPP

In April 2016, the board of directors adopted the ESPP pursuant to which the Company may sell up to an aggregate of 1,000,000 shares of common stock. The ESPP was approved by the Company’s stockholders in June 2016. The ESPP is considered compensatory and the fair value of the discount and look back provision are estimated using the Black-Scholes option-pricing model and recognized over the six month withholding period prior to purchase.

Share-based compensation expense includes expenses related to stock options and RSUs granted to employees, non-employee directors and consultants, as well as the option granted to employees to purchase shares under the ESPP, all of which have been reported in the Company’s Statements of Operations as follows:

Three months ended September 30, Nine months ended September 30,
2017 2016 2017 2016

Research and development $ 1,840
$ 5,664
$ 8,887
$ 16,732
General and administrative 1,571
2,584
5,576
8,157
Total $ 3,411
$ 8,248
$ 14,463
$ 24,889

~~Recent~~Recently Adopted Accounting Pronouncements

~~In May 2014, the Financial Accounting Standards Board, or FASB, issued Accounting Standards Update, or ASU, No. 2014-9,~~ ~~Revenue from Contracts with Customers (Topic 606)~~ (“ASU 2014-9”). ASU 2014-9 outlines a new, single comprehensive model for entities to use in accounting for revenue arising from contracts with customers and supersedes most current revenue recognition guidance, including industry-specific guidance. This new revenue recognition model provides a five-step analysis in determining when and how revenue is recognized. The new model will require revenue recognition to depict the transfer of promised goods or services to customers in an amount that reflects the consideration a company expects to receive in exchange for those goods or services. The FASB subsequently issued additional clarifying standards to address issues arising from implementation of the new revenue standard, including a one-year deferral of the effective date for the new revenue standard. Public companies should now apply the guidance in ASU 2014-9 to annual reporting periods beginning after December 15, 2017 and interim periods within those annual periods. Earlier application is permitted only as of annual reporting periods beginning after December 15, 2016, including interim periods within that annual period. Companies may use either a full retrospective or a modified retrospective approach to adopt ASU 2014-9. Due to the recent development and termination of the Company's collaboration contracts with Novartis, the Company does not expect the standard to have a material impact upon adoption.

In February 2016, the FASB issued ASU No. 2016-2, Leases (Topic 842). Under the new guidance, lessees will be required to recognize the following for all leases (with the exception of short-term leases) at the commencement date: (1) a lease liability, which is a lessee’s obligation to make lease payments arising from a lease, measured on a discounted basis; and (2) a right-of-use asset, which is an asset that represents the lessee’s right to use, or control the use of, a specified asset for the

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lease term. Under the new guidance, lessor accounting is largely unchanged. Certain targeted improvements were made to align, where necessary, lessor accounting with the lessee accounting model and Topic 606, Revenue from Contracts with Customers. The new lease guidance simplified the accounting for sale and leaseback transactions primarily because lessees must recognize lease assets and lease liabilities. Lessees will no longer be provided with a source of off-balance sheet financing. Publicly-traded business entities should apply the amendments in ASU 2016-2 for fiscal years beginning after December 15, 2018, including interim periods within those fiscal years (i.e., January 1, 2019, for a calendar year entity). Early application is permitted for all publicly-traded business entities and all nonpublicly-traded business entities upon issuance. Lessees (for capital and operating leases) and lessors (for sales-type, direct financing, and operating leases) must apply a modified retrospective transition approach for leases existing at, or entered into after, the beginning of the earliest comparative period presented in the financial statements. The modified retrospective approach would not require any transition accounting for leases that expired before the earliest comparative period presented. Lessees and lessors may not apply a full retrospective transition approach. On January 1, 2019 the Company adopted this guidance utilizing the simplified transition option that allows companies to initially apply the new lease standard at the adoption date and recognize a cumulative-effect adjustment to the opening balance of retained earnings in the period of adoption. The Company elected to adopt the package of practical expedients permitted in Accounting Standards Codification Topic 842, or ASC 842. Accordingly, the Company continues to account for its existing operating leases as operating leases under the new guidance, without reassessing whether the contracts contain a lease under ASC 842 or whether classification of the operating leases would be different under ASC Topic 842.

As a result of the adoption, the Company recognized, as of the beginning of the period of adoption, right-of-use assets and lease liabilities of approximately $1.5 million, which represents the present value of its remaining lease payments using a weighted average estimated incremental borrowing rate of 6%, on its Consolidated Balance Sheet. The adoption of this standard did not have a material impact on the Company’s results of operations for the period ended March 31, 2019.

In June 2018, the FASB issued ASU No. 2018-07, Improvements to Nonemployee Share-Based Payment Accounting, which supersedes ASC 505-50 and expands the scope of ASC 718 to include all share-based payments arrangements related to the acquisition of goods and services from both employees and nonemployees. For public companies, the amendments are effective for annual reporting periods beginning after December 15, 2018, including interim periods within those annual periods. During the three months ended March 31, 2019, the Company adopted this guidance. The adoption did not have a material impact on its financial statements for the period ended and as of March 31, 2019.

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Recent Accounting Pronouncements

In August 2018, the FASB issued ASU No. 2018-13, Fair Value Measurement (Topic 820), which modifies the disclosure requirements on fair value measurements in Topic 820, Fair Value Measurement, including, among other changes, the consideration of costs and benefits when evaluating disclosure requirements. For public companies, the amendments are effective for annual reporting periods beginning after December 15, 2019, including interim periods within those annual periods. Early adoption is permitted. The Company is currently assessing the impact that adopting this new accounting guidance will have on its financial statements and footnote disclosures.

In August ~~2016,~~2018, the FASB issued ASU No. ~~2016-15,~~2018-15, ~~Statement~~Intangibles - Goodwill and Other - Internal-Use Software (Subtopic 350-40): Customer’s Accounting for Implementation Costs Incurred in a Cloud Computing Arrangement That Is a Service Contract (a consensus of ~~Cash Flows~~the FASB Emerging Issues Task Force). ASU 2018-15 aligns the requirements for capitalizing implementation costs incurred in a hosting arrangement that is a service contract with the requirements for capitalizing implementation costs incurred to develop or obtain internal-use software (and hosting arrangements that include an internal-use software license). This guidance is effective for fiscal years beginning after December 15, 2019, and for interim periods within those fiscal years, with early adoption permitted. The Company is currently evaluating the potential effects of this guidance on its consolidated financial statements.

In November 2018, the FASB issued ASU No. 2018-18, Collaborative Arrangements (Topic ~~230): Classification of Certain Cash Receipts and Cash Payments~~808), which clarifies the ~~presentation of certain specific cash flow issues in~~interaction between the ~~Statement of Cash Flows.~~guidance for collaborative arrangements (Topic 808) and the new revenue recognition standard (Topic 606). For public companies, the amendments are effective for annual reporting periods beginning after December 15, ~~2017, and~~2019, including interim periods within those annual ~~periods and early adoption is permitted. This new guidance is not expected to have a material impact on the Company’s Consolidated Financial Statements.~~

~~In January 2017, the FASB issued ASU No. 2017-01,~~ ~~Business Combinations (Topic 805): Clarifying the Definition of a Business~~, in an effort to clarify the definition of a business with the objective of adding guidance to assist entities with evaluating whether transactions should be accounted for as acquisitions (or disposals) of assets or businesses. The amendments of this ASU are effective for fiscal years beginning after December 15, 2017, and interim periods within those fiscal years.periods. Early adoption is permitted. ~~This~~The Company is currently assessing the impact that adopting this new accounting guidance will ~~be applicable for the Company’s acquisitions~~have on ~~or after January 1, 2018.~~its financial statements and footnote disclosures.

3. Net ~~Income (Loss)~~Loss Per Common Share

Basic and diluted net ~~income (loss)~~loss per common share is determined by dividing net ~~income (loss)~~loss by the weighted average common shares outstanding during the period. For the periods where there is a net loss, shares underlying stock options and RSUs have been excluded from the calculation of diluted net loss per common share because ~~their~~the effect of including such shares would be anti-dilutive. Therefore, the weighted average common shares used to calculate both basic and diluted net loss per common share would be the same. The following table sets forth the computation of basic and diluted net ~~income (loss)~~loss per common share for the periods indicated:

Three months ended September 30, Nine months ended September 30,
2017 2016 2017 2016

Basic and diluted net income (loss) per common share calculation:

Net income (loss) $ 189,073
$ (60,891 ) $ 123,747
$ (127,137 )
Weighted average common shares outstanding - basic 35,971
35,594
35,878
35,415
Plus: net effect of dilutive stock options and unvested restricted stock units 76
—
106
—
Weighted average common shares outstanding - dilutive 36,047
35,594
35,984
35,415
Net income (loss) per share of common stock - basic $ 5.26
$ (1.71 ) $ 3.45
$ (3.59 )
Net income (loss) per share of common stock - diluted $ 5.25
$ (1.71 ) $ 3.44
$ (3.59 )

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	Three Months Ended March 31,
	2019			2018
Basic and diluted net loss per common share calculation:
Net loss	$	(12,501	)	$	(13,073	)
Weighted average common shares outstanding - basic and dilutive	41,427			36,153
Net loss per share of common stock - basic and diluted	$	(0.30	)	$	(0.36	)

The following potentially dilutive securities have been excluded from the computations of diluted weighted average common shares outstanding for the periods presented, as ~~they~~the effect of including such shares would be anti-dilutive:


	Three months ended September 30,		Nine months ended September 30,
	2017	2016	2017	2016	Three Months Ended March 31,
					2019	2018
Stock options outstanding	3,640	3,423	3,813	3,423	5,844	5,021
Restricted stock units	269	721	332	721	664	228
Total	3,909	4,144	4,145	4,144	6,508	5,249

4. Cash, Cash Equivalents and Available for Sale Securities

The Company considers all highly liquid investments purchased with original maturities of 90 days or less at the date of purchase to be cash equivalents. As of March 31, 2019 and December 31, 2018, the Company had cash and cash equivalents of approximately $116.6 million and $131.2 million, respectively. Cash and cash equivalents included cash of ~~$13.2 million and $25.8~~$4.1 million at ~~September 30, 2017~~March 31, 2019 and $4.4 million at December 31, ~~2016, respectively.~~2018. Cash and cash equivalents at ~~September 30, 2017~~March 31, 2019 and December 31, ~~2016 also~~2018 included ~~$167.1~~$112.5 million and ~~$108.1~~$126.8 million, respectively, of investments in money market funds ~~U.S. Treasury securities~~ and certain ~~short-term~~ investment-grade corporate debt securities with original maturities of 90 days or less.

The Company considers securities with original maturities of greater than 90 days at the date of purchase to be available for sale securities. The Company held no available for sale securities at ~~September 30, 2017. The Company held available for sale securities with a fair value totaling $155.3 million~~March 31, 2019 or at December 31, ~~2016. These~~2018, respectively.

The Company believes that its existing cash and cash equivalents as of March 31, 2019 will be sufficient to fund its operations and capital expenditure requirements as currently planned for at least the next 12 months.

5. Share-Based Compensation

Pursuant to the evergreen provisions of the Company's 2013 stock incentive plan (the "2013 Plan"), annual increases have resulted in the addition of an aggregate of approximately 8,554,000 additional shares to the 2013 Plan, including for 2019, an increase of approximately 1,656,000 shares, or approximately 4% of the total number of shares of the Company's common stock outstanding as of January 1, 2019. As of March 31, 2019, the Company had approximately 2,544,000 shares available for ~~sale securities consisted~~grant under the 2013 Plan.

As of ~~U.S. Treasury securities and investment-grade corporate debt securities. During the quarter ended September 30, 2017, the Company's investments matured and~~March 31, 2019, there were ~~reinvested in money market funds.~~

~~Available for sale securities, including carrying value and estimated fair values as of December 31, 2016, are summarized as follows:~~

As of December 31, 2016
Cost Unrealized Gains Unrealized Losses Fair Value

U.S. Treasury securities $ 120,288
$ 6
$ (33 ) $ 120,261
Corporate debt securities 35,114
—
(27 ) 35,087
Total $ 155,402
$ 6
$ (60 ) $ 155,348

~~The Company’s~~920,707 shares available for ~~sale securities are reported at fair value on~~future purchases under the ~~Company’s Balance Sheets. Unrealized gains (losses) are reported within accumulated other comprehensive income (loss) in the statements~~ESPP.

Share-based compensation expense, net of ~~comprehensive income (loss). The cost of securities sold~~estimated forfeitures, includes expenses related to stock options and any realized gains/losses from the sale of available for sale securities are based on the specific identification method. The changes in accumulated other comprehensive income (loss) associated with the unrealized gain (loss) on available for sale securities during the threeRSUs granted to employees, non-employee directors and ~~nine months ended September 30, 2017 and September 30, 2016 were as follows:~~

Three months ended September 30, Nine months ended September 30,
2017 2016 2017 2016

Beginning balance $ (186 ) $ (118 ) $ (212 ) $ (473 )
Current period changes in fair value before reclassifications, net of tax 186
(41 ) 212
314
Amounts reclassified from accumulated other comprehensive income (loss), net of tax —
—
—
—
Total other comprehensive income (loss) 186
(41 ) 212
314
Ending balance $ —
$ (159 ) $ —
$ (159 )

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~~5. Licensing and Commercialization Agreement with Novartis Pharma AG~~

In May 2014, the Company entered into the Novartis Agreement. Under the Novartis Agreement, the Company granted Novartis exclusive rights under specified patent rights, know-how and trademarks controlled by the Company to manufacture, from bulk API supplied by the Company, standalone Fovista products and products combining Fovista with an anti-VEGF drug to which Novartis has rights in a co-formulated product, for the treatment, prevention, cure or control of any human disease, disorder or condition of the eye, and to develop and commercialize those licensed products in all countries outside of the United States (the “Novartis Territory”). The Company agreed to use commercially reasonable efforts to complete its ongoing pivotal Phase 3 clinical program for Fovista and Novartis agreed to use commercially reasonable efforts to develop a standalone Fovista product and a co-formulated product containing Fovista and an anti-VEGF drug to which Novartis has rights,consultants, as well as ~~a pre-filled syringe presentation of such products and~~options granted to ~~use commercially reasonable efforts, subject~~employees to ~~obtaining marketing approval, to commercialize licensed products~~purchase shares under the ESPP. Stock-based compensation by award type was as follows:



	Three Months Ended March 31,
	2019		2018
Stock options	$	1,622	$	2,132
Restricted stock units	821		946
Employee stock purchase plan	27		4
Total	$	2,470	$	3,082

The Company allocated stock-based compensation expense in the ~~Novartis Territory in accordance with agreed development~~Company’s Consolidated Statements of Operations and ~~marketing plans.~~Comprehensive Loss as follows:



	Three Months Ended March 31,
	2019		2018
Research and development	$	1,170	$	1,440
General and administrative	1,300		1,642
Total	$	2,470	$	3,082

Stock Options

A summary of the stock option activity, weighted average exercise prices, options outstanding, exercisable and expected to vest as of March 31, 2019 is as follows (in thousands except weighted average exercise price):



	Number of Shares Underlying Options		Weighted Average Exercise Price
Outstanding, December 31, 2018	5,903		$	13.72
Granted	52		$	1.27
Forfeited	(111	)	$	31.46
Outstanding, March 31, 2019	5,844		$	13.27
Vested and exercisable, March 31, 2019	2,833		$	22.68
Vested and expected to vest, March 31, 2019	5,603		$	13.65

As of March 31, 2019, there were approximately $7.8 million of unrecognized compensation costs, net of estimated forfeitures, related to stock option awards grants, which are expected to be recognized over a remaining weighted average period of 1.9 years.

In July 2017, the Company and Novartis entered into the Letter Agreement to streamline the process and timeline for evaluating data from the OPH1004 trial once it became available. On October 23, 2017,RSUs

The following the failure of the Phase 3 Fovista program and pursuant to the terms of the Letter Agreement, Novartis elected to terminate the Novartis Agreement with immediate effect. See "—Note 13—Subsequent Events" for a description of the termination notice.

In May 2014, Novartis paid the Company a $200.0 million upfront payment. In each of September 2014 and March 2015, the Company achieved a $50.0 million enrollment-based milestone, and in June 2016, the Company achieved a $30.0 million enrollment-based milestone, for an aggregate total of $130.0 million in enrollment-based milestones under the Novartis Agreement. The Company used the relative selling price method to allocate these payments to contract deliverables based on its performance obligations under the Novartis Agreement.

~~Activities under the Novartis Agreement were evaluated under ASC 605-25,~~ ~~Revenue Recognition—Multiple Element Arrangements~~ ~~(“ASC 605-25”) (as amended by ASU 2009-13,~~ ~~Revenue Recognition~~ (“ASU 2009-13”)) to determine if they represented a multiple element revenue arrangement. The Novartis Agreement included the following deliverables: (1) an exclusive license to commercialize Fovista outside the United States (the “License Deliverable”); (2) the performance obligation to conduct research and development activities related to the Phase 3 Fovista clinical trials and certain Phase 2 trials for Fovista (the “R&D Activity Deliverable”); (3) the performance obligation to supply API to Novartis for development and manufacturing purposes (the “Manufacturing Deliverable”) and (4) the Company’s obligation to participate on the joint operating committee established under the terms of the Novartis Agreement and related subcommittees (the “Joint Operating Committee Deliverable”). The Company’s obligation to provide access to clinical and regulatory information as part of the License Deliverable included the obligation to provide access to all clinical data, regulatory filings, safety data and manufacturing data to Novartis which was necessary for the commercialization of Fovista in the Novartis Territory. The R&D Activity Deliverable included the right and responsibility for the Company to conduct the Phase 3 Fovista clinical program and other Phase 2 studies of Fovista which were necessary or desirable for regulatory approval or commercialization of Fovista. The Manufacturing Deliverable included the obligation for the Company to supply API to Novartis for clinical purposes, for which Novartis agreed to pay the Company’s manufacturing costs. The Joint Operating Committee Deliverable included the obligation to participate in the Joint Operating Committee and related subcommittees at least through the first anniversary of regulatory approval in the European Union. All of these deliverables were deemed to have stand-alone value and to meet the criteria to be accounted for as separate units of accounting under ASC 605-25. Factors considered in this determination included, among other things, the subject of the licenses and the research and development and commercial capabilities of Novartis. Accordingly, each unit was accounted for separately.

The Novartis Agreement included a termination right for the Company in the event that specified governmental actions prevented the parties from materially progressing the development or commercialization of licensed products. If the Company elected to exercise this termination option, it would have been required to pay a substantial termination fee equivalent to the entire upfront payment amount. The Company concluded that this termination provision constituted a contingent event that was unknown at the inception of the agreement. As such, the Company recorded the $200.0 million upfront payment in deferred revenue, long-term until such time that the contingency related to this termination provision was resolved. In July 2017, the contingency was resolved when the Company permanently waived this termination right as part of the Letter Agreement.

The Letter Agreement also provided Novartis with a shorter notice period in the event Novartis determined to terminate the Novartis Agreement in certain circumstances. In addition, the Letter Agreement provided Novartis with a fully paid-up, royalty free license to use data from the Lucentis monotherapy arms of the Company's Phase 2b OPH1001 trial and Phase 3 OPH1002 and OPH1003 trials in the Novartis Territory in connection with the development, manufacturing and

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~~commercialization of Novartis-controlled anti-VEGF products. The Lucentis study data license continues until the fifth anniversary of the Letter Agreement.~~

The Company evaluated the Letter Agreement under ASC 605-25 and determined that the Letter Agreement does not create any new deliverables. The Company is treating the Fovista license granted at the inception of the Novartis Agreement and the Lucentis study data license granted under the Letter Agreement as one collective technology license (the "Licenses") delivered at the inception of the Novartis Agreement. In addition, as the waiver of its right to terminate the Novartis Agreement as a result of specified governmental actions resolved the Company’s contingency with respect to such termination right and the associated termination fee, the Company allocated the entire previously deferred amount, $200.0 million, to the deliverables that were determined based on the relative selling price at contract inception. Upon entry into the Letter Agreement in July 2017, the Company immediately recognized as revenue $189.8 million of the upfront payment allocated to contract deliverables completed during prior periods. Upon termination of the OPH1004 trial in August 2017, the Company recognized the remaining $16.9 million of collaboration revenue, attributable to the R&D Deliverable, previously deferred under the Novartis Agreement. In total, during the third quarter of 2017, the Company recognized $206.7 million in previously deferred collaboration revenue in connection with the Novartis Agreement. The recognition of this revenue during the period did not impact the Company's cash balance.

~~Below is~~table presents a summary of the ~~components~~Company's outstanding RSU awards granted as of March 31, 2019 (in thousands except weighted average grant-date fair value):



	Restricted Stock Units		Weighted Average Grant-Date Fair Value
Outstanding, December 31, 2018	679		$	15.61
Awarded	10		$	1.38
Vested	(25	)	$	60.50
Forfeited	—		$	—
Outstanding, March 31, 2019	664		$	13.82
Outstanding, Expected to vest	543		$	8.22

As of March 31, 2019, there were approximately $2.8 million of unrecognized compensation costs, net of estimated forfeitures, related to RSUs grants, which are expected to be recognized over a remaining weighted average period of 1.6 years. The total grant date fair value of the ~~Company’s collaboration revenue for~~RSUs that vested during the three ~~and nine~~ months ended ~~September 30, 2017 and September 30, 2016:~~March 31, 2019 was $31.0 thousand.

As of March 31, 2019, there were 920,707 shares available for future purchases under the ESPP. There were 31,522 shares of common stock issued under the ESPP during the three months ended March 31, 2019. Cash proceeds from ESPP purchases were $42 thousand during the three months ended March 31, 2019. There were 12,229 shares of common stock issued under the ESPP during the three months ended March 31, 2018. Cash proceeds from ESPP purchases were $27 thousand during the three months ended March 31, 2018.

6. ~~Financing Agreement with Novo A/S~~

In May 2013, the Company entered into a Purchase and Sale Agreement with Novo A/S, which is referred to as the Novo Agreement, pursuant to which the Company had the ability to obtain financing in three tranches in an amount of up to $125.0 million in return for the sale to Novo A/S of aggregate royalties of worldwide sales of (a) Fovista, (b) Fovista-Related Products, and (c) Other Products (each as defined in the Novo Agreement), calculated as mid-single digit percentages of net sales.

The Novo Agreement provided for up to three separate purchases for a purchase price of $41.7 million each, at a first, second and third closing, for an aggregate purchase price of $125.0 million. In each purchase, Novo A/S would acquire rights to a low single digit percentage of net sales. In each of May 2013, January 2014 and November 2014, the Company received cash payments of $41.7 million, or $125.0 million in the aggregate, and Novo A/S received, in the aggregate, a right to receive royalties on net sales of Fovista at a mid-single digit percentage.

The royalty payment period covered by the Novo Agreement begins on commercial launch and ends, on a product-by-product and country-by-country basis, on the latest to occur of (i) the 12th anniversary of the commercial launch, (ii) the expiration of certain patent rights and (iii) the expiration of the regulatory exclusivity for each product in each country. The Company's obligations under the Novo agreement are secured by a lien on certain of the Company's intellectual property and other rights related to Fovista and other anti-PDGF products the Company may develop.

Under the terms of the Novo Agreement, the Company is not required to reimburse or otherwise compensate Novo A/S through any means other than the agreed royalty entitlement. In addition, the Company does not, under the terms of the Novo Agreement, have the right or obligation to prepay Novo A/S in connection with a change of control of the Company or otherwise.

The $125.0 million in aggregate proceeds from the three financing tranches under the Novo Agreement represents the full funding available under the Novo Agreement, and has been recorded as a liability on the Company’s Balance Sheet as of

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~~September 30, 2017, in accordance with ASC 730,~~ ~~Research and Development~~. Because there is a significant related party relationship between the Company and Novo A/S, the Company is treating its obligation to make royalty payments under the Novo Agreement as an implicit obligation to repay the funds advanced by Novo A/S. As the Company makes royalty payments in accordance with the Novo Agreement, it will reduce the liability balance. At the time that such royalty payments become probable and estimable, and if such amounts exceed the liability balance, the Company will impute interest accordingly on a prospective basis based on such estimates.

The Novo Agreement requires the establishment of a Joint Oversight Committee in the event that Novo A/S does not continue to have a representative on the Company’s board of directors. The Joint Oversight Committee would have responsibilities that include “discussion and review” of all matters related to Fovista research, development, regulatory approval and commercialization, but there is no provision either implicit or explicit that gives the Joint Oversight Committee or its members decision-making authority.

7. Income Taxes

For the three ~~and nine~~ months ended ~~September 30, 2017,~~March 31, 2019, the Company recorded a de minimis provision for income taxes. For the three months ended March 31, 2018, the Company recorded a provision for income taxes of $0.2 million primarily ~~due~~ to ~~discrete income tax items associated with changes~~reflect a reduction in the fair value of the Company's available for sale marketable securities which are reflected in other comprehensive income (loss). Although the Company had $189.3 million and $123.9 million of net income before income taxes for the three and nine months ended September 30, 2017 as a result of the recognition of deferred revenue under the Novartis Agreement, the Company expects a net loss for tax purposes for 2017 with minimal taxes due. For tax purposes, the Company treated payments received under the Novartis Agreement as revenue at the time the payments were received. The Company recorded a provision for income taxes of $0.1 million for the three months ended September 30, 2016, and a benefit from income taxes of $0.2 million for the nine months ended September 30, 2016 primarily due to discrete income tax items in each period associated with changes in the fair value of the Company's available for sale marketable securities which are reflected in other comprehensive income (loss).

~~In the second quarter of 2017, the IRS concluded an audit of the Company’s U.S. federal income tax returns for the years 2013, 2014 and 2015, resulting in an immaterial~~ amount of ~~additional tax due. Federal net operating losses for 2016 and general business credits generated between 2007 and 2016 remain subject to audit.~~

During the nine months ended September 30, 2017, the Company amended certain state and local income tax returns to claim a refund for taxes previously paid. These claims may result in refunds to the Company of up to approximately $7.9 million. As the Company believes that the likelihood of its position in claiming the refunds does not rise to the level of more likely than not at this time, the Company has not recorded a current tax receivable for the refund claims as of September 30, 2017.

~~The Company considers all available evidence, both positive and negative, to determine whether, based on the weight of that evidence, a valuation allowance is needed to reduce its~~ deferred tax assets ~~to the amount that is more likely than not~~expected to be realized. The Company placed significant weight on the fact that the Company expects to be in a cumulative net book loss position for the three-year period ending December 31, 2017 in recording valuation allowances on its deferred tax assets as of September 30, 2017.

~~Pursuant to ASC 740,~~ ~~Income Taxes~~, the Company routinely evaluates the likelihood of success if challenged on income tax positions claimed on its income tax returns. During the three months ended September 30, 2017, the Company reduced certain deferred tax assets by $5.9 million and reduced the corresponding valuation allowance by an equivalent amount. During the three months ended September 30, 2016, the Company reduced certain deferred tax assets by $3.8 million and reduced the corresponding valuation allowance by an equivalent amount. These items have not been recognizedrealized in the financial statements and if disallowed by the tax authorities, would not result in an adjustment to the Company’s effective tax rate, its balance sheet or its cash flow statements for the current year.

future.

The Company will continue to evaluate its ability to realize its deferred tax assets on a ~~periodic~~quarterly basis and will adjust such amounts in light of changing facts and circumstances including, but not limited to, future projections of taxable income, tax legislation, rulings by relevant tax authorities, the progress of ongoing tax audits and the regulatory approval of products currently under development. Any additional changes to the valuation allowance recorded on deferred tax assets in the future would impact the Company’s income taxes.

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8.7. Fair Value Measurements

ASC 820, Fair Value Measurements and Disclosures ~~(“ASC 820”)~~, defines fair value as the price that would be received to sell an asset, or paid to transfer a liability, in the principal or most advantageous market in an orderly transaction between market participants on the measurement date. The fair value standard also establishes a three-level hierarchy, which requires an entity to maximize the use of observable inputs and minimize the use of unobservable inputs when measuring fair value.

The Company reviews investments on a periodic basis for other than temporary impairments. This review is subjective as it requires management to evaluate whether an event or change in circumstances has occurred in the period that may have a significant adverse effect on the fair value of the investment. The Company uses the market approach to measure fair value for its financial assets. The market approach uses prices and other relevant information generated by market transactions involving identical or comparable assets. The Company classifies its investment-grade corporate debt securities within the fair value hierarchy as Level 2 assets, as it primarily utilizes quoted market prices or rates for similar instruments to value these securities.

The valuation hierarchy is based upon the transparency of inputs to the valuation of an asset or liability on the measurement date. The three levels are defined as follows:

Level 1—inputs to the valuation methodology are quoted prices (unadjusted) for an identical asset or liability in an active market. The ~~Company’s~~Company's Level 1 assets consist of investments in money market funds and U.S. Treasury securities.

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Level 2—inputs to the valuation methodology include quoted prices for a similar asset or liability in an active market or model-derived valuations in which all significant inputs are observable for substantially the full term of the asset or liability. The ~~Company’s~~Company's Level 2 assets may consist of investments in investment-grade corporate debt securities.

Level 3—inputs to the valuation methodology are unobservable and significant to the fair value measurement of the asset or liability. The Company does not hold any assets that are measured using Level 3 inputs.

The following table presents, for each of the fair value hierarchy levels required under ASC 820, the Company's assets and liabilities that are measured at fair value on a recurring basis as of March 31, 2019:



	Fair Value Measurement Using
	Quoted prices in active markets for identical assets (Level 1)		Significant other observable inputs (Level 2)		Significant unobservable inputs (Level 3)
Assets
Investments in money market funds*	$	93,761	$	—	$	—
Investments in investment-grade corporate debt securities*	$	—	$	18,731	$	—

The following table presents, for each of the fair value hierarchy levels required under ASC 820, the ~~Company’s assets and liabilities that are measured at fair value on a recurring basis as of September 30, 2017:~~

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~~The following table presents, for each of the fair value hierarchy levels required under ASC 820, the Company’s~~Company's assets and liabilities that are measured at fair value on a recurring basis as of December 31, ~~2016:~~

2018:

Fair Value Measurement Using

Quoted prices in
active markets for
identical assets
(Level 1)

Significant other
observable inputs
(Level 2)

Significant
unobservable
inputs
(Level 3)

Assets

Investments in money market funds* $ 108,096
$ —
$ —
Investments in U.S. Treasury securities $ 120,261
$ —
$ —
Investments in Corporate debt securities $ —
$ 35,087
$ —



	Fair Value Measurement Using
	Quoted prices in active markets for identical assets (Level 1)		Significant other observable inputs (Level 2)		Significant unobservable inputs (Level 3)
Assets
Investments in money market funds*	$	97,402	$	—	$	—
Investments in Corporate debt securities	$	—	$	29,425	$	—


*	Investments in money market funds and investment-grade corporate debt securities with maturities less than 90 days are reflected in cash and cash equivalents in the accompanying Balance Sheets.

* Investments in money market funds, U.S. Treasury securities and corporate debt securities with maturities less than 90 days are reflected in cash and cash equivalents in the accompanying Balance Sheets.

No transfer of assets between Level 1 and Level 2 of the fair value measurement hierarchy occurred during the three ~~and nine~~ months ended ~~September 30, 2017.~~March 31, 2019.

The Company held no available for sale securities at March 31, 2019 or at December 31, 2018.

~~9. Stock Option and Compensation Plans~~

8. Operating Leases

The Company ~~adopted its 2007 Stock Incentive Plan (the “2007 Plan”) for employees, non-employee directors~~leases office space located in New York, New York and ~~consultants~~Princeton, New Jersey under non-cancelable operating lease arrangements. The lease for the ~~purpose~~Company's New York office space expires at the end of ~~advancing~~June 2020, whereas the ~~interests of the Company’s stockholders by enhancing its ability to attract, retain and motivate persons who are expected to make important contributions to the Company. The 2007 Plan provided~~sublease for the ~~granting of stock option awards, RSUs, and other stock-based and cash-based awards. Following the effectiveness of the 2013 Stock Incentive Plan described below~~Company's Princeton office space expires in ~~connection with the closing of the Company’s initial public offering, the Company is no longer granting additional awards under the 2007 Plan.~~

In August 2013, the Company’s board of directors adopted and the Company’s stockholders approved the 2013 stock incentive plan (the “2013 Plan”), which became effective immediately prior to the closing of the Company’s initial public offering. In June 2015, the Company’s board of directors adopted a first amendment to the 2013 Plan. The 2013 Plan provides for the grant of incentive stock options, nonstatutory stock options, stock appreciation rights, RSUs, restricted stock awards and other stock-based awards. Upon the effectiveness of the 2013 Plan, the number of shares of the Company’s common stock that were reserved for issuance under the 2013 Plan was the sum of (1) such number of shares (up to approximately 3,359,641 shares) as is equal to the sum of 739,317 shares (the number of shares of the common stock then available for issuance under the 2007 Plan), and such number of shares of the Company’s common stock that are subject to outstanding awards under the 2007 Plan that expire, terminate or are otherwise surrendered, canceled, forfeited or repurchased by the Company at their original issuance price pursuant to a contractual repurchase right plus (2) an annual increase, to be added the first business day of each fiscal year, beginning with the fiscal year ending December 31, 2014 and continuing until, and including, the fiscal year ending December 31, 2023, equal to the lowest of 2,542,372 shares of the Company’s common stock, 4% of the number of shares of the Company’s common stock outstanding on the first day of the fiscal year and an amount determined by its board of directors. The Company’s employees, officers, directors, consultants and advisors are eligible to receive awards under the 2013 Plan. However, incentive stock options may only be granted to employees of the Company.

Annual increases under the evergreen provisions of the 2013 Plan have resulted in the addition of an aggregate of approximately 5,454,000 additional shares to the 2013 Plan, including for 2017, an increase of approximately 1,429,000 shares, or 4% of the total number of shares of the Company's common stock outstanding asMarch 2020. As of January 1, ~~2017. As of September 30, 2017,~~2019, the Company ~~had~~recognized right-of-use assets and lease liabilities of approximately ~~2,124,000 shares available for grant under~~$1.5 million, which represents the ~~2013 Plan.~~

In April 2016, the board of directors adopted the ESPP pursuant to which the Company may sell up to an aggregate of 1,000,000 shares of common stock. The ESPP was approved by the Company’s stockholders in June 2016. The ESPP allows eligible employees to purchase common stock at a price per share equal to 85% of the lower of the fair marketpresent value of its remaining lease payments using a weighted average estimated incremental borrowing rate of 6%.

For the ~~common stock at~~three months ended March 31, 2019, lease and rent expense was $0.3 million. Cash paid from operating cash flows for amounts included in the ~~beginning or end~~measurement of ~~each six month offering period during~~lease liabilities was $0.3 million for the three months ended March 31, 2019. At March 31, 2019, the Company's operating leases had a weighted average remaining lease term of ~~the ESPP. The first offering period began in September 2016.~~

~~A summary of the stock option activity, weighted average exercise prices, options outstanding and exercisable as of September 30, 2017 is as follows:~~1.2 years.

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The following presents the maturity of the Company's operating lease liabilities as of March 31, 2019:

Common
Stock
Options

Weighted
Average
Exercise
Price

Outstanding, December 31, 2016 3,359
$ 39.92
Granted 1,294
$ 4.25
Exercised (20 ) $ 1.64
Expired or forfeited (995 ) $ 38.79
Outstanding, September 30, 2017 3,638
$ 27.74

Options exercisable at September 30, 2017
1,839
Weighted average grant date fair value (per share) of options granted during the period
$ 2.95

As of September 30, 2017, there were approximately 3,354,000 options outstanding, net of estimated forfeitures that had vested or are expected to vest. The weighted average exercise price of these options was $28.48 per option; the weighted average remaining contractual life of these options was 7.5 years; and the aggregate intrinsic value of these options was approximately $0.1 million.

~~A summary of the stock options outstanding and exercisable as of September 30, 2017 is as follows:~~

As of September 30, 2017
Options Outstanding Options Exercisable
Range of Exercise Prices
Total
Options
Outstanding

Weighted
Average
Remaining
Life (Years)

Weighted
Average
Exercise
Price

Number
Exercisable

Weighted
Average
Exercise
Price

$0.12-$10.03 1,364
8.8 $ 4.63
194
$ 6.93
$10.04-$20.00 204
5.7 $ 13.52
147
$ 13.63
$20.01-$30.00 127
6.1 $ 25.13
122
$ 25.14
$30.01-$40.00 836
5.8 $ 32.81
759
$ 32.89
$40.01-$55.00 727
7.8 $ 46.47
431
$ 46.11
$55.01-$73.22 380
8.3 $ 72.18
186
$ 71.13
3,638
7.6 $ 27.74
1,839
$ 35.07

Aggregate Intrinsic Value $ 114

$ 95

~~Cash proceeds from, and the aggregate intrinsic value of, stock options exercised during the three and nine months ended September 30, 2017 and 2016, respectively, were as follows:~~

Three months ended September 30, Nine months ended September 30,
2017 2016 2017 2016

Cash proceeds from options exercised $ —
$ 1,591
$ 33
$ 5,398
Aggregate intrinsic value of options exercised $ —
$ 5,185
$ 43
$ 12,607

In connection with stock option awards granted to employees, the Company recognized approximately $2.3 million and $5.6 million in share-based compensation expense during the three months ended September 30, 2017 and 2016, respectively, net of expected forfeitures. In connection with stock option awards granted to employees, the Company recognized approximately $10.3 million and $17.3 million in share-based compensation expense during the nine months ended September 30, 2017 and 2016, respectively, net of expected forfeitures. As of September 30, 2017, there were approximately $15.0 million of unrecognized compensation costs, net of estimated forfeitures, related to stock option awards granted to employees, which are expected to be recognized over a remaining weighted average period of 2.2 years.

In connection with stock option awards granted to consultants, the Company recognized approximately $0.1 million and $0.6 million in share-based compensation expense during the three months ended September 30, 2017 and 2016, respectively, net of expected forfeitures. In connection with stock option awards granted to consultants, the Company

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recognized approximately $0.3 million and $1.5 million in share-based compensation expense during the nine months ended September 30, 2017 and 2016, respectively, net of expected forfeitures. As of September 30, 2017, there were approximately $0.2 million of unrecognized compensation costs, net of estimated forfeitures, related to stock option awards granted to consultants, which are expected to be recognized over a remaining weighted average period of 1.9 years.

~~The following table presents a summary of the Company’s outstanding RSU awards granted as of September 30, 2017:~~

Restricted
Stock
Units

Weighted
Average
Grant-Date
Fair Value

Outstanding, December 31, 2016 721
$ 55.33
Awarded 248
$ 4.42
Vested (263 ) $ 24.24
Forfeited (288 ) $ 50.17
Outstanding, September 30, 2017 418
$ 42.85

As of September 30, 2017, there were approximately 262,000 RSUs outstanding, net of estimated forfeitures that are expected to vest. The weighted average fair value of these RSUs was $36.82 per share and the aggregate fair value of these RSUs was approximately $0.7 million.

In connection with RSUs granted to employees, the Company recognized approximately $0.9 million and $2.0 million in share-based compensation expense during the three months ended September 30, 2017 and 2016, respectively, net of expected forfeitures. In connection with RSUs granted to employees, the Company recognized approximately $3.4 million and $6.1 million in share-based compensation expense during the nine months ended September 30, 2017 and 2016, respectively, net of expected forfeitures. As of September 30, 2017, there were approximately $6.8 million of unrecognized compensation costs, net of estimated forfeitures, related to RSUs granted to employees, which are expected to be recognized over a remaining weighted average period of 2.2 years.

In connection with RSUs granted to consultants, the Company recognized approximately $0.1 million in share-based compensation expense during the three months ended September 30, 2017, net of expected forfeitures. In connection with RSUs granted to consultants, the Company recognized $0.3 million of share-based compensation expense during the nine months ended September 30, 2017, net of expected forfeitures. There were no RSUs granted to consultants during the three and nine months ended September 30, 2016. As of September 30, 2017, there were approximately $0.1 million of unrecognized compensation costs, net of estimated forfeitures, related to RSUs granted to consultants, which are expected to be recognized over a remaining weighted average period of 1.9 years.

In connection with the ESPP made available to employees, the Company recognized a de minimis amount of share-based compensation expense during the three months ended September 30, 2017 and 2016, respectively, net of expected forfeitures. In connection with the ESPP made available to employees, the Company recognized $0.1 million and a de minimis amount of share-based compensation expense during the nine months ended September 30, 2017 and 2016, respectively, net of expected forfeitures. As of September 30, 2017, there was a de minimis amount of unrecognized compensation costs, net of estimated forfeitures, related to the ESPP, which are expected to be recognized over 0.5 years. There were 11,612 and 16,358 shares of common stock issued under the ESPP during the three and nine months ended September 30, 2017. Cash proceeds from ESPP purchases were $25 thousand and $38 thousand during the three and nine months ended September 30, 2017. There were no shares of common stock issued under the ESPP plan during the three and nine months ended September 30, 2016, as the first offering period under the ESPP commenced in September 2016. As of September 30, 2017, 983,642 shares were available for future purchases under the ESPP.

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~~10. Property and Equipment~~

~~Property and equipment as of September 30, 2017 and December 31, 2016 were as follows:~~

Useful Life
(Years)
September 30,
2017 December 31, 2016

Manufacturing and clinical equipment 7 - 10 $ 412
$ 617
Computer, software and other office equipment 5 1,711
1,711
Furniture and fixtures 1 - 7 774
774
Leasehold improvements 1 - 5 1,835
1,835
4,732
4,937
Accumulated depreciation (3,430 ) (1,656 )
Property and equipment, net $ 1,302
$ 3,281

For the three and nine months ended September 30, 2017, depreciation expense was $0.6 million and $2.0 million, respectively. For the three and nine months ended September 30, 2016, depreciation expense was $0.2 million and $0.5 million, respectively.



	March 31, 2019
Remainder of 2019	$	780
2020	504
Total remaining obligation	1,284
Less imputed interest	(54		)
Present value of lease liabilities	$	1,230

~~11.~~9. Commitments and Contingencies

Zimura - Archemix Corp.

~~Under various agreements,~~The Company is party to an agreement with Archemix Corp., or Archemix, under which the Company in-licensed rights in certain patents, patent applications and other intellectual property related to Zimura and pursuant to which the Company may be required to pay ~~royalties~~sublicense fees and make milestone ~~payments. These agreements include~~payments (the "C5 License Agreement"). Under the ~~following:~~

~~Under a license agreement with Archemix with respect to pharmaceutical products comprised of or derived from anti-C5 aptamers,~~C5 License Agreement, for each anti-C5 aptamer product that the Company may develop under the agreement, including Zimura, the Company is obligated to make ~~future~~ payments to Archemix of up to an aggregate of $57.5 million if the Company achieves specified development, clinical and regulatory milestones, with $30.5 million of such payments relating to a first indication, $24.5 million of such payments relating to second and third indications and $2.5 million of such payments relating to sustained delivery applications. Under the C5 License Agreement, the Company is also obligated to make additional payments to Archemix of up to an aggregate of $22.5 million if the Company achieves specified commercial ~~milestones.~~milestones based on net product sales of all anti-C5 products licensed under the agreement. The Company is also obligated to pay Archemix a double-digit percentage of specified non-royalty payments the Company may receive from any sublicensee of ~~the Company’s~~its rights under ~~this license agreement. No royalties are payable~~the C5 License Agreement. The Company is not obligated to pay Archemix ~~under this license agreement.~~a running royalty based on net product sales in connection with the C5 License Agreement.

IC-100 - University of Florida and the University of Pennsylvania

Under ~~the Company’s divestiture~~its exclusive license agreement with ~~OSI (Eyetech), Inc., which agreement is now held by OSI Pharmaceuticals, LLC., or OSI Pharmaceuticals, a subsidiary of Astellas US, LLC,~~UFRF and Penn for rights to ~~particular anti-PDGF aptamers, including Fovista,~~IC-100, the Company is obligated to ~~pay~~make payments to ~~OSI Pharmaceuticals future one-time payments~~UFRF, for the benefit of ~~$12.0~~Penn and UFRF (together, the "Licensors"), of up to an aggregate of $23.5 million inif the ~~aggregate upon~~Company achieves specified clinical, marketing approval inand reimbursement approval milestones with respect to a licensed product and up to an aggregate of an additional $70.0 million if the ~~United States and the European Union of~~Company achieves specified commercial sales milestones with respect to a ~~covered anti-PDGF~~licensed product. The Company is also obligated to pay ~~to OSI Pharmaceuticals a royalty at~~UFRF, for the benefit of the Licensors, a low single-digit percentage of net sales of ~~any covered anti-PDGF product~~licensed products. The Company is also obligated to pay UFRF, for the benefit of the Licensors, a double-digit percentage of specified non-royalty payments the Company ~~successfully commercializes.~~

~~Under~~may receive from any third-party sublicensee of the licensed patent rights. Further, if the Company receives a ~~license agreement~~rare pediatric disease priority review voucher from the U.S. Food and Drug Administration ("FDA") in connection with ~~Archemix Corp., or Archemix,~~obtaining marketing approval for a licensed product and the Company subsequently uses such priority review voucher in connection with a different product candidate, the Company will be obligated to pay UFRF, for the benefit of the Licensors, aggregate payments in the low double-digit millions of dollars based on certain approval and commercial sales milestones with respect to ~~pharmaceutical products comprised~~such other product candidate. In addition, if the Company sells such a priority review voucher to a third party, the Company will be obligated to pay UFRF, for the benefit of ~~or derived~~the Licensors, a low double-digit percentage of any consideration received from ~~any anti-PDGF aptamer,~~such third party in connection with such sale.

HtrA1 Inhibitors - Former Equityholders of Inception 4

Under the agreement and plan of merger pursuant to which the Company acquired Inception 4 (the "Inception 4 Merger Agreement"), the Company is obligated to make ~~future~~ payments to ~~Archemix~~the former equityholders of Inception 4 of up to an aggregate of ~~$14.0~~$105 million, subject to the terms and conditions of the Inception 4 Merger Agreement, if the Company achieves certain specified clinical and regulatory milestones with respect to ~~Fovista, up~~a product candidate from its HtrA1 inhibitor program, with $45 million of such potential payments relating to ~~an aggregate~~GA and $60 million of ~~$3.0 million if~~such potential payments relating to wet AMD. Under the Inception 4 Merger Agreement, the Company ~~achieves specified~~does not owe any commercial milestones or royalties based on net sales. The future milestone payments will be payable in the form of shares of the Company's common stock, calculated based on the price of its common stock over a five-trading day period preceding the achievement of the relevant milestone, unless and until the issuance of such shares would, together with ~~respect to Fovista and, for each~~all other ~~anti-PDGF aptamer product that it may develop under~~shares issued in connection with the ~~agreement, up to~~acquisition, exceed an ~~aggregate~~overall maximum limit of approximately ~~$18.8~~7.2 million ifshares, which is equal to 19.9% of the ~~Company achieves specified clinical~~number of issued and ~~regulatory milestones and up to an aggregate~~outstanding shares of ~~$3.0 million if~~ the ~~Company achieves specified commercial milestones. No royalties are payable to Archemix under this license agreement.~~

~~Under a license, manufacturing and supply agreement with Nektar for specified pegylation reagents used to manufacture Fovista,~~Company's common stock as of the ~~Company was obligated to make future payments to Nektar~~close of ~~up to an aggregate of $6.5 million if~~business on the Company achieved specified clinical and regulatory milestones, and an additional payment of $3.0 million if the Company achieved a specified commercial milestone with respect to Fovista. The Company was obligated to pay Nektar tiered royalties at low to mid-single-digit percentages of net sales of any licensed product the Company successfully commercializes, with the royalty percentage determined by the Company’s level of licensed product sales, the extent of patent coverage for the licensed product and whether the Company has granted a third-party commercialization rightsbusiness day prior to the ~~licensed product. In June 2014,~~closing date of the ~~Company paid Nektar~~Inception 4 acquisition, and will be payable in cash thereafter. The Inception 4 Merger Agreement also includes customary indemnification obligations to the former equityholders of Inception 4, including for breaches of the representations and warranties, covenants

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~~$19.8 million in connection with its entry into the Novartis Agreement. On October 27, 2017, Nektar~~ and agreements of the Company ~~agreed to terminate~~and its subsidiaries (other than Inception 4) in the ~~license, manufacturing and supply agreement effective immediately. Neither party incurred any additional costs in connection with the termination of the license, manufacturing and supply agreement.~~

Under the Novo Agreement, with respect to Fovista, the Company will be obligated to pay Novo A/S a mid-single-digit percentage royalty based on worldwide sales of Fovista. See "Note 6—Financing Agreement with Novo A/S" above for further information about NovoInception 4 Merger Agreement.

Employment Contracts

The Company also has letter agreements with certain employees that require the funding of a specific level of payments if certain events, such as a termination of employment in connection with a change in control or termination of employment by the employee for good reason or by the Company without cause, occur.

Contract Service Providers

In addition, in the course of normal business operations, the Company has agreements with contract service providers to assist in the performance of the Company’s research and development and manufacturing activities. Expenditures to CROs and ~~CMOs~~CDMOs represent significant costs in preclinical and clinical development. Subject to required notice periods and the Company’s obligations under binding purchase orders and any cancellation fees that the Company may be obligated to pay, the Company can elect to discontinue the work under these agreements at any time.

Legal Proceedings

On January 11, 2017, a putative class action lawsuit was filed against the Company and certain of its current and former executive officers in the United States District Court for the Southern District of New York, captioned Frank Micholle v. Ophthotech Corporation, et al., No. 1:17-cv-00210. The complaint purports to be brought on behalf of shareholders who purchased the Company's common stock between May 11, 2015 and December 12, 2016. The complaint generally alleges that the Company and certain of its officers violated Sections 10(b) and/or 20(a) of the Securities Exchange Act of 1934 and Rule 10b-5 promulgated thereunder by making allegedly false and/or misleading statements concerning the prospects of the Company's Phase 3 trials for Fovista in combination with anti-VEGF drugs for the treatment of wet AMD. The complaint seeks equitable and/or injunctive relief, unspecified damages, attorneys’ fees, and other costs.

On March 9, 2017, a ~~second~~related putative class action lawsuit was filed against the Company and the same group of its current and former executive officers in the United States District Court for the Southern District of New York, captioned Wasson v. Ophthotech Corporation, et al., No. 1:17-cv-01758. These cases were consolidated on March 13, 2018. On June 4, 2018, the lead plaintiff filed a consolidated amended complaint (the “CAC”). The ~~complaint~~CAC purports to be brought on behalf of shareholders who purchased the Company’s common stock between ~~May 11,~~March 2, 2015 and December 9,12, 2016. The ~~allegations made~~CAC generally alleges that the Company and certain of its officers violated Sections 10(b) and/or 20(a) of the Securities Exchange Act of 1934 and Rule 10b-5 promulgated thereunder by making allegedly false and/or misleading statements concerning the results of the Company’s Phase 2b trial and the prospects of the Company’s Phase 3 trials for Fovista in combination with anti-VEGF agents for the treatment of wet AMD. The CAC seeks unspecified damages, attorneys’ fees, and other costs. The Company and individual defendants filed a motion to dismiss the CAC on July 27, 2018. That motion is fully briefed.

On February 7, 2018, a shareholder derivative action was filed against the members of the Company’s Board of Directors in the New York Supreme Court Commercial Division, captioned Cano v. Guyer, et al., No. 650601/2018. The complaint alleges that the defendants breached their fiduciary duties to the Company by adopting a compensation plan that overcompensates the non-employee members of the Company's board relative to boards of companies of comparable market capitalization and size. The complaint also alleges that the defendants were unjustly enriched as a result of the alleged conduct. The complaint purports to seek unspecified damages, on behalf of the Company, attorneys’ fees, and other costs, as well as an order directing the Company to reform and improve its corporate governance and internal procedures to comply with applicable laws. The Company filed a motion to dismiss this case on May 14, 2018. On June 4, 2018, the plaintiff filed an amended complaint. On June 25, 2018, the Company filed a renewed motion to dismiss this case. On December 3, 2018, the parties filed a stipulation of settlement that contemplates that the Company will adopt certain compensation-related governance reforms and does not obligate the defendants or the Company to pay any monetary damages. The court approved the settlement at a hearing on March 12, 2019. As part of the settlement, the Company agreed to pay approximately $300,000 in fees and costs to plaintiff's counsel. As contemplated by the settlement, the Company's board of directors adopted certain compensation-related governance reforms, including a non-employee director compensation policy, which is being proposed for approval by the Company's stockholders at its 2019 annual meeting.

On August 31, 2018, a shareholder derivative action was filed against current and former members of the Company's Board of Directors and certain current and former officers of the Company in the United States District Court for the Southern District of New York, captioned Luis Pacheco v. David R. Guyer,et al., Case No. 1:18-cv-07999. The complaint, which is based substantially on the facts alleged in the CAC, alleges that the defendants breached their fiduciary duties to the Company and wasted the Company's corporate assets by failing to oversee the Company's business, and also alleges that the defendants were unjustly enriched as a result of the alleged conduct, including through receipt of bonuses, stock options and similar compensation from the Company, and through sales of the Company's stock between March 2, 2015 and December 12, 2016. The complaint purports to seek unspecified damages on the Company's behalf, attorneys’ fees, and other costs, as well as an order directing the Company to reform and improve its corporate governance and internal procedures to comply with applicable laws, including submitting certain proposed amendments to the Company's corporate charter, bylaws and corporate governance policies for vote by the Company's stockholders. On December 14, 2018, the Company filed a motion to dismiss the complaint. That motion is fully briefed.

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On October 16, 2018, the Company’s board of directors received a shareholder demand to investigate and commence legal proceedings against certain members of the Company’s board of directors. The demand alleges facts that are substantially similar to ~~those made~~the facts alleged in the ~~Micholle complaint. Putative lead plaintiffs~~CAC and the Pacheco complaint and asserts claims that are substantially similar to the claims asserted in the ~~Micholle action have moved~~Pacheco complaint. On January 30, 2019, the Company’s board of directors received a second shareholder demand from a different shareholder to ~~consolidate~~investigate and commence legal proceedings against certain current and former members of the ~~Micholle and Wasson actions.~~

Company’s board of directors based on allegations that are substantially similar to the allegations contained in the first demand letter.

The Company denies any and all allegations of wrongdoing and intends to vigorously defend against these lawsuits. The Company is unable, however, to predict the outcome of these matters at this time. Moreover, any conclusion of these matters in a manner adverse to the Company and for which it incurs substantial costs or damages not covered by the Company's directors’ and officers’ liability insurance would have a material adverse effect on its financial condition and business. In addition, the litigation could adversely impact the Company's reputation and divert management’s attention and resources from other priorities, including the execution of its business ~~plans~~plan and strategies that are important to the Company's ability to grow its business, any of which could have a material adverse effect on the Company's business.

10. Subsequent Event

IC-200: BEST1 License Agreement

On May 30, 2017, a shareholder derivative action was filed against the members of the Company’s Board of Directors in the United States District Court for the Southern District of New York, captioned Etelmendorf v. Bolte, et al., No. 1:17-cv-04042. The complaint alleges that defendants breached their fiduciary duties toApril 11, 2019, the Company entered into an exclusive global license agreement (the "BEST1 License Agreement") with Penn and UFRF. The Company entered into the BEST1 License Agreement by ~~causing or permitting~~exercising its exclusive option rights under an option agreement that the Company previously entered into with the Licensors in October 2018. Under the BEST1 License Agreement, the Licensors granted the Company a worldwide, exclusive license under specified patent rights and specified know-how and a worldwide, non-exclusive license under other specified know-how to ~~make allegedly false and/or misleading statements concerning the prospects of the Company’s Phase 3 trials for Fovista in combination with anti-VEGF drugs~~research, develop, manufacture and commercialize certain AAV gene therapy products, including IC-200, for the treatment of wet AMD, and by approving certain executive compensation. The complaint also alleges that defendants were unjustly enriched as a result of the alleged conduct. The complaint purports to seek unspecified damages on behalf of the Company, as well as an order directing the Company to reform and comply with its governance obligations, attorneys’ fees,Best disease and other ~~costs. On October 17, 2017, the plaintiff filed a notice of voluntary dismissal without prejudice for this action.~~

~~12. Restructuring Activities~~bestrophinopathies.

In ~~December 2016,~~May 2019, the Company ~~announced its intention~~paid Penn, for the benefit of the Licensors, a $0.2 million upfront license issuance fee, which the Company recorded as a research and development expense, and paid UFRF accrued patent prosecution expenses of approximately $18 thousand, which the Company recorded as a general and administrative expense. The Company has also agreed to ~~implement a reduction~~pay Penn, for the benefit of the Licensors, an annual license maintenance fee in ~~personnel to focus~~the low double-digit thousands of dollars, which fee will be payable on an ~~updated business plan.~~annual basis until the first commercial sale of a licensed product. In ~~January 2017,~~addition, the ~~Board~~Company has agreed to pay Penn, for the benefit of ~~Directors approved~~the Licensors, a ~~plan~~one-time patent grant fee in the low triple-digit thousands of dollars, upon the issuance of a U.S. patent that claims inventions disclosed in the licensed patent rights or know-how or inventions generated under certain related sponsored research agreements with Penn or UFRF, and that is exclusively licensed to ~~implement~~the Company. Furthermore, the Company has agreed to reimburse Penn and UFRF for the costs and expenses of patent prosecution and maintenance related to the licensed patent rights.

The Company has further agreed to pay Penn, for the benefit of the Licensors, up to an aggregate of $15.7 million if the Company achieves specified clinical, marketing approval and reimbursement approval milestones with respect to one licensed product, and up to an aggregate of an additional $3.1 million if the Company achieves these same milestones with respect to a ~~reduction~~different licensed product. In addition, the Company has agreed to pay Penn, for the benefit of the Licensors, up to an aggregate of $48.0 million if the Company achieves specified commercial sales milestones with respect to one licensed product, and up to an aggregate of an additional $9.6 million if the Company achieves these same milestones with respect to a different licensed product.

The Company is also obligated to pay Penn, for the benefit of the Licensors, royalties at a low single-digit percentage of net sales of licensed products. Such royalties are subject to customary deductions, credits, and reductions for lack of patent coverage and loss of regulatory exclusivity. In addition, such royalties with respect to any licensed product in ~~personnel involving~~any country may be offset by a specified portion of any royalty payments actually paid by the Company with respect to such licensed product in such country under third-party licenses to patent rights or other intellectual property rights that are necessary to research, develop, manufacture and commercialize the licensed product in such country. The Company’s obligation to pay royalties under the BEST1 License Agreement will continue on a licensed product-by-licensed product and country-by-country basis until the latest of: (a) the expiration of the last-to-expire licensed patent rights covering the sale of the applicable licensed product in the country of sale, (b) the expiration of regulatory exclusivity covering the applicable licensed product in the country of sale and (c) 10 years from the first commercial sale of the applicable licensed product in the country of sale. Beginning on the earlier of (i) the calendar year following the first commercial sale of a licensed product and (ii) calendar year

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~~approximately 80%~~2032, the Company is also obligated to pay certain minimum royalties, not to exceed an amount in the mid tens of thousands of dollars on an annual basis, which minimum royalties are creditable against the Company’s royalty obligation with respect to net sales of licensed products due in the year the minimum royalty is paid.

If the Company or any of its affiliates sublicense any of the ~~Company’s workforce~~licensed patent rights to a third party, the Company will be obligated to pay Penn, for the benefit of the Licensors, a high single-digit to a mid-teen percentage of the consideration received in exchange for such sublicense, with the applicable percentage based onupon the ~~number~~stage of ~~employees~~development of the sublicensed product at the time the ~~plan was approved. During~~Company or the ~~first nine months of 2017,~~applicable affiliate enters into the ~~Company's workforce has been reduced by 112 employees~~sublicense.

If the Company receives a rare pediatric disease priority review voucher from the FDA in connection with obtaining marketing approval for a licensed product and the ~~reduction~~Company subsequently uses such priority review voucher in ~~personnel and through natural attrition. The Company expects to complete the reduction in personnel during the fourth quarter of 2017. In~~ connection with ~~such reduction in personnel,~~a different product candidate outside the Company estimates that it will incur approximately $13.3 million of pre-tax charges through the third quarter of 2017, of which approximately $12.4 million in the aggregate is expected to result in cash expenditures. These pre-tax charges relate to (a) expected severance, stock compensation and other employee costs of approximately $11.2 million and (b) expected lease termination costs of approximately $2.1 million. As of September 30, 2017, the Company's cash expenditures related to such reduction in personnel totaled $8.7 million.

In connection with the reduction in personnel, the Company recognized approximately $1.4 million and $11.9 million of severance, stock compensation and other employee costs for the three and nine months ended ~~September 30, 2017~~, of which $0.9 million and $6.8 million were recorded in "Research and development" expense and $0.5 million and $5.1 million were recorded in "General and administrative" expense in the Company's Statements of Operations.

~~As of~~ ~~September 30, 2017~~, the Company's accrual balance for severance and benefit costs was $2.3 million which was recorded in "Accounts payable and accrued expenses" in the Company's Balance Sheet. The severance and other employee cost accruals as of ~~September 30, 2017~~ ~~are expected to be paid through to the first half of 2018.~~

~~The following is a reconciliation~~scope of the ~~severance-related accrual activity for the nine months ended~~ ~~September 30, 2017~~:

Accrued Severance and Other Employee Costs
Beginning Balance $ —
Accrued restructuring expenses 11,076
Payments (8,727 )
Ending Balance $ 2,349

In ~~January 2017, the Company issued a notice of termination under the Lease~~BEST1 License Agreement, dated as of September 30, 2007, between the Company and One Penn Plaza LLC, as previously supplemented and amended (as so supplemented and amended, the “Lease”) for office space at One Penn Plaza in New York, New York. The termination of the Lease triggered an early termination payment by the Company of approximately $0.9 million and will be effective in January 2018, through which time the Company will be ~~responsible~~obligated to pay Penn, for ~~paying continuing rental fees, as well as taxes, operating expenses~~the benefit of the Licensors, aggregate payments in the low double-digit millions of dollars based on certain approval and ~~utility and~~commercial sales milestones with respect to such other ~~charges related to the leased premises. On November 1, 2017,~~product candidate. In addition, if the Company ~~and One Penn Plaza LLC executed~~sells such a ~~further amendment~~priority review voucher to ~~the Lease. See "~~—~~Note 13~~—~~Subsequent Events" for~~ a ~~description of the further lease amendment. Payments under the further lease amendment will not constitute restructuring charges.~~

On January 26, 2017, the Company issued a notice of termination under the Sublease Agreement between the Company and Otsuka America Pharmaceutical, Inc. (the “Sublease”) for office space at One University Square, Princeton, New Jersey. The termination of the Sublease triggered an early termination payment by the Company of approximately $1.2 million and will be effective in February 2018, through which timethird party, the Company will be ~~responsible~~obligated to pay Penn, for ~~paying continuing rental fees, as well as taxes, operating expenses and utility and other charges related to~~ the ~~subleased premises.~~

On January 26, 2017, the Company issued a notice of termination under its Office Lease Agreement between the Company and PSN Partners, L.P. (the “Office Lease”) for office space in Palmer Square in Princeton, New Jersey. The terminationbenefit of the ~~Office Lease did not trigger~~Licensors, a high single-digit percentage of any ~~early termination payment and is effective October 2017.~~

~~During January 2017, the Company made the early termination payments as described above and recognized $2.1 million of additional facilities costs which were recorded~~consideration received from such third party in ~~"General and administrative" expense in the Company's Statements of Operations.~~connection with such sale.

~~13. Subsequent Events~~

~~On October 24, 2017, Novartis delivered to the Company a notice of termination of the Novartis Agreement dated October 23, 2017. The termination notice was effective immediately.~~

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On October 27, 2017, Nektar and the Company agreed to terminate the License, Manufacturing and Supply Agreement with respect to PEG reagent used to manufacture Fovista. The termination was effective immediately.

On November 1, 2017, the Company entered into a fifth amendment of lease (the “Fifth Lease Amendment”) with One Penn Plaza LLC, as landlord, amending, effective as of October 1, 2017, the Lease Agreement, dated as of September 30, 2007, between the Company and One Penn Plaza LLC, as previously supplemented and amended (as so supplemented and amended, the “Lease”). The Fifth Lease Amendment provides for a different, smaller premises to be made available to the Company under the Lease at One Penn Plaza, New York, NY, resulting in total office space available under the Lease of approximately 13,500 square feet. The Company intends to use the office space for corporate and clinical operations. The new office space will be available to the Company following the completion of construction being performed by the landlord, which is expected to be completed prior to the end of January 2018. Notwithstanding the Company's prior termination notice under the Lease, the Lease is now scheduled to expire at the end of 2018. The incremental rental fees, which includes utilities costs, over the extended term of the Lease from January through December 2018 are expected to be approximately $650 thousand. The Company is also liable for taxes, and other charges related to the leased premises. The Company previously provided the landlord with a letter of credit in an amount of approximately $138 thousand to secure the Company’s obligations under the Lease.

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

The following discussion and analysis of our financial condition and results of operations should be read ~~in conjunction~~together with our financial statements and ~~the~~related notes ~~to those financial statements~~ appearing elsewhere in this Quarterly Report on Form 10-Q and the audited ~~consolidated~~ financial statements and related notes ~~thereto~~ and management’s discussion and analysis of financial condition and results of operations for the year ended December 31, ~~2016~~2018 included in our Annual Report on Form 10-K filed with the Securities and Exchange Commission on February 28, ~~2017. This~~2019. Some of the information contained in this discussion ~~contains~~and analysis or set forth elsewhere in this Quarterly Report on Form 10-Q, including information with respect to our plans and strategy for our business and related financing, includes forward-looking statements that involve ~~significant~~ risks and ~~uncertainties. As a result of many factors, such as those set forth in Part II, Item 1A. (Risk Factors)~~uncertainties and should be read together with the "Risk Factors" section of this Quarterly Report on Form 10-Q ~~our~~for a discussion of important factors that could cause actual results ~~may~~to differ materially from ~~those anticipated~~the results described in ~~these~~or implied by the forward-looking ~~statements.~~

statements contained in the following discussion and analysis.

Overview

~~Updated Business Plan~~

We are a science-driven biopharmaceutical company ~~specializing in the development of novel therapeutics to treat ophthalmic diseases,~~ with a focus on ~~age-related~~discovering and developing novel gene therapy solutions to treat orphan inherited retinal diseases, or IRDs, with unmet medical needs. We recently changed our name from Ophthotech Corporation to IVERIC bio, Inc. to reflect the transition of our business to focus principally on gene therapies. We believe that gene therapy as a treatment modality, especially gene therapies using adeno-associated virus, or AAV, for gene delivery, holds tremendous promise for retinal diseases. We ~~currently have two product candidates in development,~~also continue to develop our therapeutic programs, including our ongoing clinical trials for our C5 complement inhibitor Zimura® (avacincaptad pegol), for an ~~anti-complement factor C5 aptamer,~~age-related retinal disease and ~~Fovista® (pegpleranib),~~for an ~~anti-platelet derived growth factor,~~orphan IRD. If data from our Zimura clinical trials are positive, we may seek partnering opportunities for further clinical development of Zimura.

Our team has significant drug development experience in retinal diseases, including designing and executing investigational new drug, or ~~PDGF, aptamer. Prior~~IND, -enabling studies and clinical trials, and we are continuing to ~~2017,~~build our ~~primary focus was on developing Fovista~~internal and ~~Zimura~~external capabilities, especially in the preclinical development, clinical development and manufacture of gene therapies. We also have deep relationships with global ophthalmology thought leaders, including those at a number of leading academic research institutions with which we have developed collaborative relationships, and an extensive network of ophthalmic clinical trial sites. We will seek to leverage these existing relationships as we prepare for ~~various types~~potential clinical trials for our gene therapy product candidates. We believe that the combination of ~~age-related macular degeneration,~~these factors provide us a competitive advantage in retinal drug development.

Our gene therapy portfolio consists of several ongoing research and preclinical development programs that use AAV for gene delivery. These AAV gene therapy programs are targeting the following orphan IRDs:

rhodopsin-mediated autosomal dominant retinitis pigmentosa, or ~~AMD,~~RHO-adRP, which is ~~a disorder~~characterized by progressive and severe bilateral loss of vision leading to blindness;

Best vitelliform macular dystrophy, or Best disease, which is characterized by bilateral egg yolk-like lesions in the central portion of the retina, ~~known~~referred to as the macula, ~~that~~which, over time, progress to atrophy and loss of vision, and potentially other diseases associated with mutations in the Best1 gene, which we refer to as bestrophinopathies;

Leber congenital amaurosis type 10, or LCA10, which is characterized by severe bilateral loss of vision at or soon after birth; and

autosomal recessive Stargardt disease, or STGD1, which is characterized by progressive damage to the macula and retina, leading to loss of vision in children and young adults.

Our therapeutics portfolio consists of Zimura and our program of High temperature requirement A serine peptidase 1 protein, or HtrA1, inhibitors. We have Phase 2b clinical trials ongoing evaluating Zimura for the treatment of:

geographic atrophy, or GA, which is a late-stage form of dry age-related macular degeneration, or AMD, characterized by retinal cell death and degeneration of tissue in the macula, and which may result in ~~blindness. In December 2016, we announced that two~~loss of ~~our three pivotal Phase 3 clinical trials for Fovista~~vision; and

autosomal recessive Stargardt disease.

We previously also evaluated Zimura in combination with ~~the~~Lucentis® (ranibizumab), an anti-vascular endothelial growth factor, or anti-VEGF, ~~drug Lucentis® (ranibizumab)~~agent for the treatment of wet AMD, for which we completed a Phase 2a clinical trial, which we refer to as the ~~OPH1002 and OPH1003 trials, failed to meet their primary endpoint. In August 2017, we announced that~~OPH2007 trial, during the ~~third pivotal Phase 3 clinical trial for Fovista in combination with the anti-VEGF drugs Eylea® (aflibercept) or Avastin® (bevacizumab) for the treatment~~fourth quarter of ~~wet AMD, which we refer to as the OPH1004 trial, failed to meet its primary endpoint.~~2018. We ~~are in the process of winding down the OPH1004 Fovista trial and~~do not currently have ~~no future~~ plans to develop ~~Fovista~~Zimura further in wet ~~AMD and only very limited Fovista development activity outside of wet~~ AMD. In early 2017 we announced that we had engaged a financial advisor to assist us in reviewing our strategic alternatives, including identifying potential business development opportunities. Also beginning in early 2017, we undertook a reassessment of our development plans for Zimura and Fovista, which included an evaluation of the scientific rationale for potentially developing these product candidates in one or more other ophthalmic indications for which there is a high unmet need. In July 2017, we announced that we are pursuing a strategy to leverage our clinical experience and retina expertise to identify and develop therapies to treat multiple ophthalmic orphan diseases for which there are limited or no treatment options available. We believe that there are advantages of orphan drug development, including regulatory exclusivity, the potential for smaller clinical trials and the potential for an accelerated development timeline for orphan retinal indications. In parallel, we are continuing our on-going Zimura programs in age-related retinal diseases. We believe that by leveraging our ophthalmic expertise and by focusing on orphan eye diseases together with our on-going Zimura programs in age-related retinal diseases, we will have multiple potential opportunities to bring ophthalmic therapeutics to market. We also are continuing our business development efforts to identify and potentially obtain rights to additional products, product candidates and technologies that would complement our strategic goals as well as other compelling ophthalmology opportunities.

Our

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~~Zimura~~HtrA1 inhibitor program, which we are developing for GA secondary to dry AMD and potentially other age-related retinal diseases, is in the preclinical stage of development.

Gene Therapy Research and Development Programs

~~As part~~IC-100: RHO-adRP Product Candidate

We are pursuing the preclinical development of IC-100, our ~~strategic review process during 2017, we reassessed our development plans for our~~novel AAV gene therapy product candidate ~~Zimura.~~for the treatment of RHO-adRP, to which we acquired exclusive development and commercialization rights through a June 2018 license agreement with the University of Florida Research Foundation, or UFRF, and the University of Pennsylvania, or Penn. We ~~applied~~and Penn are conducting additional preclinical studies of IC-100 and a natural history study of RHO-adRP patients. In parallel, we have engaged a gene therapy contract development and manufacturing organization, or CDMO, as the ~~same rigor~~manufacturer for preclinical and Phase 1/2 clinical supply of IC-100 and have commenced manufacturing and other IND-enabling activities. Based on current timelines and subject to regulatory review, we expect to initiate a Phase 1/2 clinical trial for IC-100 during 2020.

IC-200: Product Candidate for Bestrophinopathies

We are pursuing the preclinical development of IC-200, our novel AAV gene therapy product candidate for the treatment of Best disease and other bestrophinopathies. During the fourth quarter of 2018, we entered into an option agreement for this program and commenced development activities. In April 2019, we acquired exclusive development and commercialization rights to this program by exercising our option and entering into a license agreement with Penn and UFRF. We and Penn are conducting additional preclinical studies of IC-200 and natural history studies of patients with bestrophinopathies. In parallel, we have engaged a gene therapy CDMO as the manufacturer for pre-clinical and Phase 1/2 clinical supply of IC-200 and have commenced manufacturing and other IND-enabling activities. Based on current timelines and subject to regulatory review, we expect to initiate a Phase 1/2 clinical trial for IC-200 during the first half of 2021.

University of Massachusetts Medical School Research (LCA10 and STGD1; Gene Delivery Methods)

We are funding three sponsored research programs at the University of Massachusetts Medical School, or UMMS. Two of these programs seek to utilize a "minigene" approach to create AAV gene therapy product candidates targeting LCA10 and STGD1. AAV vectors are generally limited as a delivery vehicle by the size of their genetic cargo, which is restricted to approximately 4,700 base pairs of genetic code. The use of "minigenes" seeks to deliver a smaller but still functional form of a larger gene packaged into a standard-size AAV delivery vector. The third program is evaluating various AAV gene delivery methods for potential application in ~~reassessing~~the eye. We receive results from these sponsored research programs as they become available. UMMS has granted us an option to obtain an exclusive license to any patents or patent applications that result from these sponsored research programs.

Therapeutic Development Programs

Although we are principally focused on gene therapies, we continue to believe therapeutics will serve an important role in drug development for retinal diseases, particularly as treatments with novel mechanisms of action are developed and brought to market and as the long-term effects of these treatments continue to be understood.

Zimura Clinical Programs

Zimura, our ~~development plans~~C5 complement inhibitor, is a chemically-synthesized, pegylated RNA aptamer. We currently have two clinical trials for Zimura as we used in performing diligence on third party opportunities considered as part of our strategic review process. Our Zimura reassessment included an extensive review of scientific literature regarding the role of complement in ophthalmic diseases. Upon the conclusion of this reassessment, we determined to accelerate our development of Zimura in additional ophthalmic indications and to make certain modifications to our existing programs in age-related retinal diseases. Our ongoing and plannedongoing. These clinical ~~studies for Zimura, all of which~~trials are designed to obtain data to guide potential future development efforts and are ~~as follows:~~not intended to be pivotal studies. The following is a brief description of our ongoing trials and their current status:

OPH2003 (geographic atrophy (GA) secondary to dry AMD): an ongoing, randomized, ~~double‑masked,~~double-masked, sham controlled, multi-center Phase 2b clinical trial ~~to evaluate~~evaluating the safety and efficacy of Zimura monotherapy in patients with ~~geographic atrophy, or~~ GA secondary to dry AMD. Geographic atrophy, the end stage of dry AMD, is a disease signified by retinal cell death and degeneration of retinal tissue. Following the recent announcements of competitors' conflicting top-line results from two clinical trials assessing the role of two different types of complement inhibitorsWe completed enrollment for ~~the treatment of GA, we modified our ongoing Phase 2/3~~this clinical trial ~~of Zimura monotherapy~~ in GA. One competitor, developing an inhibitor directed towards the alternative complement pathway, is in Phase 3 trials, the first of which did not meet its primary efficacy endpoint and the second of which is expected to have initial top-line data available before the end of 2017. The other competitor, developing an inhibitor blocking all three complement pathways, has provided data from an ongoing Phase 2b trial that met its primary efficacy endpoint. Zimura inhibits complement factor C5, which is further downstream following convergence of all three complement pathways. We had originally planned to enroll 300 patients in an initial stage of the OPH2003 trial, with an interim analysis scheduled at 18 months, and to potentially enroll up to an additional 600 patients thereafter. We have modified the trial to accelerate the timeline to obtain top-line data by reducing the number of patients we plan to enroll to approximately 200 patients and by shortening the time point for evaluating the primary efficacy endpoint to 12 months,October 2018 with a ~~treatment duration~~total of ~~18 months.~~286 patients enrolled. We have also expanded the number of sites in the United States and outside the United States to expedite enrollment. The primary efficacy endpoint is an anatomic endpoint, the mean change in rate of GA at 12 months, as measured by fundus autofluorescence. The modified trial design incorporates patientsexpect that were already enrolled in the trial prior to the modifications and includes Zimura dosing regimens not previously studied. We submitted the amended clinical trial protocol to the U.S. Food and Drug Administration, or FDA, early in the fourth quarter of 2017. Based on our anticipated enrollment rate, we expect initial, top-line data from this clinical trial towill be available during the ~~second half~~fourth quarter of ~~2019;~~2019.

OPH2007 (wet AMD): an ongoing dose-ranging, open-label, multi-center Phase 2a clinical trial of Zimura in combination with Lucentis for the treatment of wet AMD in patients who have not previously been treated with anti-VEGF drugs, referred to as treatment-naïve patients. We initiated this trial during the third quarter of 2017. We plan to enroll approximately 60 patients in this trial and to evaluate patient data at the 6-month time point. As this is a Phase 2a trial, we plan to evaluate all available safety measures including vision outcomes. The design for the trial includes Zimura dosing regimens not previously studied. Based on our anticipated enrollment rate, we expect initial top-line data from this trial to be available by the end of 2018. Prior to commencing this trial, we ceased enrolling patients in OPH2004, a prior open-label Phase 2a clinical trial of Zimura in wet AMD patients who had been previously treated with anti-VEGF drugs, referred to as treatment-experienced patients;

OPH2005 (autosomal recessive Stargardt disease (STGD1)): ~~a planned~~an ongoing, randomized, double-masked, sham controlled, multi-center Phase 2b clinical trial evaluating the safety and efficacy of Zimura monotherapy for the treatment of ~~autosomal recessive Stargardt disease, referred to as~~ STGD1. ~~STGD1 is an inherited orphan retinal disease causing vision loss during childhood or adolescence~~We completed enrollment for ~~which currently no FDA or EMA approved treatment are available and it remains a major unmet medical need. We plan to enroll approximately 120 patients in~~ this trial and to evaluate the primary efficacy endpoint at 18-months. The primary efficacy endpoint is an anatomic endpoint, mean rate of change in the area of ellipsoid zone defect, as measured by spectral domain optical coherence tomography, or SD-OCT. Scientific literature correlates ellipsoid zone defect with visual dysfunction. The design of the trial, which is scheduled to initiate before the end of 2017, includes Zimura dosing regimens that have not been studied prior to the modified OPH2003 and OPH2007 trials. We previously engaged the Foundation Fighting Blindness to provide us with data from the Foundation's publicly available ProgStar study, the largest natural history study on STGD1 disease to date. We have used this natural history data as a resource to assist in the design of the OPH2005 trial. Based on our anticipated enrollment rate, we expect initial top-line data from this trial to be available during 2020;

~~OPH2006 (IPCV): a planned open-label Phase 2a~~ clinical trial in February 2019 with a total of Zimura in combination with Eylea for the treatment of idiopathic polypoidal choroidal vasculopathy, or IPCV, an age-related retinal disease involving the choroidal vasculature characterized by the presence of polypoidal lesions, which leads to vision loss. We expect to enroll95 patients

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approximately 20 patients and plan to evaluate patient data at the 9-month time point. As this is a Phase 2a trial, we plan to evaluate all available safety measures including vision outcomes. This trial is scheduled to initiate by the end of 2017. Based on our anticipated enrollment rate, weenrolled. We expect that initial, top-line data tofrom this clinical trial will be available ~~from this trial~~ during the second half of ~~2019; and~~2020.

~~a planned open-label Phase 2a clinical trial~~HtrA1 Inhibitor Program

We are pursuing the preclinical development of ~~Zimura monotherapy~~certain HtrA1 inhibitors, to which we acquired rights through our October 2018 acquisition of Inception 4, Inc., or Inception 4, for the treatment of ~~non-infections intermediate~~GA secondary to dry AMD. Our HtrA1 inhibitor program includes a number of lead small molecule compounds that show high affinity and ~~posterior uveitis,~~specificity for HtrA1 when tested, as well as a ~~rare inflammatory disease~~number of backup compounds. We are pursuing formulation development studies with the goal of identifying a formulation for intravitreal application in the eye. If we are successful in identifying and formulating a product candidate from this program, we plan to initiate IND-enabling activities for the selected product candidate. Based on current timelines and subject to successful completion of preclinical development, we are targeting submission of an IND to the U.S. Food and Drug Administration, or FDA, for a product candidate from this program by late 2020.

Research and Development Pipeline

The following table summarizes the current status of our ongoing research and development programs:

Business Development Activities

Since early 2017, we have been pursuing a business development strategy to evaluate available technologies to treat opthalmic diseases, particularly those in the back of the eye, ~~is scheduled~~and to ~~be initiated during 2018.~~

~~Given that we have limited data regarding the effect of Zimura in GA, we determined the size of the OPH2003 trial based on our best estimates of the size of trial required~~explore opportunities to demonstrate a potential clinical benefit for Zimura. This estimate is based on our assumptions regarding the potential performance of Zimura in this indication based in part on available third-party clinical data. In addition, given that we have no clinical data regarding the effect of Zimura in STGD1, we determined the size of the OPH2005 trial based on the number of patients with STGD1 that we believe could potentially be enrolled within a reasonable period of time. Based on the actual enrollment rate during the trial, this number may be increased or decreased. As STGD1 is an orphan indication, to our knowledge there is no natural history data currently available regarding the variability of the planned primary efficacy endpoint in the STGD1 patient population we plan to enroll in this trial. Based on the information above, these trials could be underpowered to demonstrate a potential clinical benefit for Zimura in these indications.

~~On-going business development activities~~

In early 2017, we engaged Leerink Partners, a financial advisor, and initiated a plan to review our strategic alternatives in order to maximize shareholder value following the failure of two of our three pivotal Fovista trials. Without limiting any option, the principal focus of this plan, based on our deep expertise and experience in ophthalmology, has been to actively explore obtainingobtain rights to additional products and product candidates employing these technologies. As we evaluated numerous potential opportunities, we have come to believe that gene therapy is a promising treatment modality for retina diseases for which there are significant unmet medical needs. Our efforts have resulted in the expansion of our research and development pipeline and the transition of our company to focus principally on gene therapy. We initiated our gene therapy sponsored research programs with UMMS in February 2018, in-licensed IC-100 in June 2018 and IC-200 in April 2019. We also acquired Inception 4 in October 2018. We expect to continue to evaluate, on a selective basis, opportunities to potentially obtain rights to additional gene therapy product candidates and technologies for retinal diseases. We intend to ~~treat ophthalmic diseases, particularly those of~~continue to focus on opportunities that present a compelling scientific rationale, have the ~~back of~~potential to address an unmet medical need and present a meaningful commercial opportunity. To the ~~eye. We reviewed a large number of assets and technology platforms during the first three quarters of 2017 and are actively continuing~~extent feasible, we plan to ~~review assets or technology platforms that would complement our strategic goals in addition to other compelling ophthalmology opportunities.~~

~~Leerink Partners continues to assist our management and our board of directors in evaluating our strategic alternatives. We, with Leerink’s assistance, have considered multiple~~target opportunities ~~over the last several months, including in-licensing, obtaining rights to products, product candidates~~where we believe third-party funding for specific programs or technologies ~~acquisitions, mergers and reverse mergers. We are committed to being opportunistic and will reconsider new compelling opportunities if and as they emerge.~~

~~Other updates~~

~~Fovista~~

In December 2016, we announced initial, top-line data from two pivotal clinical trials, OPH1002 and OPH1003, which evaluated the safety and efficacy of 1.5mg of Fovista administered in combination with monthly 0.5mg Lucentis® (ranibizumab) anti-VEGF therapy compared to monthly 0.5mg Lucentis monotherapy for the treatment of wet AMD. In August 2017, we announced initial, top-line data from the third pivotal Fovista Phase 3 trial, OPH1004, which evaluated the safety and efficacy of 1.5 mg of Fovista administered in combination with 2.0mg Eylea® (aflibercept) or 1.25mg Avastin® (bevacizumab) anti-VEGF therapy compared to 2.0mg Eylea or 1.25mg Avastin monotherapy for the treatment of wet AMD. The pre-specified primary endpoint of mean change in visual acuity at 12 months was not achieved in any of the OPH1002, OPH1003 or OPH1004 trials. Following the December 2016 data announcement, we subsequently stopped treating patients in, and terminated, both the OPH1002 and OPH1003 trials as well as our additional Phase 2 clinical trials that were evaluating the potential additional benefits of Fovista administered in combination with anti-VEGF drugs in wet AMD patients, which we have referred to collectively as the Fovista Expansion Studies. Following the August 2017 data announcement, we subsequently stopped treating patients in, and terminated, the OPH1004 trial. We are in the process of winding down the OPH1004 Fovista trial and have no future plans to develop Fovista in wet AMD.

As part of our strategic review process during 2017, we also reassessed our Fovista program and explored the scientific rationale for Fovista as a potential treatment in orphan indications. During 2016, the National Eye Institute commenced a Phase 1/2 clinical trial studying the potential role of Fovista in combination with Lucentis for the treatment of retinal capillary hemangiomas associated with the orphan disease Von-Hippel-Lindau Syndrome. This trial remains ongoing with initial data expected tomay be available during 2018. We are also planning to supply Fovista for a pre-clinical program evaluating Fovista in retinoblastoma, a rare cancer of the eye in children. Pre-clinical research has shown that the PDGFavailable.

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signaling pathway may play a role in retinoblastoma. Our commitments for these two programs primarily involve providing Fovista drug product and drug substance, which has already been manufactured, for use in these studies.

~~Novartis Agreement~~

In May 2014, we entered into a licensing and commercialization agreement with Novartis Pharma AG, or Novartis, which we refer to as the Novartis Agreement. Under the Novartis Agreement, we granted Novartis exclusive rights under specified patent rights, know-how and trademarks controlled by us to manufacture, from bulk active pharmaceutical ingredient, or API, supplied by us, standalone Fovista products and products combining Fovista with an anti-VEGF drug to which Novartis has rights in a co-formulated product, for the treatment, prevention, cure or control of any human disease, disorder or condition of the eye, and to develop and commercialize those licensed products in all countries outside of the United States, which we refer to as the Novartis Territory. We agreed to use commercially reasonable efforts to complete our pivotal Phase 3 clinical program for Fovista and Novartis agreed to use commercially reasonable efforts to develop a standalone Fovista product and a co-formulated product containing Fovista and an anti-VEGF drug to which Novartis has rights, as well as a pre-filled syringe presentation of such products and to use commercially reasonable efforts, subject to obtaining marketing approval, to commercialize licensed products in the Novartis Territory in accordance with agreed development and marketing plans. Novartis paid us a $200.0 million upfront fee upon execution of the Novartis Agreement, as well as $50.0 million upon the achievement of each of two patient enrollment-based milestones, and $30.0 million upon the achievement of a third, and final, enrollment-based milestone, for an aggregate of $330.0 million. In July 2017, we and Novartis entered into a letter agreement to streamline the process and timeline for evaluating data from the OPH1004 trial once it became available. On October 23, 2017, following the failure of the Phase 3 Fovista program and pursuant to the terms of the July 2017 letter agreement, Novartis elected to terminate the Novartis Agreement with immediate effect.

Financial Matters

~~Financial matters~~

As of ~~September 30, 2017,~~March 31, 2019, we had ~~$180.2 million in~~ cash and cash equivalents of ~~which approximately $5.0~~$116.6 million. We believe that our cash and cash equivalents will be sufficient to fund our operations and capital expenditure requirements as currently planned for at least the next 12 months. We estimate that our year end 2019 cash and cash equivalents will range between $80.0 million ~~to $7.0 million~~and $85.0 million. This estimate is ~~committed to~~based on our current business plan, including the ~~wind-down~~continued preclinical development of IC-100 and IC-200, the ~~OPH1004 trial and completing a previously announced reduction in personnel and related costs.~~

~~As a result~~continuation of our ongoing ~~reassessment~~collaborative gene therapy sponsored research programs with UMMS and Penn, the continued clinical development of Zimura, and the continued preclinical development of our ~~development programs and potential business development opportunities,~~HtrA1 inhibitor program. This estimate does not reflect any expenditures resulting from additional sponsored research agreements we may ~~modify, expand~~enter into or ~~terminate some~~the potential in-licensing or ~~all~~acquisition of ~~our development programs or clinical trials at any time. The outcome of these reassessments, as well as the progress of our plans to potentially acquire~~ additional ~~products,~~ product candidates or technologies, ~~will determine whether~~including from our ongoing collaborative gene therapy sponsored research programs, or any associated development that we may pursue following any such transaction. We have based this estimate on assumptions that may prove to be wrong, and ~~to what extent~~ we ~~will continue to incur research and development costs for each of~~could use our ~~development programs going forward.~~available capital resources sooner than we currently expect.

Our ability to become and remain profitable depends on our ability to generate revenue in excess of our expenses. We do not expect to generate significant product revenue unless, and until, we obtain marketing approval for, and commercialize, any of our product candidates, which, if we are successful, will likely take at least several years. We may be unsuccessful in our efforts to develop and commercialize these product candidates. Even if we succeed in developing and commercializing one or more of our product candidates, we may never achieve sufficient sales revenue to achieve or maintain profitability. Our capital requirements will also depend on many other factors, including whether we ~~are successful in our pursuit~~decide to acquire or in-license, and subsequently develop, additional product candidates or technologies. We ~~may need to obtain~~expect we will require substantial, additional funding in ~~connection with~~order to complete the activities necessary to develop and commercialize one or more of our ~~continuing operations.~~product candidates. If we are unable to raise capital when needed or on attractive terms, we could be forced to delay, reduce or eliminate our research and development programs or any future commercialization efforts.

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Financial Operations Overview

Revenue

~~In May 2014,~~As we ~~entered into the Novartis Agreement. We used the relative selling price method~~have no products approved for sale, we do not expect to ~~allocate arrangement consideration~~receive any revenue related to our ~~performance obligations under the Novartis Agreement. Upon entry~~product candidates until we obtain regulatory approval for and commercialize such products, or until we potentially enter into ~~the Novartis Agreement, we received an upfront payment of $200.0 million, which was not previously recorded as revenue due to our right to terminate the agreement in the event that the~~agreements with third parties ~~were prevented from materially progressing~~for the development orand commercialization of ~~Fovista products~~our product candidates. If our development efforts for ~~a specified period as a~~any of our product candidates result ~~of specified governmental actions and the associated termination fee equivalent to the entire $200.0 million upfront payment, which we would have been required to pay~~in regulatory approval or if we ~~elected to exercise this termination option. In each of September 2014 and March 2015,~~enter into agreements with third parties, we achieved a $50.0 million enrollment-based milestone, and in June 2016, we achieved a $30.0 million enrollment-based milestone, for an aggregate total of $130.0 million, under the Novartis Agreement. In July 2017, we entered into a letter agreement with Novartis, which resulted in the recognition of the remaining deferredmay generate revenue ~~under the Novartis Agreement during the~~from product sales or from such third ~~quarter of 2017, as described below under "Critical Accounting Policies and Significant Judgments and Estimates~~—~~Revenue Recognition~~—Collaboration Revenue". The recognition of this revenue during the period did not impact our cash balance. Below is a summary of the components of our collaboration revenue for the three and nine months ended September 30, 2017 and 2016:

Three months ended September 30, Nine months ended September 30,
2017 2016 2017 2016
(in thousands)
License revenue $ 152,912
$ —
$ 152,912
$ 22,937
Research and development activity revenue 52,864
1,664
56,180
8,089
API transfer revenue 754
—
754
14,545
Joint operating committee revenue 124
4
131
16
Total collaboration revenue $ 206,654
$ 1,668
$ 209,977
$ 45,587

parties.

Research and Development Expenses

~~Research~~Our research and development expenses primarily consist of costs associated with the manufacturing, development, and clinical testing ~~and manufacturing~~ of Zimura, ~~and Fovista, as well as~~ costs associated with the preclinical development of ~~other product candidates~~IC-100 and ~~formulations.~~IC-200, including related sponsored research with Penn, and costs associated with our ongoing gene therapy sponsored research programs with UMMS. Our research and development expenses consist of:

external research and development expenses incurred under arrangements with third parties, such as academic research collaborators, contract research organizations, or CROs, and CDMOs and other vendors ~~and contract manufacturing organizations, or CMOs,~~ for the production of ~~API~~drug substance and drug product; and

employee-related expenses for employees dedicated to research and development activities, including salaries, benefits and share-based compensation expense.

All research and development expenses are charged to operations as incurred in accordance with Financial Accounting Standards Board, or FASB, Accounting Standards Codification, ~~Topic,~~ or ASC, 730, Research and Development, or ASC 730. We account for non-refundable advance payments for goods and services that will be used in future research and development activities as expenses when the service has been performed or when the goods have been received, rather than when the payment is made. ~~To date, the large majority of our research and development activity has been related to Fovista and Zimura.~~ We do not currently utilize a formal time allocation system to capture expenses on a project-by-project basis because we record expenses by functional department. Accordingly, we do not allocate expenses to individual projects or product candidates, although we do allocate some portion of our research and development expenses by functional area and by ~~compound,~~product, as shown below.

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The following table summarizes our research and development expenses for the three ~~and nine~~ months ended ~~September 30, 2017~~March 31, 2019 and ~~2016:~~2018:


	Three months ended September 30,				Nine months ended September 30,				Three months ended March 31,
	2017		2016		2017		2016		2019		2018
	(in thousands)								(in thousands)
Fovista	$	4,337	$	33,160	$	21,159	$	87,696
Zimura	1,278		2,096		9,554		4,410		$	3,201	$	3,975
IC-100: RHO-adRP									848		—
IC-200: Best disease and other bestrophinopathies									145		—
Other gene therapy									248		—
Prior product candidate Fovista									13		29
Personnel-related	2,761		6,612		17,061		19,829		1,615		1,881
Share-based compensation	1,840		5,664		8,887		16,732		1,170		1,440
Other	491		3,322		1,682		8,219		445		361
	$	10,707	$	50,854	$	58,343	$	136,886	$	7,685	$	7,686

We expect ~~to continue to incur~~our research and development expenses to increase as we ~~continue~~pursue the development of IC-100, IC-200, Zimura and our ~~Zimura development programs, including as we initiate new clinical trials, and as we wind down the OPH1004 trial. Due to the terminations of the Fovista Phase 3~~HtrA1 inhibitor program, and ~~the Fovista Expansion Studies,~~in connection with our ~~overall~~collaborative gene therapy sponsored research programs. Our research and development expenses have decreased significantly compared to prior years. We expect very limited research and development expenses related to Fovista in the future. However, as we continue our Zimura development programs in age-related retinal diseases and commence new Zimura clinical trials in orphan retinal indications or asmay also increase if we commence any new development efforts ~~in relation to~~for any additional product candidates or technologies that we may in-license or ~~acquire as we pursue our updated business plan, we expect that our overall research and development expenses will begin to increase from~~acquire.

Although the ~~current level of expenditure.~~

Our expenses may exceed our expectations if we experience delays in enrollment or with the availability of drug supply for our clinical trials, if we experience any unforeseen issue in our ongoing clinical trials or if we further expand the scope of our clinical trials and programs. Our costs may also exceed our expectations for other reasons, for example, if we experience issues with process development, the scale-up of manufacturing activities or activities to enable and qualify second source suppliers or if we decide to increase licensing or preclinical research and development activities.

~~The~~ future development of our product candidates is highly ~~uncertain.~~uncertain, we expect we will require substantial, additional funding in order to complete the activities necessary to develop and commercialize one or more of our product candidates. We expect the ~~clinical~~ development ~~for Zimura~~of our product candidates will continue for at least the next several years. At this time, we cannot reasonably estimate the remaining costs necessary to complete ~~clinical~~ development, to complete process development and manufacturing ~~scale‑up~~scale-up and validation activities orand to potentially seek marketing approval with respect to our product candidates.

The successful development of our product candidates is subject to numerous risks and uncertainties associated with developing drugs, including the uncertainty of:

the scope, rate of progress and ~~expense~~costs of our research and development activities, including manufacturing activities;

the potential benefits of our product candidates over other therapies;

preclinical development results and clinical trial results;

the terms and timing of regulatory approvals;

our ability to market, commercialize and achieve market acceptance for any of our product candidates; and

our ability to successfully file, prosecute, defend and enforce patent claims and other intellectual property rights, together with associated expenses.

A change in the outcome of any of these variables with respect to the development of our product candidates could mean a significant change in the costs and timing associated with the development of that product candidate.

Our costs may exceed our expectations due to unforeseen or other reasons. For example, our costs may exceed our expectations if ~~regulatory authorities were to require us to conduct~~we experience any unforeseen issue in our ongoing clinical trials, ~~beyond those that~~such as issues with the retention of enrolled patients or with the availability of drug supply, or in our preclinical development programs, such as if we ~~currently anticipate will be required for the completion of clinical development of a product candidate~~experience issues with manufacturing or inability to develop formulations, or if we ~~experience significant delays in enrollment in any~~further expand the scope of our clinical trials, preclinical development programs or collaborative gene therapy sponsored research programs. Our costs may also exceed our expectations for other reasons, for example, if we ~~could be~~are required by the FDA, the European Medicines Agency, or EMA, or regulatory authorities in other jurisdictions to ~~expend significant~~perform clinical or nonclinical trials or other studies in addition to those we currently expect to conduct, if we experience issues with process development, establishing or scaling-up of manufacturing activities or activities to enable and qualify second source suppliers, or if we decide to increase preclinical and clinical research and development activities or build internal research capabilities or pursue internal research efforts. As a result, we may need or may seek to obtain additional ~~financial resources and time on the completion of clinical development.~~funding for our continuing operations sooner or in greater amounts than expected.

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See the “Liquidity and Capital Resources” section on page 3628 of this Quarterly Report on Form 10-Q for more information regarding our current and future financial resources and our expectations regarding our research and development expenses and funding requirements.

General and Administrative Expenses

General and administrative expenses consist primarily of salaries and related costs for personnel, including share-based compensation expense, in our executive, legal, finance, ~~commercial~~business development, human resources, investor relations and ~~business development~~information technology functions. Other general and administrative expenses include facility costs and professional fees for legal, ~~patent, pre-launch commercialization activities, travel~~including patent-related, services and expenses, consulting and accounting ~~services.~~

~~We anticipate that our general~~services, and administrative expenses will decrease in future periods as a result of a reduction in personnel to focus on an updated business plan involving a total expected workforce of approximately 36 employees. We substantially completed the reduction in personnel during the first and second quarters of 2017 as part of implementing our updated business plan.travel expenses.

Interest Income

~~Our~~We currently have invested our cash and cash equivalents ~~and marketable securities are invested primarily~~ in money market funds ~~U.S. Treasury securities~~ and investment-grade corporate debt securities, which generate a nominal amount of interest income.

Critical Accounting Policies and Significant Judgments and Estimates

Our management’s discussion and analysis of our financial condition and results of operations is based on our financial statements, which we have prepared in accordance with U.S. generally accepted accounting ~~principles.~~principles, or GAAP. The preparation of these financial statements requires us to make estimates and judgments that affect the reported amounts of assets, liabilities and expenses and the disclosure of contingent assets and liabilities in our financial statements. On an ongoing basis, we evaluate our estimates and judgments, including those related to accrued research and development expenses, revenue recognition, share-based compensation and income taxes described in greater detail below. We base our estimates on our limited historical experience, known trends and events and various other factors that we believe are reasonable under the circumstances, the results of which form the basis for making judgments about the carrying values of assets and liabilities that are not readily apparent from other sources. Actual results may differ from these estimates under different assumptions or conditions.

Our significant accounting policies are described in more detail in the notes to our financial statements appearing elsewhere in this Quarterly Report on Form 10-Q. Of those policies, we believe that the following accounting policies are the most critical to aid our stockholders in fully understanding and evaluating our financial condition and results of operations.

Accrued Research and Development Expenses

As part of the process of preparing our financial statements, we are required to estimate our accrued expenses. This process involves reviewing quotations and contracts, identifying services that have been performed on our behalf and estimating the level of service performed and the associated cost incurred for the service when we have not yet been invoiced or otherwise notified of the actual cost. The majority of our service providers invoice us monthly in arrears for services performed or when contractual milestones are met. We make estimates of our accrued expenses as of each balance sheet date in our financial statements based on facts and circumstances known to us at that time. We periodically confirm the accuracy of our estimates with the service providers and make adjustments if necessary. The significant estimates in our accrued research and development expenses are related to expenses incurred with respect to academic research collaborators, CROs, ~~CMOs~~CDMOs and other vendors in connection with research and development and manufacturing activities.

We base our expenses related to academic research collaborators, CROs and ~~CMOs~~CDMOs on our estimates of the services received and efforts expended pursuant to quotations and contracts with such vendors that conduct research and development and manufacturing activities on our behalf. The financial terms of these agreements are subject to negotiation, vary from contract to contract and may result in uneven payment flows. There may be instances in which payments made to our vendors will exceed the level of services provided and result in a prepayment of the applicable research and development or manufacturing expense. In accruing service fees, we estimate the time period over which services will be performed and the level of effort to be expended in each period. If the actual timing of the performance of services or the level of effort varies from our estimate, we adjust the accrual or prepaid expense accordingly. Although we do not expect our estimates to be materially different from amounts actually incurred, our understanding of the status and timing of services performed relative to the actual status and timing of services performed may

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vary and could result in us reporting amounts that are too high or too low in any particular period. There have been no material changes in estimates for the periods presented.

~~Revenue Recognition—Collaboration Revenue~~

In May 2014, we received an upfront payment of $200.0 million in connection with our entry into the Novartis Agreement, which was not recorded as revenue due to the existence of a contingency with respect to our right to terminate the agreement in certain circumstances and the associated termination fee equivalent to the entire $200.0 million upfront payment, which we would have been required to pay if we elected to exercise this termination option. In each of September 2014 and March 2015, we achieved a $50.0 million enrollment-based milestone, and in June 2016, we achieved a $30.0 million enrollment-based milestone, for an aggregate total of $130.0 million in milestones, under the Novartis Agreement. We used the relative selling price method to allocate these payments to contract deliverables based on our performance obligations under the Novartis Agreement.

The July 2017 letter agreement with Novartis resolved the contingency with respect to our termination right, allowing us to immediately recognize as revenue the portion of the upfront payment allocated using the relative selling price method to deliverables completed during prior periods. During the third quarter of 2017, we completed the remaining deliverables under the Novartis Agreement and the July 2017 letter agreement and recognized as revenue the balance of all of the payments previously received from Novartis related to licensing, research and development, manufacturing and joint operating committee activities that had been previously deferred using the relative selling price method. In total, during the third quarter of 2017, we recognized $206.7 million in previously deferred collaboration revenue in connection with the Novartis Agreement. The recognition of this revenue during the period did not impact our cash balance. On October 23, 2017, following the failure of the Fovista Phase 3 program and pursuant to the terms of the July 2017 letter agreement, Novartis elected to terminate the Novartis Agreement with immediate effect.

~~Below is a summary of the components of our collaboration revenue for the three and nine months ended September 30, 2017 and 2016:~~

~~Royalty Purchase Liability~~

The proceeds from the financing we received under our royalty financing agreement with Novo A/S, or the Novo Agreement, have been recorded as a liability on our Balance Sheet in accordance with ASC 730, ~~Research and Development~~. Although there is no explicit repayment obligation contained in the Novo Agreement, because there was a significant related party relationship between us and Novo A/S at the time the Novo Agreement was entered into, we are treating our obligation to make royalty payments under the Novo Agreement as an implicit obligation to repay the funds advanced by Novo A/S, and thus have recorded the proceeds as a liability on our Balance Sheet. In the event that we make royalty payments to Novo A/S, we will reduce the liability balance. At the time that such royalty payments become probable and estimable, and if such amounts exceed the liability balance, we will impute interest accordingly on a prospective basis based on such estimates, which would result in a corresponding increase in the liability balance.

Share-Based Compensation

We account for all share-based compensation payments issued to employees, non-employee directors, and consultants by estimating the fair value of each equity award. Accordingly, share-based compensation expense is measured based on the estimated fair value of the awards on the date of grant, net of forfeitures. We recognize compensation expense for the portion of

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the award that is ultimately expected to vest over the period during which the recipient renders the required services to us on a straight-line basis. In accordance with authoritative guidance, we re-measure the fair value of consultant share-based awards as the awards vest, and recognize the resulting value, if any, as expense during the period the related services are rendered.

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We apply the fair value recognition provisions of ASC 718, Compensation—Stock Compensation. Determining the amount of share-based compensation to be recorded requires us to develop estimates of the fair value of stock options as of their grant date. We recognize share-based compensation expense ratably over the requisite service period, which in most cases is the vesting period of the award. For grants containing performance-based vesting provisions, expense is recognized over the estimated achievement ~~period.~~period only when the performance-based milestone is deemed probable of achievement. If performance-based milestones are later determined not to be probable of achievement, then all previously recorded stock-based compensation expense associated with such options will be reversed during the period in which we make this determination. Calculating the fair value of share-based awards requires ~~that we~~us to make highly subjective assumptions.

Prior to January 1, 2019, share-based compensation awarded to non-employees was subject to revaluation over its vesting terms. Subsequent to the adoption of ASU 2018-07, Improvements to Non-Employee Share-Based Payment Accounting, non-employee share-based payment awards are measured on the date of grant, similar to share-based payment awards granted to employees.

We use the Black-Scholes option pricing model to value our stock option awards and the options to purchase shares under our ~~ESPP.~~employee stock purchase plan. Use of this valuation methodology requires that we make assumptions as to the volatility of our common stock, the expected term of our stock options, and the risk-free interest rate for a period that approximates the expected term of our stock options and the expected dividend yield of our common stock. As a recent public company, we do not have sufficient history to estimate the volatility of our common stock price or the expected life of the options. We calculate expected volatility based on reported data for similar publicly traded companies for which historical information is available and will continue to do so until the historical volatility of our common stock is sufficient to measure expected volatility for future option grants.

We use the simplified method as prescribed by the Securities and Exchange Commission Staff Accounting Bulletin No. 107, Share-Based Payment, to calculate the expected term of stock option grants to employees as we do not have sufficient historical exercise data to provide a reasonable basis upon which to estimate the expected term of stock options granted to employees. The risk-free interest rate used for each grant is based on the U.S. Treasury yield curve in effect at the time of grant for instruments with a similar expected life. We utilize a dividend yield of zero based on the fact that we have never paid cash dividends and have no current intention to pay cash dividends. The weighted-average assumptions used to estimate grant date fair value of stock options using the Black-Scholes option pricing model were as follows for the three ~~and nine~~ months ended ~~September 30, 2017~~March 31, 2019 and ~~2016:~~2018:


	Three months ended September 30,		Nine months ended September 30,		Three Months Ended March 31,
	2017	2016	2017	2016	2019	2018
Expected common stock price volatility	82%	71%	81%	71%	86%	81%
Risk-free interest rate	1.95%-2.06%	1.14% -1.32%	1.82%-2.38%	1.14%-1.92%	2.50%-2.54%	2.39%-2.65%
Expected term of options (years)	6.1	6.0	6.1	6.1	6.2	5.9
Expected dividend yield	—	—	—	—	—	—

We estimate the fair value of restricted stock units, or RSUs, granted to employees using the closing market price of our common stock on the date of grant.

We ~~are~~ also ~~required to~~ estimate forfeitures at the time of grant and revise those estimates in subsequent periods if actual forfeitures differ from our estimates. We use historical data to estimate pre-vesting forfeitures and record share-based compensation expense only for those awards that are expected to vest. To the extent that actual forfeitures differ from our estimates, the difference is recorded as a cumulative adjustment in the period the estimates were revised.

Share-based compensation expense for equity grants to employees, non-employee directors and consultants was ~~$3.4~~$2.5 million and ~~$8.2~~$3.1 million for the three months ended ~~September 30, 2017~~March 31, 2019 and 2016, respectively, net of expected forfeitures. Share-based compensation expense for equity grants to employees, non-employee directors and consultants was $14.4 million and $24.9 million for the nine months ended September 30, 2017 and 2016, respectively, net of expected forfeitures.2018, respectively. As of ~~September 30, 2017,~~March 31, 2019, we had ~~$22.1~~$10.6 million of total unrecognized share-based compensation expense, which we expect to recognize over a weighted-average remaining vesting period of approximately ~~2.2~~1.8 years. We expect our share-based compensation expense for our equity awards to employees, non-employee directors and consultants to decrease in future periods as a result of a decrease in our ~~reduction in force.~~

common stock fair value.

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For the three ~~and nine~~ months ended ~~September 30, 2017~~March 31, 2019 and ~~2016,~~2018, we allocated share-based compensation as follows:


	Three months ended September 30,				Nine months ended September 30,				Three Months Ended March 31,
	2017		2016		2017		2016		2019		2018
	(in thousands)								(in thousands)
Research and development	$	1,840	$	5,664	$	8,887	$	16,732	$	1,170	$	1,440
General and administrative	1,571		2,584		5,576		8,157		1,300		1,642
Total	$	3,411	$	8,248	$	14,463	$	24,889	$	2,470	$	3,082

Income Taxes

~~In 2014,~~For the three months ended March 31, 2019, we ~~received $83.3 million from Novo A/S under the Novo Agreement, which was reported as revenue~~recorded a de minimis provision for income ~~tax purposes. Also in 2014,~~taxes. For the three months ended March 31, 2018, we ~~received $200.0 million from Novartis upon execution of the Novartis Agreement,~~recorded a ~~portion of which was reported as revenue~~provision for income ~~tax purposes. In addition, we received~~taxes of $0.2 million primarily to reflect a ~~milestone payment~~reduction in the amount of $50.0 million in 2014 from Novartis which was reported as revenue for income tax purposes. As a result of these payments, and after taking into account the utilization of our federal and state net operating loss carry-forwards and utilization of our research and development tax credits, we reported taxable income for tax purposes in 2014. We made income tax payments of $40.2 million during the year ended December 31, 2014.

~~In 2015, we incurred losses for tax purposes. As of December 31, 2015, we had recorded net~~ deferred tax assets ~~of $23.1 million. We~~expected to be realized ~~these net deferred tax assets~~ in ~~2016 due to our ability to carry back our 2015 federal tax loss to 2014. We expect to carry forward a portion of our 2015 and 2016 state tax losses due to various state restrictions on~~ the ~~use of carryback claims. We are projecting tax losses for 2017.~~ future.

The deferred tax assets associated with ~~these~~our losses incurred in 2018 and to date in ~~2017~~2019 have a full valuation allowance recorded against them ~~however,~~ due to our history of losses and the lack of other positive evidence to support ~~a likelihood of~~ future taxable income against which these losses could be applied. See Note 76 to our financial statements in Part I-Item 1 of this Quarterly Report on ~~form~~Form 10-Q for further information regarding our expectations with respect to our income tax provision.

Results of Operations

Comparison of Three Month Periods Ended ~~September 30, 2017~~March 31, 2019 and ~~2016~~2018

Three months ended September 30,
2017 2016 Increase (Decrease)
(in thousands)
Statement of Operations Data:

Collaboration revenue $ 206,654
$ 1,668
$ 204,986
Operating expenses:

Research and development 10,707
50,854
(40,147 )
General and administrative 7,059
12,024
(4,965 )
Total operating expenses 17,766
62,878
(45,112 )
Income (loss) from operations 188,888
(61,210 ) (250,098 )
Interest income 391
409
(18 )
Other loss (12 ) (20 ) (8 )
Income (loss) before income tax provision 189,267
(60,821 ) (250,088 )
Income tax provision 194
70
124
Net income (loss) $ 189,073
$ (60,891 ) $ (249,964 )

~~Collaboration Revenue~~

Collaboration revenue for the three months ended September 30, 2017 was $206.7 million, an increase of $205.0 million as compared to the three months ended September 30, 2016. Collaboration revenue for the three months ended September 30, 2017 increased as we completed all deliverables required under the Novartis Agreement during the period. The July 2017 letter agreement with Novartis resolved the contingency with respect to our right to terminate the agreement in the event that the parties were prevented from materially progressing the development or commercialization of Fovista products for

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a specified period as a result of specified governmental actions and the associated termination fee equivalent to the entire $200.0 million upfront payment, which we would have been required to pay if we elected to exercise this termination option. We had previously deferred the entire $200.0 million upfront payment based on this contingency. As a result of our entry into the July 2017 letter agreement and resolution of the contingency, we immediately recognized the revenue attributable to deliverables completed during prior periods. Further, as our remaining deliverables under the Novartis Agreement and the July 2017 letter agreement were completed during the third quarter of 2017, we recognized all of the remaining collaboration revenue previously deferred under the Novartis Agreement. Using the relative selling price method, we recognized $152.9 million related to the license we delivered to Novartis under the Novartis Agreement, $52.9 million related to the research and development activities that we performed under the Novartis Agreement, $0.8 million related to Fovista API we previously transferred to Novartis, and $0.1 million related to our joint operating committee participation obligations.

Collaboration revenue for the three months ended September 30, 2016 was $1.7 million. Using the relative selling price method, the revenue we recognized during the third quarter of 2016 primarily related to the research and development activities performed under the Novartis Agreement during the same period.



	Three months ended March 31,
	2019			2018			Increase (Decrease)
	(in thousands)
Statements of Operations Data:
Operating expenses:
Research and development	7,685			7,686			(1		)
General and administrative	5,481			5,645			(164		)
Total operating expenses	13,166			13,331			(165		)
Loss from operations	(13,166		)	(13,331		)	(165		)
Interest income	670			473			197
Other expense	—			(16		)	(16		)
Loss before income tax provision	(12,496		)	(12,874		)	(378		)
Income tax provision	5			199			(194		)
Net loss	$	(12,501	)	$	(13,073	)	$	(572	)

Research and Development Expenses

Our research and development expenses were ~~$10.7~~$7.7 million for the three months ended ~~September 30, 2017, a decrease of $40.1 million~~March 31, 2019, which is relatively unchanged compared to ~~$50.9~~$7.7 million for the three months ended ~~September 30, 2016.~~March 31, 2018. Research and development expenses for the three months ended ~~September 30, 2017 include approximately $0.9~~March 31, 2019 included a $1.2 million increase in costs ~~related to~~resulting from the initiation and expansion of our ~~previously announced reduction in personnel. The decrease in research and development expenses for the three months ended September 30, 2017~~gene therapy programs. This increase was ~~primarily due to~~offset by a ~~$28.8~~$0.8 million decrease in costs associated with our ~~Fovista program, including our Fovista Phase 3 clinical program~~Zimura programs and ~~our Fovista Expansion Studies,~~ a ~~$3.9~~$0.5 million decrease in personnel expenses, a $3.8 million decrease in share-based compensation costs, a $2.0 million decrease in professional services and consulting fees and a $0.8 million decrease associated with our Zimura program, primarily related to the timing of manufacturing activities and expenses. The decreased costs for our ~~Fovista program~~Zimura programs included lower costs related to ~~Fovista~~a decrease in Zimura manufacturing activities and lower clinical trial costs as a result of the ~~wind-down~~completion of ~~OPH1002 and OPH1003~~the OPH2007 wet AMD trial and the ~~Fovista Expansion Studies.~~

completion of patient enrollment for our OPH2003 dry AMD trial.

General and Administrative Expenses

Our general and administrative expenses were ~~$7.1~~$5.5 million for the three months ended ~~September 30, 2017,~~March 31, 2019, a decrease of ~~$5.0~~$0.2 million, compared to ~~$12.0~~$5.6 million for the three months ended ~~September 30, 2016. General~~March 31, 2018. The decrease in general and administrative expenses for the three months ended September 30, 2017 include approximately $0.5 million in costs related to our previously announced reduction in personnel and the termination of facilities leases. The decrease in general and administrative expensesMarch 31, 2019 was primarily due to a decrease in costs to support our operations and ~~infrastructure offset by the additional severance costs.~~infrastructure.

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Interest Income

Interest income for the three months ended ~~September 30, 2017~~March 31, 2019 was ~~$0.4~~$0.7 million compared to ~~$0.4~~interest income of $0.5 million for the three months ended ~~September 30, 2016.~~March 31, 2018. The increase in interest income ~~earned during the three months ended September 30, 2017~~ was the result of an increase in interest rates and a change in the mix of our investment portfolio, ~~yields~~which previously only included investments in money market funds and now includes investment in certain investment-grade corporate debt securities with original maturities of 90 days or less, partially offset by a decrease in ~~our~~ cash ~~and cash equivalent~~ balances available for investment.

Income Tax Provision

WeFor the three months ended March 31, 2019, we recorded a de minimis provision for income taxes. For the three months ended March 31, 2018, we recorded a provision for income taxes of $0.2 million, ~~and $0.1 million for the three months ended September 30, 2017 and 2016, respectively~~, which primarily related to ~~discrete income tax items in each period associated with changes~~a reduction in the fair value of our available for sale marketable securities which are reflected in other comprehensive income (loss). Although we had $189.3 million of net income before income taxes for the third quarter of 2017 as a result of the recognitionamount of deferred ~~revenue under the Novartis Agreement,~~tax assets that we ~~expect a net loss for tax purposes for 2017 with minimal taxes due. For tax purposes, we treated payments received under the Novartis Agreement as revenue at the time the payments were received.~~

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~~Comparison of Nine Month Periods Ended September 30, 2017 and 2016~~

Nine months ended September 30,
2017 2016 Increase (Decrease)
(in thousands)
Statement of Operations Data:

Collaboration revenue $ 209,977
$ 45,587
$ 164,390
Operating expenses:

Research and development 58,343
136,886
(78,543 )
General and administrative 28,770
37,209
(8,439 )
Total operating expenses 87,113
174,095
(86,982 )
Income (loss) from operations 122,864
(128,508 ) (251,372 )
Interest income 1,113
1,301
(188 )
Other loss (34 ) (88 ) (54 )
Income (loss) before income tax provision (benefit) 123,943
(127,295 ) (251,238 )
Income tax provision (benefit) 196
(158 ) (354 )
Net income (loss) $ 123,747
$ (127,137 ) $ (250,884 )

~~Collaboration Revenue~~

~~Collaboration revenue for the nine months ended September 30, 2017 was $210.0 million, an increase of $164.4 million as compared~~expected to the nine months ended September 30, 2016. Collaboration revenue for the nine months ended September 30, 2017 increased as we completed all deliverables required under the Novartis Agreement during the period. The July 2017 letter agreement with Novartis resolved the contingency with respect to our right to terminate the agreementbe realized in the event that the parties were prevented from materially progressing the development or commercialization of Fovista products for a specified period as a result of specified governmental actions and the associated termination fee equivalent to the entire $200.0 million upfront payment, which we would have been required to pay if we elected to exercise this termination option. We had previously deferred the entire $200.0 million upfront payment based on this contingency. As a result of our entry into the letter agreement and resolution of the contingency, we immediately recognized the revenue attributable to deliverables completed during prior periods. Further, as our remaining deliverables under the Novartis Agreement and the letter agreement were completed during the third quarter of 2017, we recognized all of the remaining collaboration revenue previously deferred under the Novartis Agreement. Using the relative selling price method, we recognized $152.9 million related to the license we delivered to Novartis under the Novartis Agreement, $56.2 million related to the research and development activities we performed under the Novartis Agreement, $0.8 million related to Fovista API we previously transferred to Novartis, and $0.1 million related to our joint operating committee participation obligations.

Collaboration revenue for the nine months ended September 30, 2016 was $45.6 million. Using the relative selling price method, we recognized $22.9 million related to the license we delivered to Novartis under the Novartis Agreement, $8.1 million related to research and development activities performed under the Novartis Agreement, $14.5 million related to Fovista API we transferred to Novartis, and a de minimis amount of revenue related to our joint operating committee participation obligation during the same period.

~~Research and Development Expenses~~

Our research and development expenses were $58.3 million for the nine months ended September 30, 2017, a decrease of $78.5 million compared to $136.9 million for the nine months ended September 30, 2016. Research and development expenses for the nine months ended September 30, 2017 include approximately $6.8 million in costs related to our previously announced reduction in personnel. The decrease in research and development expenses for the nine months ended September 30, 2017 was primarily due to a $66.5 million decrease in costs associated with our Fovista program, including our Fovista Phase 3 clinical program and our Fovista Expansion Studies, a $5.1 million decrease in professional services and consulting fees, and a $7.8 million decrease in share-based compensation costs. The decreased costs for our Fovista program included lower costs related to Fovista manufacturing activities and lower clinical trial costs as a result of the wind-down of OPH1002 and OPH1003 and the Fovista Expansion Studies. This overall decrease was offset by a $5.1 million increase associated with our Zimura program, primarily related to manufacturing expenses, and a $2.8 million decrease to personnel expenses associated with additional severance costs.

~~General and Administrative Expenses~~

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Our general and administrative expenses were $28.8 million for the nine months ended September 30, 2017, a decrease of $8.4 million compared to $37.2 million for the nine months ended September 30, 2016. General and administrative expenses for the nine months ended September 30, 2017 include approximately $5.1 million in costs related to our previously announced reduction in force and the termination of facilities leases. The decrease in general and administrative expenses was primarily due to a decrease in costs to support our operations and infrastructure offset by the additional severance and lease termination costs.

~~Interest Income~~

Interest income for the nine months ended September 30, 2017 was $1.1 million compared to $1.3 million for the nine months ended September 30, 2016. The interest income earned during the nine months ended September 30, 2017 was the result of an increase of our investment portfolio yields offset by a decrease in our cash and cash equivalent balances available for investment.

~~Income Tax Provision (Benefit)~~

We recorded a provision for income taxes of $0.2 million and a benefit from income taxes of $0.2 million, respectively, for the nine months ended September 30, 2017 and 2016, which primarily related to discrete income tax items in each period associated with changes in the fair value of our available for sale marketable securities which are reflected in other comprehensive income (loss). Although we had $123.9 million of net income before income taxes for the nine months ended September 30, 2017 as a result of the recognition of deferred revenue under the Novartis Agreement, we expect a net loss for tax purposes for 2017 with minimal taxes due. For tax purposes, we treated payments received under the Novartis Agreement as revenue at the time the payments were received.

future.

Liquidity and Capital Resources

Sources of Liquidity

Since inception, we have financed our operations primarily through private placements of our preferred stock, venture debt borrowings, funding we received under ~~the~~our prior Fovista royalty purchase and sale agreement with Novo ~~Agreement,~~Holdings A/S, our initial public offering of common stock, which we closed in September 2013, our follow-on public offering of common stock, which we closed in February 2014, ~~and~~ funds we received under a prior licensing and commercialization agreement with Novartis Pharma, AG for Fovista, and the ~~Novartis Agreement. In September 2013,~~approximately $6.1 million in cash that we received in connection with our acquisition of Inception 4.

We currently have an effective universal shelf registration statement on Form S-3 with the Securities and Exchange Commission, to register for sale from time to time up to $150.0 million of common stock, preferred stock, debt securities, depositary shares, warrants and/or units in one or more registered offerings, of which $50.0 million may be offered, issued and sold under an ~~aggregate of 8,740,000 shares of common stock in our initial public offering at a public offering price of $22.00 per share.~~“at-the-market” Sales Agreement, or the ATM Agreement, with Cowen and Company, LLC. We ~~received net proceeds from the initial public offering of $175.6 million. In February 2014, we~~have not yet issued and sold 1,900,000 shares of common stock and selling shareholders sold 728,571 shares of common stock in a follow-on public offering at a public offering price of $31.50 per share. We received net proceeds of $55.4 million from the follow-on offering. The Novo Agreement, which is described in more detail below, provided for financing of up to $125.0 million in the aggregate in return for the sale to Novo A/S of royalty interests in worldwide sales of Fovista. We received an aggregate of $125.0 million from this financing in separate tranches in May 2013, January 2014 and November 2014, which constitutes the full amount of funding under the Novo Agreement. In May 2013, we issued and sold an aggregate of 6,666,667any shares of our ~~series C preferred~~common stock ~~at a price per share of $2.50, for an aggregate purchase price of $16.7 million. In August 2013, we issued and sold an aggregate of 13,333,333 additional shares of our series C preferred stock to~~under the ~~same purchasers at a price per share of $2.50, for an aggregate purchase price of $33.3 million.~~

In May 2014, we received an upfront payment of $200.0 million upon execution of the Novartis Agreement in connection with the grant of a license for the rights to commercialize Fovista outside the United States. In each of November 2014 and April 2015 we received payments of $50.0 million upon the achievement of two patient enrollment-based milestones, and in August 2016, $30.0 million upon the achievement of a third, and final, enrollment-based milestone, for an aggregate total of $130.0 million. In connection with the receipt of the upfront payment from Novartis, we made a milestone payment in June 2014 of approximately $19.8 million to Nektar Therapeutics, or Nektar.

ATM Agreement.

Cash Flows

As of ~~September 30, 2017,~~March 31, 2019, we had cash and cash equivalents totaling ~~$180.2~~$116.6 million and no debt. We ~~primarily invest~~currently have invested our cash and cash equivalents ~~and marketable securities~~ in ~~U.S. Treasury securities,~~ money market funds and certain investment-grade corporate debt ~~securities.~~

~~Table~~securities with original maturities of ~~Contents~~

90 days or less.

The following table shows a summary of our cash flows for the ~~nine~~three months ended ~~September 30, 2017~~March 31, 2019 and ~~2016:~~2018:


	Nine months ended September 30,						Three months ended March 31,
	2017			2016			2019			2018
	(in thousands)						(in thousands)
Net cash (used in) provided by:
Operating Activities	$	(108,576	)	$	(75,785	)	$	(14,603	)	$	(12,088	)
Investing Activities	154,792			14,130			—			—
Financing Activities	71			5,398			41			27
Net change in cash and cash equivalents	$	46,287		$	(56,257	)	$	(14,562	)	$	(12,061	)

Cash Flows from Operating Activities

Net cash used in operating activities ~~for~~in the ~~nine~~three months ended September 30, 2017 was $108.6 million and relates primarily to net cash used for the wind-down of OPH1002 and OPH1003 and the Fovista Expansion Studies, implementation of a previously announced reduction in personnel and related costs, and cancellation fees related to manufacturing commitments, as well as continuation of our OPH1004 trial through initial, top-line data in August 2017 and general and administrative and corporate infrastructure expense.

~~Net cash used in operating activities for the nine months ended September 30, 2016 was $75.8 million and~~March 31, 2019 related primarily to net cash used to fund our ~~Fovista Phase 3 program,~~research and development activities for Zimura, IC-100 and our ~~Fovista Expansion Studies, Fovista manufacturing activities, manufacturing~~other gene therapy programs and ~~clinical trial costs for~~to support our ~~Zimura program and expenditures related to~~ general and administrative ~~expenses, as well as changes~~operations. Net cash used in operating activities in the ~~components of working capital.~~

three months ended March 31, 2018 related primarily to net cash used to fund our research and development activities for Zimura and to support our general and administrative operations.

See "—Funding Requirements" below for a description of how we expect to use our cash for operating activities in future periods.

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Cash Flows from Investing Activities

~~Net~~We had no net cash provided by investing activities for the ~~nine~~three months ended ~~September 30, 2017 was $154.8 million~~March 31, 2019 and relates primarily to proceeds from the maturities of marketable securities totaling $166.8 million offset by purchases of marketable securities totaling $12.0 million. Net cash provided by investing activities for the nine months ended September 30, 2016 was $14.1 million, which related primarily to proceeds from the maturities of marketable securities totaling $62.5 million offset by purchases of marketable securities totaling $48.1 million.

March 31, 2018.

Cash Flows from Financing Activities

Net cash provided by financing activities was ~~$0.1 million~~$41 thousand for the ~~nine~~three months ended ~~September 30, 2017~~March 31, 2019 and ~~$5.4 million~~$27 thousand for the ~~nine~~three months ended ~~September 30, 2016~~March 31, 2018 and related to ~~the proceeds from stock option plan exercises and~~ purchases made under our employee stock purchase ~~plan in each respective period.~~

plan.

Funding Requirements

~~We currently have two~~Our gene therapy product candidates IC-100 and IC-200 and our HtrA1 inhibitor program are each in preclinical development, Zimura ~~and Fovista, which are~~is in clinical ~~development. Following the failure of~~development, and we are funding sponsored research programs that are ongoing at UMMS and Penn. We expect our Phase 3 Fovista program, we currently have no future plans to develop Fovista in wet AMD and very limited development activity for Fovista outside of wet AMD. We, however, expect to continue to incur significant research and development expenses to increase as we pursue ~~the development of Zimura~~these programs as currently ~~planned and wind down the Fovista OPH1004 trial. We expect very limited research and development expenses related to Fovista in the future.~~planned. We could ~~however,~~also incur additional research and development expenses ~~if we conclude that there is a scientific rationale for potentially developing, or if we undertake the development of, Zimura or Fovista in additional indications, and~~ as we evaluate and potentially in-license or acquire, and undertake development of additional product ~~candidates.~~candidates, including any promising product candidates that emerge from our collaborative gene therapy sponsored research programs. Furthermore, if we successfully develop and obtain marketing approval for any of our product candidates, we expect to incur significant commercialization expenses related to product sales, marketing, distribution and manufacturing. We are party to agreements with UFRF and Penn with respect to IC-100 and IC-200, Archemix Corp. with respect to Zimura and the former equityholders of Inception 4 with respect to our HtrA1 inhibitor program, in each case, that impose significant milestone payment obligations on us in connection with our achievement of ~~specific~~specified clinical, regulatory and commercial milestones with respect to ~~Zimura~~these product candidates or programs, as well as certain royalties on net sales with respect to IC-100 and ~~Fovista.~~IC-200. It is likely that any future in-licensing or acquisition agreements that we enter into with respect to additional ~~products,~~ product candidates or technologies would include similar obligations.

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We expect that we will continue to incur significant expenses as we:

continue the development of IC-100 and IC-200 and pursue our collaborative gene therapy sponsored research programs;

continue the clinical development of ~~Zimura as currently planned or potentially in other indications if we believe there is a sufficient scientific rationale to pursue such development;~~Zimura;

~~in‑license~~

continue the preclinical development of our HtrA1 inhibitor program;

in-license or acquire the rights to, and pursue the development of, other ~~products,~~ product candidates or technologies;

~~wind down the OPH1004 trial;~~

~~complete our previously announced reduction in personnel;~~

maintain, expand and protect our intellectual property portfolio;

hire additional clinical, manufacturing, quality control, quality assurance and scientific personnel, ifespecially as we ~~are successful in progressing the clinical development of any of~~increase our ~~product candidates;~~internal gene therapy capabilities;

seek marketing approval for any product candidates that successfully complete clinical trials;

expand our outsourced manufacturing activities ~~expand our~~or establish commercial operations ~~and establish~~or sales, marketing and distribution capabilities, if we receive, or expect to receive, marketing approval for any of our product candidates; and

expand our general and administrative functions to support our future ~~growth of the company.~~growth.

As of ~~September 30, 2017,~~March 31, 2019, we had cash and cash equivalents of $180.2 million, of which approximately $5.0 million to $7.0 million is committed to the wind-down of the OPH1004 trial and completing a previously announced reduction in personnel and related costs. We estimate that our 2017 year-end cash balance will range between $155.0 million to $165.0 million, excluding any potential business development activities or any changes to our current or planned clinical development programs. We also had $139.1 million in total liabilities as of September 30, 2017, of which $125.0 million related to the Novo Agreement, which we are required to show as a liability on our balance sheets under generally accepted accounting principles but which do not correspond to any contractual repayment obligation.

$116.6 million. We believe that our cash and cash equivalents will be sufficient to fund our operations and capital expenditure requirements as currently planned for at least the next 12 months. We estimate that our year end 2019 cash and cash equivalents will range between $80.0 million and $85.0 million. This estimate is based on our current business plan, including the continued preclinical development of IC-100 and IC-200, the continuation of our ongoing collaborative gene therapy sponsored research programs with UMMS and Penn, the continued clinical development of Zimura, and the continued preclinical development of our HtrA1 inhibitor program. This estimate does not reflect any ~~additional~~ expenditures resulting from additional sponsored research agreements we may enter into or the potential in-licensing or acquisition of additional product candidates or technologies, including from our ongoing collaborative gene therapy sponsored research programs, or any associated development that we may pursue following any such ~~transactions.~~transaction. We have based this estimate on assumptions that may prove to be wrong, and we could use our available capital resources sooner than we currently expect. ~~Our capital requirements will depend on several factors, including~~

Although the success of our pursuit, by acquisition, in-licensing or otherwise, and subsequent development of additional product candidates or technologies, and the success of our ongoing development programs. We believe that we may need additional funding in the event that we acquire or in-license one or more additional product candidates and undertake development. In addition, our expenses may exceed our expectations if we experience delays in enrollment or with the availability of drug supply for our clinical trials, if we experience any unforeseen issues in our ongoing clinical trials or if we further expand the scope of our clinical trials and programs. Our costs may also exceed our expectations for other reasons, for example, if we experience issues with manufacturing, process development, or if we are required by the FDA, the European Medicines Agency, or EMA, or regulatory authorities in other jurisdictions to perform clinical or nonclinical trials or other studies in addition to those we currently expect to conduct. As a result, we may need or may seek to obtain additional funding in connection with our continuing operations sooner than expected.

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we cannot reasonably estimate the remaining costs necessary to complete ~~the clinical~~ development, to complete process development and manufacturing ~~scale‑up~~scale-up and validation activities orand to potentially seek marketing approval with respect to our product candidates.

Our future capital requirements ~~therefore,~~ will depend on many factors, including:

the scope, progress, costs and results of our efforts to develop IC-100 and IC-200, including activities to establish manufacturing capabilities and preclinical testing to enable us to file INDs for these product candidates;

the scope, progress, costs and results from our ongoing collaborative gene therapy sponsored research programs, including costs related to the in-license and future development of any promising product candidates and technologies that emerge from these programs;

the scope, progress, costs and results of our ongoing Zimura clinical programs, ~~including~~as well as our Phase 2b clinical trial in GA, our Phase 2a clinical trial in wet AMD, our planned Phase 2b clinical trial in STGD1, our planned Phase 2a clinical trial in ICPV, and our planned Phase 2a clinical trial in non-infectious intermediate and posterior uveitis, as well

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asability to secure external funding for any additional clinical trials we may undertake to obtain data sufficient to seek marketing approval for Zimura in any indication;

the scope, progress, costs and results of our efforts to develop our HtrA1 inhibitor program, including formulation development and other preclinical development activities;

the costs, progress and timing of process development, manufacturing scale-up and validation activities and stability studies associated with our product candidates;

the extent to which we ~~in‑license~~in-license or acquire rights to, and undertake research or development of, ~~products,~~additional product candidates or technologies;

~~the amount of any upfront, milestone payments and other financial obligations associated with the in-license or acquisition of other product candidates;~~

~~the scope, progress, results and costs of preclinical development and/or clinical trials for any other product candidates that we may develop;~~

~~the costs and timing of process development and manufacturing scale‑up and validation activities associated with Zimura or any other product candidates that we may develop;~~

our ability to establish collaborations on favorable terms, if at all;

the costs, timing and outcome of regulatory filings and reviews of our product candidates;

the costs of preparing, filing and prosecuting patent applications, maintaining and protecting our intellectual property rights and defending intellectual ~~property‑related~~property-related claims;

the timing, scope and cost of commercialization activities for any of our product candidates if we receive, or expect to receive, marketing approval for a product candidate; and

subject to receipt of marketing approval, net revenue received from commercial sales of any of our product candidates, after milestone payments and royalty payments that we would be obligated to make.

Furthermore, following our receipt and announcement of initial, top-line results from our pivotal OPH1002 and OPH1003 Fovista trials for the treatment of wet AMD in December 2016, we implemented a restructuring plan that included a reduction in personnel. This reduction in personnel involves approximately 80% of our pre-announcement workforce and includes employees from nearly every department. We expect to realize estimated annualized cost savings from the reduction in personnel in the range of $25.0 million to $30.0 million starting in the third quarter of 2017. We may not realize the planned or expected cost savings benefits from this restructuring, which could adversely affect our estimate of the period for which our cash, cash equivalents and marketable securities will be sufficient to fund our operations and capital expenditure requirements as currently planned. During the first nine months of 2017, our workforce has been reduced by 112 employees in connection with the reduction in personnel and natural attrition. We expect to complete the reduction in personnel during the fourth quarter of 2017. In connection with such reduction in personnel, we estimate that we will incur approximately $13.3 million of aggregate pre-tax charges through the end of 2017, of which approximately $12.4 million in the aggregate is expected to result in cash expenditures. These pre-tax charges relate to (a) expected severance, stock compensation and other employee costs of approximately $11.2 million and (b) lease termination costs of approximately $2.1 million. As of September 30, 2017, our cash expenditures related to such reduction in personnel totaled $8.7 million.

We do not have any committed external source of funds. Our ability to raise adequate additional financing when needed, and on terms acceptable to us, will depend on many factors. These factors include investors' perceptions of the potential success of our ongoing business, including the development of our product candidates and other programs, and the potential future growth of our business. Additionally, these factors include general market conditions that also affect other companies. These factors may make raising capital difficult, and may result in us accepting terms that are unfavorable to us, especially if we are in need of financing at the particular time. The size of our company and our status as a company listed on The Nasdaq Stock Market, or Nasdaq, may also limit our ability to raise financing. For example, our ability to raise adequate financing through a public offering may be limited by market conditions and SEC rules based on our current market capitalization. Nasdaq listing rules also generally limit the number of shares we may issue in a private placement to a number less than 20% of the number of shares of our common stock outstanding immediately prior to the transaction, unless we issue such shares at a premium, which investors may be unwilling to accept, or unless we obtain shareholder approval, which can be expensive and time-consuming and can add risk to our ability to complete the financing transaction. If we are unable to raise additional funds when needed, we may be required to delay, limit, reduce or terminate the development of our product candidates, our collaborative gene therapy sponsored research programs, or our future commercialization efforts.

In addition, we may require additional funding beyond what we currently expect due to unforeseen or other reasons. For example, our costs may exceed our expectations if we experience any unforeseen issue in our ongoing clinical trials, such as issues with the retention of enrolled patients or the availability of drug supply, or in our preclinical development programs, such as inability to develop formulations or if we experience issues with manufacturing, or if we further expand the scope of our clinical trials, preclinical development programs or collaborative gene therapy sponsored research programs. Our costs may also exceed our expectations for other reasons, for example, if we are required by the FDA, the EMA or regulatory authorities in other jurisdictions to perform clinical or nonclinical trials or other studies in addition to those we currently expect to conduct, if we experience issues with process development, establishing or scaling-up of manufacturing activities or activities to enable and qualify second source suppliers, or if we decide to increase preclinical and clinical research and development activities or

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build internal research capabilities or pursue internal research efforts. As a result, we may need or may seek to obtain additional funding for our continuing operations sooner or in greater amounts than expected.

Our need for additional financing may continue even if we are able to successfully develop one or more of our product candidates. Our future commercial revenues, if any, will be derived from sales of ~~any of our~~such product candidates, ~~that we are able to successfully develop,~~ which ~~depending on the product,~~ may not be available for at least several years following completion of successful product development, if at all. In addition, if approved, our product candidates may not achieve commercial success. ~~If that is the case, we will need to obtain substantial additional financing to achieve our business objectives.~~ Even if those products are successful and we do achieve profitability, we may not be able to sustain or increase profitability on a quarterly or annual basis. Under most, if not all, of the foregoing circumstances, we may need to obtain substantial additional financing to achieve our business objectives.

Until such time, if ever, aswhen we can generate substantial product revenues, we may need or may seek to finance our operations through a combination of equity offerings, debt financings, collaborations, strategic alliances and marketing, distribution or licensing arrangements.

Adequate additional financing may not be available to us on acceptable terms, or at all. If we are unable to raise additional funds when needed, we may be required to delay, limit, reduce or terminate our product development or future commercialization efforts.

In addition, we may seek additional capital due to favorable market conditions or strategic considerations, even if we believe that we have sufficient funds for our current or future operating plans.

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To the extent that we raise additional capital through the sale of equity or convertible debt securities, our existing stockholders' ownership interests would be diluted, and the terms of these new securities may include liquidation or other preferences that adversely affect ~~their~~our existing stockholders' rights as common stockholders. The dilutive effect of future capital raises may be substantial, depending on the price of our common stock at the time of such capital raise, with a ~~common stockholder.~~lower stock price translating to greater dilution for existing stockholders. Debt financing and preferred equity financing, if available, may involve agreements that include covenants limiting or restricting our ability to take specific actions, such as incurring additional debt, making capital expenditures or declaring dividends. ~~Our pledge of assets, including intellectual property rights,~~In addition, we may issue equity securities as ~~collateral to secure~~consideration for further business development transactions, which may also dilute our ~~obligations under the Novo Agreement may limit our ability to obtain debt financing.~~ existing stockholders' ownership interests.

If we raise additional funds through collaborations, strategic alliances or marketing, distribution or licensing arrangements with third parties, we may have to relinquish valuable rights to our technologies, future revenue streams, products or product candidates or grant licenses on terms that may not be favorable to us. If we are unable to raise additional funds through equity or debt financings when needed, we may be required to grant rights to develop and market products or product candidates that we would otherwise prefer to develop and market ourselves.

~~Licensing and Commercialization~~Recent Developments - Agreements for Bestrophinopathies

BEST1 License Agreement ~~with Novartis Pharma AG~~

~~In May 2014,~~On April 11, 2019, we entered into ~~a licensing and commercialization~~an exclusive global license agreement, ~~with Novartis Pharma AG,~~ which we refer to as the ~~Novartis Agreement.~~BEST1 License Agreement, with Penn and UFRF, which we refer to collectively as the Licensors. We entered into the BEST1 License Agreement by exercising our exclusive option rights under an option agreement, or the Best1 Option Agreement, that we previously entered into with the Licensors in October 2018. Under the ~~Novartis~~BEST1 License Agreement, wethe Licensors granted ~~Novartis~~us a worldwide, exclusive ~~rights~~license under specified patent rights and specified know-how and ~~trademarks controlled by us~~a worldwide, non-exclusive license under other specified know-how to research, develop, manufacture ~~from bulk API supplied by us, standalone Fovista~~and commercialize certain AAV gene therapy products, ~~and products combining Fovista with an anti-VEGF drug to which Novartis has rights in a co-formulated product,~~including IC-200, for the treatment ~~prevention, cure or control~~ of ~~any human~~Best disease ~~disorder or condition of~~and other bestrophinopathies.

We have agreed to use commercially reasonable efforts to pursue an agreed-upon development plan with the ~~eye, and~~intent to develop ~~and commercialize those~~a licensed ~~products in all countries outside of~~product for sale within at least the United States ~~which~~and two major European countries and, subject to obtaining marketing approval, to commercialize such product in at least the United States and two major European countries. In addition, we ~~refer~~have agreed to meet specified development and regulatory milestones with respect to a licensed product by specified dates, as the ~~Novartis Territory.~~

In July 2017, we and Novartis entered into a letter agreement to streamline the process and timeline for evaluating data from the OPH1004 trial once it became available. The letter agreement provides Novartis with a fully paid-up, royalty-free license to use data from the Lucentis monotherapy arms of our Phase 2b OPH1001 trial and Phase 3 OPH1002 and OPH1003 trials in the Novartis Territory in connection with the development, manufacturing and commercialization of Novartis-controlled anti-VEGF products. The Lucentis study data license shall continue until the fifth anniversary of the letter agreement or the date the Novartis Agreement expires or terminates, whichever is later. On October 23, 2017, following the failure of the Phase 3 Fovista program and pursuant tosame may be extended under the terms of the ~~Letter Agreement, Novartis elected to terminate the Novartis Agreement with immediate effect.~~agreement.

~~Novartis~~We may grant sublicenses of the licensed patent rights and know-how, without the consent of the Licensors, to certain affiliates and to biopharmaceutical companies that have a minimum market capitalization at the time such sublicense is granted, and may otherwise grant sublicenses to the licensed patent rights and know-how with the consent of the Licensors, not to be unreasonably withheld.

Financial Terms

In May 2019, we paid usPenn, for the benefit of the Licensors, a ~~$200.0~~$0.2 million upfront license issuance fee, ~~upon execution~~which was recorded as a research and development expense, and we paid UFRF accrued patent prosecution expenses of approximately $18 thousand, which was recorded as a general and administrative expense. We have also agreed to pay Penn, for the benefit of the ~~Novartis Agreement. Novartis also paid us $50.0 million upon~~Licensors, an annual license maintenance fee in the ~~achievement~~low double-digit thousands of ~~each of two patient enrollment-based milestones, and $30.0 million upon~~dollars, which fee will be payable on an annual basis until the ~~achievement~~first commercial sale of a ~~third, and final, enrollment-based milestone, for an aggregate of $130.0 million.~~

~~Fovista Commercial API Supply Agreement with Agilent Technologies, Inc.~~

licensed product. In ~~September 2015, we entered into a Commercial Manufacturing and Supply Agreement with Agilent, pursuant to which Agilent has agreed to manufacture and supply to us, and~~addition, we have agreed to ~~purchase from Agilent, a specified percentage of our commercial requirements in all jurisdictions of Fovista API. The commercial supply agreement has an initial term that runs~~pay Penn, for ~~seven years from~~ the ~~date of our first commercial sale of Fovista, and which is subject to one two-year automatic renewal period, absent termination by either party in accordance with the terms~~benefit of the ~~commercial supply agreement. The commercial supply agreement provides for pricing for Fovista API structured on~~Licensors, a tiered basis, with the price reduced as the volume of Fovista API ordered increases. We may cancel any purchase order under the commercial supply agreement at any time, subject to the payment of specified cancellation fees. We may terminate the commercial supply agreement with no financial penaltyone-time patent grant fee in the ~~event that we cannot commercialize Fovista due to regulatory or other medical, scientific or legal reasons. Agilent may terminate~~low triple-digit thousands of dollars, upon the ~~commercial supply agreement in the event that we do not, over a specified period, purchase and take delivery from Agilent~~issuance of a specified minimum quantity of Fovista API. Each party also has the right to terminate the commercial supply agreement for other customary reasons such as material breach and bankruptcy. The commercial supply agreement contains provisions relating to compliance by Agilent with current Good Manufacturing Practices, cooperation by Agilent in connection with marketing applications for Fovista, indemnification, confidentiality, dispute resolution and other customary matters for an agreement of this kind.

In December 2016, following receipt of initial, top-line data from our pivotal OPH1002 and OPH1003 Fovista trials for the treatment of wet AMD, we canceled all of our outstanding purchase orders with Agilent for the manufacture of Fovista API for commercial drug product. In April 2017, we agreed to pay Agilent $12.7 million to satisfy our outstanding obligations for cancellation fees with respect to such canceled purchase orders, payment of which was made in April 2017.

U.S. patent that claims

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~~Clinical~~inventions disclosed in the licensed patent rights or know-how or inventions generated under certain related sponsored research agreements with Penn or UFRF, and ~~Commercial Services Agreement with Ajinomoto Althea, Inc.~~

~~In October 2016,~~that is exclusively licensed to us. Furthermore, we have agreed to reimburse Penn and ~~Ajinomoto Althea, Inc., or Althea, entered into a Clinical~~UFRF for the costs and ~~Commercial Services Agreement, which we refer to as the Fill/Finish Services Agreement.Pursuant~~expenses of patent prosecution and maintenance related to the ~~Fill/Finish Services Agreement, Althea has~~licensed patent rights.

We have further agreed to ~~provide clinical and commercial fill/finish services~~pay Penn, for ~~Zimura and Fovista, as well as any future product candidates that we and Althea may mutually agree. The Fill/Finish Services Agreement has an initial term that will expire at~~ the ~~end of 2027, absent termination by either party in accordance with the terms~~benefit of the ~~Fill/Finish Services Agreement. The initial term~~Licensors, up to an aggregate of $15.7 million if we achieve specified clinical, marketing approval and reimbursement approval milestones with respect to one licensed product, and up to an aggregate of an additional $3.1 million if we achieve these same milestones with respect to a different licensed product. In addition, we have agreed to pay Penn, for the benefit of the ~~Fill/Finish Services Agreement~~Licensors, up to an aggregate of $48.0 million if we achieve specified commercial sales milestones with respect to one licensed product, and up to an aggregate of an additional $9.6 million if we achieve these same milestones with respect to a different licensed product.

We are also obligated to pay Penn, for the benefit of the Licensors, royalties at a low single-digit percentage of net sales of licensed products. Such royalties are subject to customary deductions, credits, and reductions for lack of patent coverage and loss of regulatory exclusivity. In addition, such royalties with respect to any licensed product in any country may be ~~extended~~offset by ~~mutual agreement~~a specified portion of ~~the parties. The amount payable~~any royalty payments actually paid by us with respect to ~~Althea~~such licensed product in such country under third-party licenses to patent rights or other intellectual property rights that are necessary to research, develop, manufacture and commercialize the licensed product in such country. Our obligation to pay royalties under the ~~Fill/Finish Services~~BEST1 License Agreement is based on the volume of finished drug product that we order, subject to periodic adjustments over the term of the Fill/Finish Services Agreement. In addition, in the event that we order a specified volume of product, Althea has agreed to supply biological or pharmaceutical drug products meeting certain parameters exclusively to us.We may cancel any purchase order under the Fill/Finish Services Agreement at any time, subject to the payment of specified cancellation fees. We may terminate the Fill/Finish Services Agreement, without cause, as of any date following the third anniversary of the effective date upon six months’ prior notice to Althea. Each party also has the right to terminate the Services Agreement for other customary reasons such as material breach and bankruptcy.The Fill/Finish Services Agreement contains provisions relating to compliance by Althea with current Good Manufacturing Practices, cooperation by Althea in connection with marketing applications for our product candidates, indemnification, confidentiality, dispute resolution and other customary matters for an agreement of this kind.

In December 2016, following receipt of initial, top-line data from our pivotal OPH1002 and OPH1003 Fovista trials for the treatment of wet AMD, we canceled all of our outstanding purchase orders with Althea for the fill and finish of Fovista commercial drug product. We incurred approximately $0.6 million in connection with such cancellations in relation to non-returnable materials procured by Althea in anticipation of fulfilling such purchase orders, payment of which was made in the second quarter of 2017.

~~Royalty Financing Agreement with Novo A/S~~

In May 2013, we entered into the Novo Agreement, pursuant to which we had the ability to obtain financing in three tranches in an amount of up to $125.0 million in return for the sale to Novo A/S of aggregate royalties of a mid-single-digit percentage on worldwide sales of Fovista, with the royalty percentage determined by the amount of funding provided by Novo A/S. The three tranches of financing, in which Novo A/S purchased three low single-digit royalty interests and paid us $125.0 million in the aggregate, closed in May 2013, January 2014 and November 2014.

~~The royalty payment period begins on the commercial launch of Fovista and ends,~~will continue on a licensed product-by-licensed product and country-by-country basis onuntil the latest ~~to occur of the twelfth anniversary of the commercial launch of Fovista,~~ of:

the expiration of ~~certain~~the last-to-expire licensed patent rights covering ~~Fovista, and~~ the sale of the applicable licensed product in the country of sale;

the expiration of regulatory exclusivity ~~for Fovista,~~covering the applicable licensed product in ~~each~~the country of sale; and

10 years from the first commercial sale of the applicable ~~country. Royalty payments~~licensed product in the country of sale.

Beginning on the earlier of the calendar year following the first commercial sale of a licensed product and calendar year 2032, we are also obligated to pay certain minimum royalties, not to exceed an amount in the mid tens of thousands of dollars on an annual basis, which minimum royalties are creditable against our royalty obligation with respect to net sales of licensed products due in the year the minimum royalty is paid.

If we or any of our affiliates sublicense any of the licensed patent rights to a third party, we will be ~~payable quarterly~~obligated to pay Penn, for the benefit of the Licensors, a high single-digit to a mid teen percentage of the consideration received in ~~arrears during~~exchange for such sublicense, with the ~~royalty period. Our obligations under~~applicable percentage based upon the ~~Novo Agreement may also apply to certain other anti-PDGF, products~~stage of development of the sublicensed product at the time we ~~may develop.~~or the applicable affiliate enters into the sublicense.

~~We used~~If we receive a ~~portion~~rare pediatric disease priority review voucher from the FDA in connection with obtaining marketing approval for a licensed product and we subsequently use such priority review voucher in connection with a different product candidate outside the scope of the ~~proceeds that~~BEST1 License Agreement, we ~~initially~~will be obligated to pay Penn, for the benefit of the Licensors, aggregate payments in the low double-digit millions of dollars based on certain approval and commercial sales milestones with respect to such other product candidate. In addition, if we sell such a priority review voucher to a third party, we will be obligated to pay Penn, for the benefit of the Licensors, a high single-digit percentage of any consideration received ~~under the Novo Agreement to repay~~from such third party in ~~full an aggregate of $14.4 million of outstanding principal, interest~~connection with such sale.

Term and ~~fees under our venture debt facility and used the remaining proceeds to support clinical development and regulatory activities for Fovista and for general corporate expenses.~~Termination

The ~~Novo~~BEST1 License Agreement, ~~requires~~unless earlier terminated by us or the ~~establishment by Novo A/S and us~~Licensors, will expire upon the expiration of our obligation to pay royalties to Penn, for the benefit of the Licensors, on net sales of licensed products. Before the effectiveness of an IND for a ~~joint oversight committee~~licensed product, we may terminate the BEST1 License Agreement with respect to such licensed product or in ~~relation~~its entirety, at any time for any reason upon prior written notice to the Licensors. Following the effectiveness of an IND for a licensed product, we may terminate the BEST1 License Agreement with respect to such licensed product by providing Penn prior written notice and a certification that we are ceasing all use, research and development and commercialization of ~~Fovista in~~such licensed product, subject to certain limited exceptions. We may also terminate the ~~event that Novo A/S~~BEST1 License Agreement if Penn or UFRF materially breaches the BEST1 License Agreement and does not ~~continue~~cure such breach within a specified cure period.

The Licensors may terminate the BEST1 License Agreement if we materially breach the BEST1 License Agreement and do not cure such breach within a specified cure period, if we experience a specified insolvency event, if we cease to ~~have a representative~~carry on ~~our board of directors. The Novo Agreement also contains customary representations and warranties, as well as certain covenants relating to~~ the ~~operation~~entirety of our business ~~including covenants requiring us~~related to ~~use commercially reasonable efforts to continue our development of Fovista, to file, prosecute and maintain certain~~the licensed patent rights, ~~and, in our reasonable judgment,~~if we cease for more than four consecutive quarters to ~~pursue claims~~make any payment of infringement of our intellectual property rights. The Novo Agreement also places certain restrictions on our business, including restrictions on our ability to grant security interests in our intellectual property to third parties, to sell, transfer or out-license intellectual property, or to grant others rights to receiveearned royalties on net sales of Fovista and certain other products. We reimbursed Novo A/S for specified legal and other expenses and are required to provide Novo A/S with certain continuing information rights. We have agreed to indemnify Novo A/S and its representatives with respect to certain matters, including with respect to any third-party infringement or product liability claims relating to our products. Our obligations underlicensed products following the ~~Novo agreement are secured by a lien on certain~~commencement of ~~our intellectual property and other rights related to Fovista and other anti-PDGF products we may develop.~~commercialization thereof,

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unless such cessation is based on safety concerns that we are actively attempting to address, or if we, any of our affiliates or any of our sublicensees challenge or assist a third party in challenging the validity, scope, patentability, and/or enforceability of the licensed patent rights. If we materially breach certain diligence obligations under the BEST1 License Agreement with respect to only one licensed product, then the Licensors may only terminate our rights and licenses under the BEST1 License Agreement for such licensed product, but not for other licensed products.

Following any termination of the BEST1 License Agreement prior to expiration of the term of the BEST1 License Agreement, all rights to the licensed patent rights and know-how that the Licensors granted to us will revert to the Licensors.

Other Provisions

The BEST1 License Agreement contains patent prosecution and maintenance, indemnification and dispute resolution provisions that are customary for agreements of this kind.

BEST1 Master Sponsored Research Agreement

In October 2018, in connection with the BEST1 Option Agreement, we entered into a master sponsored research agreement with Penn, which we refer to as the BEST1 Master SRA. Under the BEST1 Master SRA, Penn agreed to perform, on a project basis, certain sponsored research relating to the subject matter of the BEST1 Option Agreement and the BEST1 License Agreement, and to provide the results of such research to us. The scope of each project and certain associated terms, including financial terms, are specified in a statement of work for each project.

Under the BEST1 Master SRA, Penn has granted us an exclusive first option to obtain, for no additional consideration and pursuant to the terms of the BEST1 License Agreement, an exclusive license to any patents or patent applications resulting from the sponsored research that is fully funded by us. In addition, under the BEST1 Master SRA, Penn has granted us an exclusive first option to negotiate to acquire an exclusive license, on commercially reasonable terms, to any patents or patent applications resulting from the sponsored research that is not fully funded by us.

The initial term of the BEST1 Master SRA expires on October 30, 2021, provided that in the event of a termination of the BEST1 Master SRA, any statements of work in effect at the time of such termination shall continue in effect, subject to the terms of the BEST1 Master SRA, until expiration or termination of the applicable statement of work. Either party may terminate the BEST1 Master SRA or a statement of work if the other party breaches any of the terms or conditions of the BEST1 Master SRA or statement of work, as applicable, and does not cure such breach within a specified cure period. In addition, either party may terminate an applicable statement of work if the services of the applicable principal investigator are no longer available to Penn and an acceptable substitute is not appointed within an agreed-upon period.

The BEST1 Master SRA contains indemnification and dispute resolution provisions that are customary for agreements of this kind.

We and Penn have entered into a series of statements of work under the BEST1 Master SRA pursuant to which Penn is conducting additional preclinical studies of IC-200, as well as natural history studies of patients with bestrophinopathies. We expect to enter into additional statements of work under the BEST1 Master SRA for additional preclinical studies. The total amount of funding for the sponsored research covered by these statements of work that we have committed to date and expect to commit to is in the low single-digit millions of dollars.

Contractual Obligations and Commitments

The following table summarizes our contractual obligations as of ~~September 30, 2017:~~March 31, 2019:

Payments Due by Period
Total Less than 1 year 1-3 years 3-5 years More than 5 years
(in thousands)
Operating Leases (1) $ 814
$ 814
$ —
$ —
$ —
Severance and Other Employee Benefits (2) 3,679
3,679
—
—
—
Total (3) $ 4,493
$ 4,493
$ —
$ —
$ —



	Payments Due by Period
	Total		Less than 1 year		1 - 3 years		3 - 5 years		More than 5 years
	(in thousands)
Sponsored Research (1)	$	1,430	$	1,430	$	—	$	—	$	—
Operating Leases (2)	1,284		1,036		248		—		—
Total (3)	$	2,714	$	2,466	$	248	$	—	$	—

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(1)	The table above includes our contracted obligations under our sponsored research agreements.

(2)

The table above includes our continuing rent obligations through ~~February 2018. On November 1, 2017,~~June 2020. In June 2018, we and One Penn Plaza LLC entered into an amendment to the lease for office space at One Penn Plaza in New York, New York extending the term of our lease, which was scheduled to expire in ~~January~~December 2018, through the end of December 2018. The incremental rental fees over the extended term of the lease are expected to be approximately $650 thousand. This additional rent is not reflected in the table above, as this commitment was entered into following September 30, 2017.June 2020.


~~(2)~~	Severance and Other Employee Benefits represents our commitments under the Board of Directors' approved plan to implement a reduction in personnel that involves approximately 80% of our workforce based on the number of employees at the time the plan was approved.

(3)

This table does not include (a) any milestone payments which may become payable to third parties under license agreements as the timing and likelihood of such payments are not known with certainty, (b) any royalty payments to third parties as the amounts, timing and likelihood of such payments are not known, (c) anticipated expenditures under supply agreements for periods for which we are not yet bound under binding purchase orders, (d) contracts that are entered into in the ordinary course of business that are not material in the aggregate in any period presented above, (e) agreements with certain employees that require the funding of a specific level of payments, if certain events, such as a termination of employment in connection with a change in control or termination of employment by the employee for good reason or by us without cause, occur and (f) our royalty purchase liability of $125.0 million as of September 30, 2017, due to the fact that the royalty payment period, if any, is not known.include:

any milestone payments which may become payable to third parties under license or acquisition agreements as the timing and likelihood of such payments are not known with certainty;

any royalty payments to third parties as the amounts, timing and likelihood of such payments are not known;

anticipated expenditures under supply agreements for periods for which we are not yet bound under binding purchase orders; or

contracts that are entered into in the ordinary course of business that are not material in the aggregate in any period presented above.

In addition to the amounts set forth in the table above, we may be required, under ~~various~~the BEST1 License Agreement and the other agreements under which we acquired rights to ~~pay royalties and~~our product candidates, to make milestone ~~payments. In addition to the Novo Agreement, these agreements include the following:~~

~~Under a license agreement with Archemix with respect to pharmaceutical products comprised of~~ payments and/or ~~derived from anti-C5 aptamers,~~pay royalties. Payments for ~~each anti-C5 aptamer~~IC-200 and any other product ~~that we may develop~~candidates licensed under the ~~agreement, including~~BEST1 License Agreement are described above. Payments for IC-100, Zimura weand our HtrA1 program are ~~obligated to make future payments to Archemix of up to an aggregate of $57.5 million if we achieve specified development, clinical~~described in "Note 9—Commitments and regulatory milestones, and up to an aggregate of $22.5 million if we achieve specified commercial milestones. We are also obligated to pay Archemix a double-digit percentage of specified non-royalty payments we may receive from any sublicensee ofContingencies" in our ~~rights under~~unaudited consolidated financial statements appearing elsewhere in this ~~license agreement. No royalties are payable to Archemix under this license agreement.~~

Under our divestiture agreement with OSI (Eyetech), Inc., or Eyetech, which agreement is now held by OSI Pharmaceuticals, LLC, or OSI Pharmaceuticals, a subsidiary of Astellas US, LLC, for rights to particular anti-PDGF aptamers, including Fovista, we are obligated to pay to OSI Pharmaceuticals future one-time payments of $12.0 million in the aggregate upon marketing approval in the United States and the European Union of a covered anti-PDGF product. We also are obligated to pay to OSI Pharmaceuticals a royalty at a low single-digit percentage of net sales of any covered anti-PDGF product we successfully commercialize.

Under a license agreement with Archemix Corp., or Archemix, with respect to pharmaceutical products comprised of or derived from any anti-PDGF aptamer, we are obligated to make future payments to Archemix of up to an aggregate of $14.0 million if we achieve specified clinical and regulatory milestones with respect to Fovista, up to an aggregate of $3.0 million if we achieve specified commercial milestones with respect to Fovista and, for each other anti-PDGF aptamer product that we may develop under the agreement, up to an aggregate of approximately $18.8 million if we achieve specified clinical and regulatory milestones and up to an aggregate of $3.0 million if we achieve specified commercial milestones. No royalties are payable to Archemix under this license agreement.

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Under a license, manufacturing and supply agreement with Nektar Therapeutics, or Nektar, for specified pegylation reagents used to manufacture Fovista, we were obligated to make future payments to Nektar of up to an aggregate of $6.5 million if we achieved specified clinical and regulatory milestones, and an additional payment of $3.0 million if we achieved a specified commercial milestone with respect to Fovista. We were obligated to pay Nektar tiered royalties at low to mid-single-digit percentages of net sales of any licensed product we successfully commercialize, with the royalty percentage determined by our level of licensed product sales, the extent of patent coverage for the licensed product and whether we have granted a third-party commercialization rights to the licensed product. In June 2014, we paid Nektar $19.8 million in connection with our entry into the Novartis Agreement. On October 27, 2017, we agreed with Nektar to terminate the license, manufacturing and supply agreement effective immediately.

Quarterly Report.

We also have letter agreements with certain employees that require the funding of a specific level of payments if certain events, such as a termination of employment in connection with a change in control or termination of employment by the employee for good reason or by us without cause, occur. For a description of these obligations, see our definitive proxy statement on Schedule 14A for our ~~2017~~2019 annual meeting of stockholders, as filed with the SEC on April ~~24, 2017.~~

In December 2016, we announced that we had determined to implement a reduction in personnel to focus on an updated business plan. In January 2017, our Board of Directors approved a plan to implement a reduction in personnel that involves approximately 80% of our workforce based on the number of employees at the time the plan was approved. We expect to realize estimated annualized cost savings from the reduction in personnel in the range of $25.0 million to $30.0 million starting in the third quarter of 2017. During the first nine months of 2017, our workforce has been reduced by 112 employees in connection with the reduction in personnel and natural attrition. We expect to complete the reduction in personnel during the fourth quarter of 2017. In connection with such reduction in personnel, we estimate that we will make cash expenditures totaling approximately $12.4 million in the aggregate, which relate to expected severance and other employee costs. As of September 30, 2017, our cash expenditures related to such reduction in personnel totaled $8.7 million.

18, 2019.

In addition, in the course of normal business operations, we have agreements with contract service providers to assist in the performance of our research and development and manufacturing activities. Expenditures to CROs and ~~CMOs~~CDMOs represent significant costs in preclinical and clinical development. Subject to required notice periods and our obligations under binding purchase orders and any cancellation fees that we may be obligated to pay, we can elect to discontinue the work under these agreements at any time. We ~~could~~may also enter into additional collaborative research, contract research, manufacturing, and supplier agreements in the future, which may require upfront payments and even long-term commitments of cash.

Off-Balance Sheet Arrangements

We did not have during the periods presented, and we do not currently have, any off-balance sheet arrangements, as defined under Securities and Exchange Commission rules.

Item 3. Quantitative and Qualitative Disclosures About Market Risk.

We are exposed to market risk related to changes in interest rates. We had cash and cash equivalents of ~~$180.2~~$116.6 millionas of ~~September 30, 2017,~~March 31, 2019, consisting of cash and investments in money market ~~funds.~~funds and certain investment-grade corporate debt securities. Our primary exposure to market risk is interest rate sensitivity, which is affected by changes in the general level of U.S. interest rates, particularly because a significant portion of our investments are in short-term securities. Due to the low risk profile of our investments, an immediate 100 basis point change in interest rates would not have a material effect on the fair market value of our portfolio.

We contract with CROs and ~~CMOs globally.~~certain other vendors to perform services outside of the United States. We may be subject to fluctuations in foreign currency rates in connection with certain of these agreements. Transactions denominated in currencies other than the U.S. dollar are recorded based on exchange rates at the time such transactions arise. As of ~~September 30, 2017,~~March 31, 2019, substantially all of our total liabilities were denominated in the U.S. dollar.

Item 4. Controls and ~~Procedures.~~

Procedures

Evaluation of Disclosure Controls and Procedures

Our management, with the participation of our ~~Chief Executive Officer~~chief executive officer and ~~Chief Financial Officer,~~chief financial officer, evaluated the effectiveness of our disclosure controls and procedures as of ~~September 30, 2017.~~March 31, 2019. The term ~~“disclosure~~"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

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company that are

~~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 Securities and Exchange ~~Commission’s~~Commission'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~~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 the evaluation of our disclosure controls and procedures as of ~~September 30, 2017,~~March 31, 2019, our ~~Chief Executive Officer~~chief executive officer and ~~Chief Financial Officer~~chief financial officer concluded that, as of such date, our disclosure controls and procedures were effective at the reasonable assurance level.

Changes in Internal Control ~~over~~Over Financial Reporting

No changes in our internal control over financial reporting (as defined in Rules 13a-15(d) and 15d-15(d) under the Exchange Act) occurred during the quarter ended ~~September 30, 2017~~March 31, 2019 that have materially affected, or are reasonably likely to materially affect, our internal control over financial reporting.

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PART ~~II—OTHER INFORMATION~~II

Item 1. Legal ~~Proceedings.~~

Proceedings

On January 11, 2017, a putative class action lawsuit was filed against us and certain of our current and former executive officers in the United States District Court for the Southern District of New York, captioned Frank Micholle v. Ophthotech Corporation, et al., No. 1:17-cv-00210. The complaint purports to be brought on behalf of shareholders who purchased our common stock between May 11, 2015 and December 12, 2016. The complaint generally alleges that we and certain of our officers violated Sections 10(b) and/or 20(a) of the Securities Exchange Act of 1934 and Rule 10b-5 promulgated thereunder by making allegedly false and/or misleading statements concerning the prospects of our Phase 3 trials for Fovista in combination with anti-VEGF drugs for the treatment of wet AMD. The complaint seeks equitable and/or injunctive relief, unspecified damages, attorneys’ fees, and other costs.

On March 9, 2017, a ~~second~~related putative class action lawsuit was filed against us and the same group of our current and former executive officers in the United States District Court for the Southern District of New York, captioned Wasson v. Ophthotech Corporation, et al., No. 1:17-cv-01758. These cases were consolidated on March 13, 2018. On June 4, 2018, the lead plaintiff filed a consolidated amended complaint, the CAC. The ~~complaint~~CAC purports to be brought on behalf of shareholders who purchased our common stock between ~~May 11,~~March 2, 2015 and December 9,12, 2016. The ~~allegations made~~CAC generally alleges that we and certain of our officers violated Sections 10(b) and/or 20(a) of the Securities Exchange Act of 1934 and Rule 10b-5 promulgated thereunder by making allegedly false and/or misleading statements concerning the results of our Phase 2b trial and the prospects of our Phase 3 trials for Fovista in combination with anti-VEGF agents for the treatment of wet AMD. The CAC seeks unspecified damages, attorneys' fees, and other costs. We and the individual defendants filed a motion to dismiss the CAC on July 27, 2018. That motion is fully briefed.

On February 7, 2018, a shareholder derivative action was filed against the members of our board of directors in the New York Supreme Court Commercial Division, captioned Cano v. Guyer, et al., No. 650601/2018. The complaint alleges that the defendants breached their fiduciary duties to our company by adopting a compensation plan that overcompensates the non-employee members of our board relative to boards of companies of comparable market capitalization and size. The complaint also alleges that the defendants were unjustly enriched as a result of the alleged conduct. The complaint purports to seek unspecified damages on our behalf, attorneys’ fees, and other costs, as well as an order directing us to reform and improve our corporate governance and internal procedures to comply with applicable laws. We filed a motion to dismiss this case on May 14, 2018. On June 4, 2018, the plaintiff filed an amended complaint. On June 25, 2018, we filed a renewed motion to dismiss this case. On December 3, 2018, the parties filed a stipulation of settlement that contemplates that we will adopt certain compensation-related governance reforms and does not obligate the defendants or us to pay any monetary damages. The court approved the settlement at a hearing on March 12, 2019. As part of the settlement, we agreed to pay approximately $300,000 in fees and costs to plaintiff's counsel. As contemplated by the settlement, our board has adopted certain compensation-related governance reforms, including a non-employee director compensation policy, which is being proposed for approval by our stockholders at our 2019 annual meeting.

On August 31, 2018, a shareholder derivative action was filed against current and former members of our board of directors and certain of our current and former officers in the United States District Court for the Southern District of New York, captioned Luis Pacheco v. David R. Guyer,et al., Case No. 1:18-cv-07999. The complaint, which is based substantially on the facts alleged in the CAC, alleges that the defendants breached their fiduciary duties to our company and wasted our corporate assets by failing to oversee our business, and also alleges that the defendants were unjustly enriched as a result of the alleged conduct, including through receipt of bonuses, stock options and similar compensation from us, and through sales of our stock between March 2, 2015 and December 12, 2016. The complaint purports to seek unspecified damages on our behalf, attorneys’ fees, and other costs, as well as an order directing us to reform and improve our corporate governance and internal procedures to comply with applicable laws, including submitting certain proposed amendments to our corporate charter, bylaws and corporate governance policies for vote by our stockholders. On December 14, 2018, we filed a motion to dismiss the complaint. That motion is fully briefed.

On October 16, 2018, our board of directors received a shareholder demand to investigate and commence legal proceedings against certain members of our board of directors. The demand alleges facts that are substantially similar to ~~those made~~the facts alleged in the ~~Micholle complaint. Putative lead plaintiffs~~CAC and the Pacheco complaint and asserts claims that are substantially similar to the claims asserted in the ~~Micholle action have moved~~Pacheco complaint. On January 30, 2019, our board of directors received a second shareholder demand from a different shareholder to ~~consolidate~~investigate and commence legal proceedings against certain current and former members of our board of directors based on allegations that are substantially similar to the ~~Micholle and Wasson actions.~~allegations contained in the first demand letter.

We deny any and all allegations of wrongdoing and intend to vigorously defend against these lawsuits. We are unable, however, to predict the outcome of these matters at this time. Moreover, any conclusion of these matters in a manner adverse to us and for which we incur substantial costs or damages not covered by our directors’ and officers’ liability insurance would have a material adverse effect on our financial condition and business. In addition, the litigation could adversely impact our reputation and divert management’s attention and resources from other priorities, including the execution of our business ~~plans~~plan and strategies that are important to our ability to grow our business, any of which could have a material adverse effect on our business.

On May 30, 2017, a shareholder derivative action was filed against the members of our Board of Directors in the United States District Court for the Southern District of New York, captioned Etelmendorf v. Bolte, et al., No. 1:17-cv-04042. The complaint alleges that defendants breached their fiduciary duties to our company by causing or permitting the company to make allegedly false and/or misleading statements concerning the prospects of our Phase 3 trials for Fovista in combination with anti-VEGF drugs for the treatment of wet AMD, and by approving certain executive compensation. The complaint also alleges that defendants were unjustly enriched as a result of the alleged conduct. The complaint purports to seek unspecified damages on our behalf, as well as an order directing us to reform and comply with its governance obligations, attorneys’ fees, and other costs. On October 17, 2017, the plaintiff filed a notice of voluntary dismissal without prejudice for this action.

Item 1A. Risk ~~Factors.~~

Factors

The following risk factors and other information included in this Quarterly Report on Form 10-Q should be carefully considered. The risks and uncertainties described below are not the only risks and uncertainties we face. Additional risks and uncertainties not presently known to us or that we presently deem less significant may also impair our business operations. Please see page 1 of this Quarterly Report on Form 10-Q for a discussion of some of the forward-looking statements that are qualified by these risk factors. If any of the following risks occur, our business, financial condition, results of operations and future growth prospects could be materially and adversely affected.

Risks Related to Our ~~Updated~~ Business Plan, Financial Position and Need for Additional Capital

We are ina development-stage company without any commercial products. The value of our company, therefore, is highly dependent on the ~~process~~success of ~~implementing a new, updated business plan that will continue to evolve as we await relevant clinical data~~our research and ~~evaluate new opportunities.~~development efforts and the amount of our available cash. Our ~~updated business plan may lead to the initiation of one or more~~research and development programs, ~~or the execution of one or more transactions that you do not agree with or that you do not perceive as favorable to your investment.~~

~~For the last several years we invested a~~which are focused on novel therapies and technologies, carry significant ~~portion of our efforts~~scientific and financial resources in the development of Fovista, administered in combination with anti‑VEGF drugs, for the treatment of wet AMD, as well as the potential commercial launch of Fovista. In December 2016, we announced the failure of our two pivotal Phase 3 clinical trials, which we refer to as OPH1002 and OPH1003, which evaluated the safety and efficacy of 1.5mg of Fovista administered in combination with monthly 0.5mg Lucentis® (ranibizumab) anti-VEGF therapy compared to monthly 0.5mg Lucentis monotherapy for the treatment of wet AMD, to meet their pre-specified primary endpoints. In August 2017, we announced the failure of our third

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pivotal Fovista Phase 3 clinical trial, OPH1004, which evaluated the safety and efficacy of 1.5 mg of Fovista administered in combination with 2.0mg Eylea® (aflibercept) or 1.25mg Avastin® (bevacizumab) anti-VEGF therapy compared to 2.0mg Eylea or 1.25mg Avastin monotherapy for the treatment of wet AMD, to meet its pre-specified primary endpoints. As a resultother risks. If any of these ~~failures, we currently have no future plans to develop Fovista in wet AMD and very limited development activity outside~~programs are not successful, the value of ~~wet AMD.~~ your investment may decline.

We ~~announced in early 2017 that we had engaged~~are a financial advisor to assist us in reviewing our strategic alternatives, including identifying potential business development opportunities. Also beginning in early 2017, we undertook a reassessment of our development plans for Zimura and Fovista, which included an evaluation of the scientific rationale for potentially developing these product candidates in one or more other ophthalmic indications for which there is a high unmet need.

In July 2017, we announced that we are pursuing a strategy to leverage our clinical experience and retina expertise to identify and develop therapies to treat multiple ophthalmic orphan diseases for which there are limited or no treatment options available. In parallel, we are continuing our on-going programs in age-related retinal diseases. We also are continuing our business development efforts to identify and potentially obtain rights to additional products, product candidates and technologies that would complement our strategic goals as well as other compelling ophthalmology opportunities.

This updated business plan requires us to be successful in a number of challenging, uncertain and risky activities, including pursuing development of Zimura in indications for which we have no human clinical data, identifying promising new assets for development that are available for acquisition or in-license and that fit our strategic focus and, if so identified, negotiating and executing an acquisition or in-license agreement for one or more of those programs on favorable terms and designing and executing a clinical program fordevelopment-stage company without any newly acquired product candidates. We may not be successful at one or more of the activities required for us to execute this new updated business plan. We are also continuing to consider other alternatives, including the acquisition of products, product candidates or technologies or other assets outside of ophthalmology, mergers or other transactions involving our company as a whole or other collaboration transactions. We cannot be sure when or if this review process will result in any type of transaction. Even if we pursue a transaction, such transaction may not be consistent with our stockholders’ expectations or may not ultimately be favorable for our stockholders, either in the shorter or longer term.

approved products. Our growth prospects and the future value of our company are highly dependent on the progress of our ~~ongoing~~research and ~~planned clinical~~development programs, including our preclinical development programs for IC-100 and IC-200, our ongoing clinical trials for Zimura, ~~together~~our ongoing preclinical development program for our HtrA1 inhibitors, and the activities being performed under our collaborative gene therapy sponsored research programs. Drug development is a highly uncertain undertaking and carries significant scientific and other risks.

We may encounter unforeseen difficulties, complications, delays, expenses and other known and unknown factors. We may never be successful in developing or commercializing any of our product candidates or other programs. There is a high rate of failure in pharmaceutical research and development. Even if we have promising preclinical or clinical candidates, their development could fail at any time. Our failure could be due to unexpected scientific, safety or efficacy issues with our product candidates and other programs, invalid hypotheses regarding the molecular targets and mechanisms of action we choose to pursue or unexpected delays in our research and development programs resulting from applying the wrong criteria or experimental systems and procedures to our programs or lack of experience, with the ~~amount~~possible result that none of our ~~remaining available cash. The~~product candidates or other programs result in the development of ~~Zimura is highly uncertain.~~marketable products. We have ~~only very limited data from small, uncontrolled~~not yet demonstrated our ability to successfully complete the development of a pharmaceutical product, including completion of large-scale, pivotal clinical trials ~~regarding the~~with safety and efficacy data sufficient to obtain marketing approval or activities necessary to apply for and obtain marketing approval, including the qualification of a commercial manufacturer through a pre-approval inspection with regulatory authorities. If successful in developing and obtaining marketing approval of one of our product candidates, we would need to transition from a company with a product development focus to a company capable of supporting commercial activities. We may not be successful in such a transition, as our company has never conducted the sales, marketing and distribution activities necessary for successful product commercialization.

Because the value of our company is largely based on the prospects for our research and development programs and their potential to result in therapies capable of achieving marketing approval and generating future revenues, any failure, delay or setback for these programs will likely have a negative impact on the value of your investment. For example, we expect to receive initial top-line data from OPH2003, our ongoing Phase 2b clinical trial of Zimura ~~as a monotherapy~~ for the treatment of GA secondary to dry AMD, during the fourth quarter of 2019. If such data are negative or do not support further development of Zimura in GA, or if we are to cease development of Zimura in STGD1 as a result of such data or for other reasons, the value of our common stock could be negatively impacted. In addition, because a number of our product candidates are in an early, preclinical stage, even if we are successful in advancing the research and development of those product candidates, the value of our common stock may not rise in a meaningful way, which could affect our ability to raise additional finances. As we continue to invest in these research and development programs to generate data to support further development, the amount of our available cash will continue to decline until such time as we raise additional finances.

We have a history of significant operating losses. We expect to continue to incur losses until such time, if ever, that we successfully commercialize our product candidates and may never achieve or maintain profitability.

Since inception, we have experienced significant cash outflows in funding our operations. To date, we have not generated any revenues from commercial product sales and have financed our operations primarily through private placements of our preferred stock, venture debt borrowings, funds received under our prior Fovista royalty purchase and sale agreement with Novo Holdings A/S, our initial public offering, which we closed in September 2013, our follow-on public offering, which

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we closed in February 2014, funds we received under our prior Fovista licensing and commercialization agreement with Novartis Pharma, AG, and funds we received in connection with our acquisition of Inception 4 in October 2018. As of March 31, 2019, we had an accumulated deficit of $434.2 million. Our net loss was $12.5 million for the three months ended March 31, 2019 and we expect to continue to incur significant operating losses for the foreseeable future.

Our gene therapy product candidates IC-100 and IC-200 and our HtrA1 inhibitor program are each in preclinical development, Zimura is in clinical development, and we are funding sponsored research programs that are ongoing at UMMS and Penn. We expect our research and development expenses to increase as we pursue these programs as currently planned. We could also incur additional research and development expenses as we evaluate and potentially in-license or acquire, and undertake development of additional product candidates, including any promising product candidates that emerge from our collaborative gene therapy sponsored research programs. Furthermore, if we successfully develop and obtain marketing approval for any of our product candidates, we expect to incur significant commercialization expenses related to product sales, marketing, distribution and manufacturing. We are party to agreements with UFRF and Penn with respect to IC-100 and IC-200, Archemix Corp. with respect to Zimura and the former equityholders of Inception 4 with respect to our HtrA1 inhibitor program, in each case, that impose significant milestone payment obligations on us in connection with our achievement of specified clinical, regulatory and commercial milestones with respect to these product candidates or programs, as well as certain royalties on net sales with respect to IC-100 and IC-200. It is likely that any future in-licensing or acquisition agreements that we enter into with respect to additional product candidates or technologies would include similar obligations.

We expect that we will continue to incur significant expenses as we:

continue the development of IC-100 and IC-200 and pursue our collaborative gene therapy sponsored research programs;

continue the clinical development of Zimura;

continue the preclinical development of our HtrA1 inhibitor program;

in-license or acquire the rights to, and pursue the development of, other product candidates or technologies;

maintain, expand and protect our intellectual property portfolio;

hire additional clinical, manufacturing, quality control, quality assurance and scientific personnel, especially as we increase our internal gene therapy capabilities;

seek marketing approval for any product candidates that successfully complete clinical trials;

expand our outsourced manufacturing activities or establish commercial operations or sales, marketing and distribution capabilities, if we receive, or expect to receive, marketing approval for any of our product candidates; and

expand our general and administrative functions to support our future growth.

Our ability to become and remain profitable depends on our ability to generate revenue in excess of our expenses. Our ability to generate revenues from product sales is dependent on our obtaining marketing approval for and commercializing our product candidates or any product candidates we may in-license or acquire. We may be unsuccessful in our efforts to develop and commercialize product candidates or in ~~combination with anti-VEGF drugs~~our efforts to in-license or acquire additional product candidates. Even if we succeed in developing and commercializing one or more of our product candidates, we may never achieve sufficient sales revenue to achieve or maintain profitability. See “—Risks Related to Product Development and Commercialization” for ~~the treatment of wet AMD or IPCV, and we have no human clinical data regarding the safety and efficacy of Zimura as~~ a treatment for autosomal recessive Stargardt disease, referred to as STGD1, or non-infectious intermediate and posterior uveitis. Our prior Zimura trials were not powered to demonstrate the efficacy of Zimura therapy with any statistical significance. We determined the sizefurther discussion of the ~~OPH2003 trial~~risks we face in ~~GA based on~~successfully developing and commercializing our ~~best estimates~~product candidates and achieving profitability.

We expect we will require substantial, additional funding in order to complete the activities necessary to develop and commercialize one or more of ~~the size~~our product candidates. If we are unable to raise capital when needed, we could be forced to delay, reduce or eliminate our product development programs or commercialization efforts. We may require additional funding beyond what we currently expect.

As of ~~trial required~~March 31, 2019, we had cash and cash equivalents of $116.6 million. We believe that our cash and cash equivalents will be sufficient to ~~demonstrate a potential clinical benefit~~fund our operations and capital expenditure requirements as currently planned for ~~Zimura.~~at least the

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next 12 months. We estimate that our year end 2019 cash and cash equivalents will range between $80.0 million and $85.0 million. This estimate is based on our ~~assumptions regarding~~current business plan, including the continued preclinical development of IC-100 and IC-200, the continuation of our ongoing collaborative gene therapy sponsored research programs with UMMS and Penn, the continued clinical development of Zimura, and the continued preclinical development of our HtrA1 inhibitor program. This estimate does not reflect any expenditures resulting from additional sponsored research agreements we may enter into or the potential ~~performance~~in-licensing or acquisition of additional product candidates or technologies, including from our ongoing collaborative gene therapy sponsored research programs, or any associated development that we may pursue following any such transaction. We have based this estimate on assumptions that may prove to be wrong, and we could use our available capital resources sooner than we currently expect.

Although the future development of our product candidates is highly uncertain, we expect we will require substantial, additional funding in order to complete the activities necessary to develop and commercialize one or more of our product candidates. We expect the development of our product candidates will continue for at least the next several years. At this time, we cannot reasonably estimate the remaining costs necessary to complete development, to complete process development and manufacturing scale-up and validation activities and to potentially seek marketing approval with respect to our product candidates.

Our future capital requirements will depend on many factors, including:

the scope, progress, costs and results of our ongoing Zimura clinical programs, as well as our ability to secure external funding for any additional clinical trials we may undertake to obtain data sufficient to seek marketing approval for Zimura in ~~this indication~~any indication;

the scope, progress, costs and results of our efforts to develop our HtrA1 inhibitor program, including formulation development and other preclinical development activities;

the costs, progress and timing of process development, manufacturing scale-up and validation activities and stability studies associated with our product candidates;

the extent to which we in-license or acquire rights to, and undertake research or development of, additional product candidates or technologies;

our ability to establish collaborations on favorable terms, if at all;

the costs, timing and outcome of regulatory filings and reviews of our product candidates;

the costs of preparing, filing and prosecuting patent applications, maintaining and protecting our intellectual property rights and defending intellectual property-related claims;

the timing, scope and cost of commercialization activities for any of our product candidates if we receive, or expect to receive, marketing approval for a product candidate; and

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financing through a public offering may be limited by market conditions and SEC rules based on our current market capitalization. Nasdaq listing rules also generally limit the number of shares we may issue in ~~part on~~a private placement to a number less than 20% of the number of shares of our common stock outstanding immediately prior to the transaction, unless we issue such shares at a premium, which investors may be unwilling to accept, or unless we obtain shareholder approval, which can be expensive and time-consuming and can add risk to our ability to complete the financing transaction. If we are unable to raise additional funds when needed, we may be required to delay, limit, reduce or terminate the development of our product candidates, our collaborative gene therapy sponsored research programs, or our future commercialization efforts.

Our need for additional financing may continue even if we are able to successfully develop one or more of our product candidates. Our future commercial revenues, if any, will be derived from sales of such product candidates, which may not be available ~~third-party clinical data.~~for at least several years following completion of successful product development, if at all. In addition, w~~e determined the size~~if approved, our product candidates may not achieve commercial success. Even if those products are successful and we do achieve profitability, we may not be able to sustain or increase profitability on a quarterly or annual basis. Under most, if not all, of the ~~OPH2005 trial~~foregoing circumstances, we may need to obtain substantial additional financing to achieve our business objectives.

In addition, we may require additional funding beyond what we currently expect due to unforeseen or other reasons. For example, our costs may exceed our expectations if we experience any unforeseen issue in ~~STDG1~~our ongoing clinical trials, such as issues with the retention of enrolled patients or the availability of drug supply, or in our preclinical development programs, such as inability to develop formulations or if we experience issues with manufacturing, or if we further expand the scope of our clinical trials, preclinical development programs or collaborative gene therapy sponsored research programs. Our costs may also exceed our expectations for other reasons, for example, if we are required by the FDA, the EMA or regulatory authorities in other jurisdictions to perform clinical or nonclinical trials or other studies in addition to those we currently expect to conduct, if we experience issues with process development, establishing or scaling-up of manufacturing activities or activities to enable and qualify second source suppliers, or if we decide to increase preclinical and clinical research and development activities or build internal research capabilities or pursue internal research efforts. As a result, we may need or may seek to obtain additional funding for our continuing operations sooner or in greater amounts than expected.

Raising additional capital may cause dilution to our stockholders, restrict our operations or require us to relinquish rights to our technologies or product candidates.

Until such time, if ever, when we can generate substantial product revenues, we may need or may seek to finance our operations through a combination of equity offerings, debt financings, collaborations, strategic alliances and marketing, distribution or licensing arrangements. In addition, we may seek additional capital due to favorable market conditions or strategic considerations, even if we believe that we have sufficient funds for our current or future operating plans. To the extent that we raise additional capital through the sale of equity or convertible debt securities, our existing stockholders' ownership interests would be diluted, and the terms of these new securities may include liquidation or other preferences that adversely affect our existing stockholders' rights as common stockholders. The dilutive effect of future capital raises may be substantial, depending on the price of our common stock at the time of such capital raise, with a lower stock price translating to greater dilution for existing stockholders. Debt financing and preferred equity financing, if available, may involve agreements that include covenants limiting or restricting our ability to take specific actions, such as incurring additional debt, making capital expenditures or declaring dividends. In addition, we may issue equity securities as consideration for further business development transactions, which may also dilute our existing stockholders' ownership interests.

For example, under the Inception 4 Merger Agreement pursuant to which we acquired Inception 4 and our HtrA1 inhibitor program, we issued an aggregate of 5,174,727 shares of our common stock as up-front consideration to the former equityholders of Inception 4. The Inception 4 Merger Agreement also requires us to make payments to the former equityholders of Inception 4 upon the achievement of certain clinical and regulatory milestones, subject to the terms and conditions set forth in the Inception 4 Merger Agreement. Those milestone payments will be in the form of shares of our common stock, calculated based on the price of our common stock over a five-trading day period preceding the achievement of the relevant milestone, unless and until the issuance of such shares would, together with all other shares issued under the Inception 4 Merger Agreement, exceed an overall maximum limit of approximately 7.2 million shares, which is equal to 19.9% of the number of ~~patients with STGD1 that we believe could potentially be enrolled within a reasonable period~~issued and outstanding shares of ~~time. Based~~our common stock as of the close of business on the ~~actual enrollment rate during~~business day prior to the ~~trial, this number~~closing date of our acquisition of Inception 4, and will be payable in cash thereafter. The issuance of additional shares as milestone consideration may ~~be increased or decreased. As STGD1 is an orphan indication, to~~dilute our knowledge there is no natural history data currently available regarding the variability for our planned primary efficacy endpoint in the STGD1 patient population we plan to enroll in this trial. Based on the information above, these trials could be underpowered to demonstrate a potential clinical benefit for Zimura in these indications.existing stockholders.

WeIf we raise additional funds through collaborations, strategic alliances or marketing, distribution or licensing arrangements with third parties, we may ~~continue~~have to ~~reassess and make changes~~relinquish valuable rights to our ~~existing development programs. Our~~technologies, future ~~plans for our Zimura development program~~revenue streams, products or product candidates or grant licenses on terms that may not be affected by the results of competitors’ clinical trials of complement inhibitors. We may modify, expand or terminate some or all of our development programs or clinical trials at any time as a result of new competitive information or as the result of changesfavorable to ~~our product pipeline as a result of business development activity.~~

~~We expect that our remaining cash balances will continue~~us. If we are unable to ~~decline as we pursue these development programs, pursue our updated business plan and until such time, if any, as we receive~~raise additional ~~funding, and the value of our stockholders’ investment may decline as a result.~~funds

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through equity or debt financings when needed, we may be required to grant rights to develop and market products or product candidates that we would otherwise prefer to develop and market ourselves.

In August 2018, we entered into an agreement with Cowen and Company, LLC, or Cowen, as agent, pursuant to which we may offer and sell shares of our common stock for aggregate gross sale proceeds of up to $50.0 million from time to time through Cowen under an “at-the-market” offering program, subject to the terms and conditions described in the agreement and SEC rules and regulations. We have not yet issued and sold any shares of common stock under our “at-the-market” offering program. If we make sales under our “at-the-market” offering program, the sales could dilute our stockholders, reduce the trading price of our common stock or impede our ability to raise future capital.

Our strategy of obtaining additional rights to ~~products,~~gene therapy product candidates or technologies for the treatment of ~~ophthalmic~~retinal diseases ~~through in~~‑~~licenses and acquisitions~~ may not be successful. ~~Our failure to successfully acquire or in-license and develop additional product candidates would likely impair our ability to grow.~~

An element of our strategy has been ~~and continues to be~~ to expand our ~~product~~ pipeline through potentially ~~in‑licensing~~in-licensing or acquiring the rights to products, product candidates or technologies that would complement our strategic ~~goals as well as other compelling ophthalmology opportunities.~~goals. Since early 2018, we have completed multiple acquisition, in-license, exclusive option and sponsored research arrangements. As we have transitioned our strategy to focus principally on gene therapy opportunities, we have decided to focus our business development efforts on obtaining rights to additional gene therapy product candidates and technologies, which we will continue to evaluate on a selective basis. Because we expect generally that we will not engage directly in internal early stage research and drug discovery efforts, the future growth of our business beyond our current product portfolio will depend ~~significantly~~ on our ability to ~~in‑license or acquire the~~obtain those rights to ~~approved products,~~ additional gene therapy product candidates, including any promising product candidates that may emerge from our collaborative gene therapy sponsored research programs. We may also continue to consider other alternatives, including mergers or other transactions involving our company as a whole or other collaboration transactions. Our business development efforts may fail to result in our acquiring rights to additional gene therapy product candidates or ~~technologies.~~ technologies, or may result in our consummating transactions with which you do not agree.

We may be unable ~~however,~~ to ~~in‑license~~in-license or acquire the rights to any such ~~products,~~gene therapy product candidates or technologies from third parties for several reasons. The success of this strategy depends partly upon our ability to identify, select and acquire or in-license promising product candidates and ~~technologies. We may be unable to identify suitable products,~~technologies, which is especially difficult for gene therapies. There is currently a limited number of available gene therapy product candidates or technologies ~~within our area~~for the retina and the competition for those assets is intense. Although we are planning to target opportunities where we believe third-party funding for specific programs or technologies may be available, funding may not in fact be available for any number of ~~focus.~~reasons. The process of proposing, negotiating and implementing a license or acquisition of a product candidate is lengthy and complex.

The ~~in‑licensing~~in-licensing and acquisition of pharmaceutical products, especially in gene therapy, is an area characterized by intense competition, and a number of companies (both more established and early stage biotechnology companies) are also pursuing strategies to ~~in‑license~~in-license or acquire ~~products,~~ product candidates or technologies that we may consider attractive. More established companies may have a competitive advantage over us due to their size, cash resources and greater research, preclinical or clinical development ~~and~~or commercialization capabilities, while earlier stage companies may be more aggressive or have a higher risk tolerance. In addition, companies that perceive us to be a competitor may be unwilling to assign or license rights to us. We also may be unable to ~~in‑license~~in-license or acquire the rights to the relevant ~~product,~~ product candidate or technology on terms that would allow us to make an appropriate return on our investment. Moreover, we may devote resources to potential acquisitions or in-licensing opportunities that are never completed, or we may fail to realize the anticipated benefits of such efforts or we may incorrectly judge the value ~~or worth~~ of an acquired or in-licensed product candidate or technology.

Further, any product candidate that we acquire or in-license would most likely require additional development efforts prior to commercial sale, including extensive clinical testing and approval by the FDA and applicable foreign regulatory authorities. All product candidates are prone to risks of failure typical of pharmaceutical product development, including the possibility that a product candidate would not be shown to be sufficiently safe and effective for approval by regulatory authorities.

If we are unable to successfully obtain rights to suitable ~~products,~~ product candidates or technologies, our business, financial condition and prospects for growth could suffer. In addition, acquisitions and in-licensing arrangements for product candidates and technologies are inherently risky, and ultimately, if we do not complete an announced acquisition or license transaction or integrate an acquired or licensed product candidate or technology successfully and in a timely manner, we may not realize the benefits of the acquisition or license to the extent anticipated and the perception of the effectiveness of our management team and our company may suffer in the marketplace. In addition, even if we are able to successfully identify, negotiate and execute one or more transactions to acquire or in-license new ~~products,~~ product candidates or technologies, our expenses and short-term costs may increase materially and adversely affect our liquidity.

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In addition, ~~future~~ acquisitions and in-licenses may entail numerous operational, financial and legal risks, including:

exposure to known and unknown liabilities, including possible intellectual property infringement claims, violations of laws, tax liabilities and commercial disputes;

incurrence of substantial debt, dilutive issuances of securities or depletion of cash to pay for acquisitions;

higher than expected acquisition and integration costs;

difficulty in combining the operations and personnel of any acquired businesses with our operations and personnel;

inability to maintain uniform standards, controls, procedures and policies;

restructuring charges related to eliminating redundancies or disposing of assets as part of any such combination;

large write-offs and difficulties in assessing the relative percentages of in-process research and development expense that can be immediately written off as compare to the amount that must be amortized over the appropriate life of the asset;

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increased amortization expenses or, in the event that we write-down the value of acquired assets, impairment losses;

impairment of relationships with key suppliers or customers of any acquired businesses due to changes in management and ownership;

inability to retain personnel, key customers, distributors, vendors and other business partners integral to an in-licensed or acquired product candidate or technology;

potential failure of the due diligence ~~processes~~process to identify significant problems, liabilities or other shortcomings or challenges of an acquired or licensed product candidate or technology, including, without limitation, problems, liabilities or other shortcomings or challenges with respect to intellectual property, product quality, revenue recognition or other accounting practices, partner disputes or issues and other legal and financial contingencies and known and unknown liabilities; and

entry into therapeutic modalities, indications or markets in which we have no or limited direct prior development or commercial experience and where competitors in such markets have stronger market positions.

~~If we are unable to successfully manage our acquisitions or other in-license transactions, our ability to develop new products and continue to expand and diversify our product pipeline may be limited.~~

We may not ~~use~~successfully integrate our ~~available cash and other sources of funding effectively as we pursue our updated business plan.~~HtrA1 inhibitor program.

Our ~~revised business plan may not be successful, or we may be unsuccessful~~acquisition of Inception 4 involves the integration of Inception 4's HtrA1 inhibitor program and technology with our existing operations and programs, and there are uncertainties inherent in ~~effectively executing~~such integration. We have devoted and will continue to devote significant management attention and resources to the Inception 4 integration and to the further development of our ~~revised business plan, which, in either case, could result~~HtrA1 inhibitor program. Delays, unexpected difficulties in the ~~expenditure of our available cash and~~integration process or failure to retain key consultants or other ~~sources of funding in ways that do not improve our results of operations or enhance the value of our common stock. The failure~~resources previously used by ~~our management to apply these funds effectively~~Inception 4 could ~~result in financial losses that could have a material adverse effect on our business, cause the price of our common stock to decline and delay~~adversely affect the development of our ~~product candidates. Pending their use,~~HtrA1 inhibitor program, our business and our financial condition. Even if we may invest our available cash in a manner that does not produce adequate income, if any, or that loses value. For example, as we implement our revised business plan, we could allocate our available capital resourcesare able to ~~pursue~~conduct the development or acquisition of a particular product candidate or technology that proves to be ineffective, or we could fail to allocate sufficient resources to strategic opportunities or product candidates or technologies that may be more profitable or for which there is a greater likelihood of success. If we fail to effectively allocate our available capital resources,integration successfully, we may not ~~be able to achieve our goals, and our financial condition and prospects for growth could suffer.~~

~~Our limited operating history may make it difficult for our stockholders to evaluate~~fully realize the ~~success~~benefits of ~~our business to date and to assess our future viability.~~

We were incorporated and commenced active operations in 2007. Our operations to date have been focused on organizing and staffing our company, acquiring rights to product candidates, business planning, raising capital and developing Fovista, Zimura and other product candidates. We have not yet demonstrated our ability to successfully completethe Inception 4 acquisition within a large‑scale, pivotal clinical trial with safety and efficacy data sufficient to obtain marketing approval, apply for and obtain marketing approval, qualify a commercial manufacturer through a pre-approval inspection with respect to anyreasonable period of our products, or conduct sales, marketing and distribution activities necessary for successful product commercialization. Consequently, any predictions about our future success or viability may not be as accurate as they could be if we had a longer operating history.

time. In addition, although we may encounter unforeseen expenses, difficulties, complications, delays and other known and unknown factors. The failure of our pivotal Phase 3 program for Fovista for the treatment of wet AMD has required us to reevaluate our future development plans for our product candidates, as well as our business plan more broadly, and has significantly decreased the likelihood that we will haveconducted a commercial product in the near term. We may never be successful in developing or commercializing any of our product candidates. If successful in developing and obtaining marketing approval of one of our product candidates, we would need to transition from a company with a product development focus to a company capable of supporting commercial activities. We may not be successful in such a transition.

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Since inception, we have experienced significant cash outflows in funding our operations. To date, we have not generated any revenues from product sales and have financed our operations primarily through private placements of our preferred stock, venture debt borrowings, funds received under our royalty purchase and sale agreement with Novo A/S, which we refer to as the Novo Agreement, which we entered into in May 2013, our initial public offering, which we closed in September 2013, our follow-on public offering, which we closed in February 2014, and funds we received under the Novartis Agreement, which we entered into in May 2014. As of September 30, 2017, we had an accumulated deficit of $475.2 million. Although we had net income of $123.7 million for the nine months ended September 30, 2017, all of the revenue associated with such net income was on account of the recognition during the period of revenue under the relative selling price method that related to the consideration that we had received in prior periods under the Novartis Agreement, which we had previously deferred. Although it is possible that we may have net income for the full year ending December 31, 2017 on account of the deferred revenue recognized this year exceeding our overall expenses, we expect to incur an operating loss for the fourth quarter of 2017 and to continue to incur significant operating losses for the foreseeable future.

We have devoted substantially all of our financial resources and efforts to the research and development of Fovista and Zimura and preparations for the potential commercial launch of Fovista, including manufacturing scale‑up activities. We expect to continue to incur significant expenses and operating losses over the next few years as we implement our updated business plan and continue to implement and reassess our development plans for our existing product candidates. Our net losses may fluctuate significantly from quarter to quarter and year to year.

We currently have two product candidates, Zimura and Fovista, which are in clinical development. Following the failure of our Phase 3 Fovista program, we currently have no future plans to develop Fovista in wet AMD and very limited development activity for Fovista outside of wet AMD. We, however, expect to continue to incur significant research and development expenses as we pursue the development of Zimura as currently planned and wind down the Fovista OPH1004 trial. We expect very limited research and development expenses related to Fovista in the future. We could, however, incur additional research and development expenses if we conclude that there is a scientific rationale for potentially developing, or if we undertake the development of, Zimura or Fovista in additional indications, and as we evaluate and potentially in-license or acquire, and undertake development of, additional product candidates. Furthermore, if we successfully develop and obtain marketing approval for any of our product candidates, we expect to incur significant commercialization expenses related to product sales, marketing, distribution and manufacturing. We are party to agreements that impose significant milestone payment obligations on us in connection with our achievement of specific clinical, regulatory and commercial milestones with respect to Zimura and Fovista. It is likely that any future in-licensing or acquisition agreements that we enter into with respect to additional products, product candidates or technologies would include similar obligations.

~~We expect that we will continue to incur significant expenses as we:~~

~~continue the clinical development of Zimura as currently planned or potentially in other indications if we believe there is a sufficient scientific rationale to pursue such development;~~

~~in‑license or acquire the rights to, and pursue the development of, other products, product candidates or technologies;~~

~~wind down the OPH1004 trial;~~

~~complete our previously announced reduction in personnel;~~

~~maintain, expand and protect our intellectual property portfolio;~~

~~hire additional clinical, manufacturing, quality control, quality assurance and scientific personnel if we are successful in progressing the clinical development of any of our product candidates;~~

~~seek marketing approval for any product candidates that successfully complete clinical trials;~~

expand our outsourced manufacturing activities, expand our commercial operations and establish sales, marketing and distribution capabilities, if we receive, or expect to receive, marketing approval for any of our product candidates; and

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~~expand our general and administrative functions to support future growth of the company.~~

We may require substantial, additional funding in order to complete the activities necessary to commercialize one or more of our product candidates. If we are unable to raise capital when needed, we could be forced to delay, reduce or eliminate our product development programs or commercialization efforts.

As of September 30, 2017, we had cash and cash equivalents of $180.2 million, of which approximately $5 million to $7 million is committed to the wind-down of the OPH1004 trial, completing a previously announced reduction in personnel and related costs. We estimate that our 2017 year-end cash balance will range between $155 million to $165 million, excluding any potential business development activities or any changes to our current or planned clinical development programs. We also had $139.1 million in total liabilities as of September 30, 2017, of which $125.0 million related to the Novo Agreement, which we are required to show as liabilities on our balance sheets under generally accepted accounting principles but which do not correspond to any contractual repayment obligation.

We believe that our cash and cash equivalents will be sufficient to fund our operations and capital expenditure requirements as currently planned for at least the next 12 months. This estimate does not reflect any additional expenditures resulting from the in-licensing or acquisition of additional product candidates or technologies or associated development that we may pursue following any such transactions. We have based this estimate on assumptions that may prove to be wrong, and we could use our available capital resources sooner than we currently expect. Our capital requirements will depend on several factors, including the success of our pursuit, by acquisition, in-licensing or otherwise, and subsequent development of additional product candidates or technologies, and the success of our ongoing development programs. We believe that we may need additional funding in the event that we acquire or in-license one or more additional product candidates and undertake development. In addition, our expenses may exceed our expectations if we experience delays in enrollment or with the availability of drug supply for our clinical trials, if we experience any unforeseen issues in our ongoing clinical trials or if we further expand the scope of our clinical trials and programs. Our costs may also exceed our expectations for other reasons, for example, if we experience issues with manufacturing,diligence process development, or if we are required by the FDA, the EMA, or regulatory authorities in other jurisdictions to perform clinical or nonclinical trials or other studies in addition to those we currently expect to conduct. As a result, we may need or may seek to obtain additional funding in connection with our continuing operations sooner than expected.

The future development of our product candidates is highly uncertain. We expect the clinical development for Zimura will continue for at least the next several years. At this time, we cannot reasonably estimate the remaining costs necessary to complete clinical development, to complete process development and manufacturing scale‑up and validation activities or to potentially seek marketing approval with respect to our product candidates.

~~Our future capital requirements, therefore, will depend on many factors, including:~~

the scope, costs and results of our Zimura clinical programs, including our Phase 2b clinical trial in GA, our Phase 2a clinical trial in wet AMD, our planned Phase 2b clinical trial in STGD1, our planned Phase 2a clinical trial in ICPV and our planned Phase 2a clinical trial in non-infectious intermediate and posterior uveitis, as well as any additional clinical trials we undertake to obtain data sufficient to seek marketing approval for Zimura in any indication;

~~the extent to which we in‑license or acquire rights to, and undertake development of products, product candidates or technologies;~~

~~the amount of any upfront, milestone payments and other financial obligations associated with the in-license or acquisition of other product candidates;~~

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~~the scope, progress, results and costs of preclinical development and/or clinical trials for any other product candidates that we may develop;~~

~~the costs and timing of process development and manufacturing scale‑up and validation activities associated with Zimura or any other product candidates that we may develop;~~

~~our ability to establish collaborations on favorable terms, if at all;~~

~~the costs, timing and outcome of regulatory reviews of our product candidates;~~

~~the costs of preparing, filing and prosecuting patent applications, maintaining and protecting our intellectual property rights and defending intellectual property‑related claims;~~

~~the timing, scope and cost of commercialization activities for any of our product candidates if we receive, or expect to receive, marketing approval for a product candidate; and~~

~~subject to receipt of marketing approval, net revenue received from commercial sales of any of our product candidates, after milestone payments and royalty payments that we would be obligated to make.~~

Furthermore, following our receipt and announcement of initial, top-line results from our pivotal OPH1002 and OPH1003 Fovista trials for the treatment of wet AMD in December 2016, we implemented a restructuring plan that included a reduction in personnel. This reduction in personnel involves approximately 80% of our pre-announcement workforce and includes employees from nearly every department. We expect to realize estimated annualized cost savings from the reduction in personnel in the range of $25 million to $30 million starting in the third quarter of 2017. During the first nine months of 2017, our workforce has been reduced by 112 employees in connection with the ~~reduction in personnel and natural attrition. We expect to complete the reduction in personnel during the fourth quarter~~acquisition of 2017. In connection with such reduction in personnel, we estimate that we will incur approximately $13.3 million of aggregate pre-tax charges through the third quarter of 2017, of which approximately $12.4 million in the aggregate is expected to result in cash expenditures. As of September 30, 2017, our cash expenditures related to such reduction in personnel totaled $8.7 million. We may not realize the planned or expected cost savings benefits from this restructuring, which could adversely affect our estimate of the period for which our cash, cash equivalents and marketable securities will be sufficient to fund our operations and capital expenditure requirements as currently planned.

We do not have any committed external source of funds. Our future commercial revenues, if any, will be derived from sales of any of our product candidates that we are able to successfully develop, which, depending on the product, may not be available for at least several years, if at all. In addition, if approved, our product candidates may not achieve commercial success. If that is the case, we will need to obtain substantial additional financing to achieve our business objectives. Even if we do achieve profitability,Inception 4, we may not yet be ~~able to sustain or increase profitability on a quarterly or annual basis.~~

~~Raising additional capital may~~aware of all factors regarding Inception 4 that could produce unintended and unexpected consequences for us. These factors could cause ~~dilution to our stockholders, restrict our operations or require~~ us to ~~relinquish rights to our technologies or product candidates.~~

Until such time, if ever, as we can generate substantial product revenues, we may need or may seek to finance our operations through a combination of equity offerings, debt financings, collaborations, strategic alliances and marketing, distribution or licensing arrangements. In addition, we may seek additional capital due to favorable market conditions or strategic considerations, even if we believe that we have sufficient funds for our current or future operating plans. To the extent that we raise additional capital through the sale of equity or convertible debt securities, our existing stockholders’ ownership interests would be diluted, and the terms of these securities may include liquidation or other preferences that adversely affect our existing stockholders’ rights as holders of our common stock. Debt financing and preferred equity financing, if available, may involve agreements that include covenants limiting or restricting our ability to take specific actions, such as incurring additional debt, making capital expenditures or declaring dividends.

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or product candidates or grant licenses on terms that may not be favorable to us. If we are unable to raise additional funds through equity or debt financings when needed, we may be required to grant rights to develop and market products or product candidates that we would otherwise prefer to develop and market ourselves.incur potentially material liabilities.

We and certain of our current and former board members and executive officers have been named as defendants in lawsuits that could result in substantial costs and divert management’s attention.

We and certain of our current and former executive officers have been named as defendants in ~~two~~a purported consolidated putative class action ~~lawsuits~~lawsuit initiated ~~earlier this year~~in 2017 that generally ~~allege~~alleges that we and certain of our officers violated Sections 10(b) and/or 20(a) of the ~~Securities~~ Exchange Act ~~of 1934~~ and Rule 10b-5 promulgated thereunder by making allegedly false and/or misleading statements concerning the results of our Phase 2b trial and the prospects of our Phase 3 trials for Fovista in combination with anti-VEGF ~~drugs~~agents for the treatment of wet AMD. Certain current and former members of our board of directors and current and former officers have also been named as defendants in a shareholder derivative action initiated in

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August 2018, which generally alleges that the defendants breached their fiduciary duties to our company by failing to oversee our business during the period of the Phase 2b and Phase 3 clinical trials of Fovista. These complaints seek equitable and/or injunctive relief, unspecified damages, attorneys’ fees, and other costs. We and the defendants deny any and all allegations of wrongdoing and intend to vigorously defend against these lawsuits. We are unable, however, to predict the outcome of these matters at this time. Moreover, any conclusion of these matters in a manner adverse to us and for which we incur substantial costs or damages not covered by our directors’ and officers’ liability insurance would have a material adverse effect on our financial condition and business. In addition, the litigation could adversely impact our reputation and divert ~~management’s~~management and our board of directors’ attention and resources from other priorities, including the execution of our business ~~plans~~plan and strategies that are important to our ability to grow our business, any of which could have a material adverse effect on our business. Additional ~~similar~~ lawsuits ~~might~~may be filed.

The comprehensive tax reform bill passed in December 2017 could adversely affect our business and financial condition.

In December 2017, United States President Donald J. Trump signed into law new legislation that significantly revised the Internal Revenue Code of 1986, as amended. The newly enacted federal income tax law, among other things, contains significant changes to corporate taxation, including reduction of the corporate tax rate from a top marginal rate of 35% to a flat rate of 21%, limitation of the tax deduction for interest expense to 30% of adjusted earnings (except for certain small businesses), limitation of the deduction for net operating losses to 80% of current year taxable income and elimination of net operating loss carrybacks, one time taxation of offshore earnings at reduced rates regardless of whether they are repatriated, elimination of U.S. tax on foreign earnings (subject to certain important exceptions), immediate deductions for certain new investments instead of deductions for depreciation expense over time, and modification or repeal of many business deductions and credits. Notwithstanding the reduction in the corporate income tax rate, the overall impact of the new federal tax law is uncertain and our business and financial condition could be adversely affected. The United States Department of Treasury and the Internal Revenue Service are continuing to issue new guidance and interpretations of various provisions of the new tax law. In addition, various states have responded in different ways to the new federal tax law. The impact of this new tax law on holders of our common stock is also uncertain and could be adverse. We urge our stockholders to consult with their legal and tax advisors with respect to this legislation and the potential tax consequences of investing in or holding our common stock.

Risks Related to Product Development and Commercialization

Companies in our industry face a wide range of challenging activities, each of which entails separate, and in many cases substantial, risk.

The long-term success of our company, and our ability to become profitable as a biopharmaceutical company, will require us to be successful in a range of challenging activities, including:

designing, conducting and successfully completing preclinical research and development activities, including preclinical efficacy and IND-enabling studies, for our product candidates or product candidates we are interested in in-licensing or acquiring, including those that we may evaluate as part of our collaborative gene therapy sponsored research programs;

making arrangements with third-party manufacturers and providers of starting materials for our product candidates, and having those manufacturers successfully develop manufacturing processes for drug substance and drug product and provide adequate amounts of drug product for preclinical and clinical activities in accordance with our expectations and regulatory requirements;

designing, conducting and completing clinical trials for our product candidates;

obtaining favorable results from required clinical trials, including for each ophthalmic product candidate, favorable results from two adequate and ~~well controlled~~well-controlled pivotal clinical trials in the relevant indication;

applying for and receiving marketing approvals from applicable regulatory authorities for the ~~use~~marketing and sale of our product candidates;

making arrangements with ~~third‑party~~third-party manufacturers for scale-up and commercial manufacturing, receiving regulatory approval of our manufacturing processes and our ~~third‑party~~third-party manufacturers’ facilities ~~from applicable regulatory authorities~~ and ensuring adequate supply of drug product and starting materials used for the manufacture of drug product;

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establishing sales, marketing and distribution capabilities, either internally or through collaborations or other arrangements, to effectively market and sell our product ~~candidates;~~candidates, if and when approved;

achieving acceptance of the product candidate, if and when approved, by patients, the medical community and ~~third‑party~~third-party payors;

if our product candidates are approved, obtaining from governmental and ~~third‑party~~third-party payors adequate coverage and reimbursement for our product candidates and, to the extent applicable, associated injection procedures conducted by treating physicians;

effectively competing with other therapies, including the existing standard of care, and other forms of drug delivery;

maintaining a continued acceptable safety profile of the product candidate during development and following approval;

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obtaining and maintaining patent and trade secret protection and regulatory exclusivity, including under the Orphan Drug Act ~~of 1983, or the Orphan Drug Act,~~ and the Hatch-Waxman Amendments to the Federal Food, Drug ~~Price Competition~~ and ~~Patent Term Restoration~~Cosmetic Act, ~~of 1984,~~ or ~~the Hatch-Waxman Act,~~FDCA, if we choose to seek such protections for any of our product candidates;

protecting and enforcing our rights in our intellectual property portfolio; and

complying with all applicable regulatory requirements, including FDA Good Laboratory Practices, or GLP, FDA Good Clinical Practices, or GCP, current Good Manufacturing Practices, or ~~GMP,~~cGMP, and standards, rules and regulations governing promotional and other marketing activities.

Each of these activities has associated risks, many of which are detailed below and throughout this “Risk Factors” section. We may never succeed in these activities and, even if we do, may never generate revenues from product sales that are significant enough to achieve commercial success and profitability. Our failure to be commercially successful and profitable would decrease the value of our company and could impair our ability to raise capital, expand our business, maintain our research and development efforts, diversify our product offerings or continue our operations. A decrease in the value of our company would also cause our stockholders to lose all or part of their investment.

Drug development is a highly uncertain undertaking. Our research and development efforts may not be successful or may be delayed for any number of reasons, in which case potential marketing approval or commercialization of our product candidates could be ~~delayed~~prevented or ~~prevented.~~delayed.

Before obtaining approval from regulatory authorities for the sale of any product candidate, we must conduct extensive clinical trials to demonstrate the safety and efficacy of our product candidates in humans. ~~Clinical~~Prior to initiating clinical trials, a sponsor must complete extensive preclinical testing of a product candidate, including, in most cases, preclinical efficacy experiments as well as IND-enabling toxicology studies. Early stage research, such as the research we are sponsoring with UMMS, may never yield a product candidate for preclinical or clinical development. Early stage research experiments and preclinical studies may fail at any point for any number of reasons, and even if completed, may be time-consuming and expensive. As a result of these risks, a potentially promising product candidate may never be tested in humans.

Once it commences, clinical testing is expensive, difficult to design and implement, can take many years to complete and is uncertain as to outcome. A failure of one or more clinical trials can occur at any stage of testing. The outcome of preclinical testing and early clinical trials may not be predictive of the success of later clinical trials, and interim results of a clinical trial do not necessarily predict final results. For example, our pivotal Phase 3 Fovista program for the treatment of wet AMD failed to produce positive safety and efficacy data that support the use of Fovista in wet AMD, despite the results from preclinical testing and earlier clinical trials of Fovista. Furthermore, our Phase 2a OPH2007 trial of Zimura in wet AMD did not replicate the results of our Phase 1/2a OPH2000 trial, following which we decided not to proceed with further development of Zimura in wet AMD. Moreover, preclinical and clinical data are often susceptible to varying interpretations and analyses, and many companies that have believed their product candidates performed satisfactorily in preclinical studies and clinical trials have nonetheless failed to obtain marketing approval of their products.

We may experience numerous unforeseen events during drug development that could delay or prevent our ability to receive marketing approval or commercialize our product candidates. ~~In particular, clinical trials of our product candidates may produce inconclusive or negative results, such as~~These risks include, but are not limited to, the results we observed in our pivotal Phase 3 Fovista program for the treatment of wet AMD. We have limited data regarding the safety, tolerability and efficacy of Zimura administered for the treatment of GA or administered in combination with anti‑VEGF drugs for the treatment of wet AMD or IPCV and no data regarding the safety, tolerability and efficacy of Zimura administered for the treatment of STGD1 or non-infectious intermediate and posterior uveitis. Given that we have limited data regarding the effect of Zimura in GA, we determined the size of the OPH2003 trial based on our best estimates of the size of trial required to demonstrate a potential clinical benefit for Zimura. This estimate is based on our assumptions regarding the potential performance of Zimura in this indication based in part on available third-party clinical data. In addition, given that we have no clinical data regarding the effect of Zimura in STGD1, we determined the size of the OPH2005 trial based on the number of patients with STGD1 that we believe could potentially be enrolled within a reasonable period of time. Based on the actual enrollment rate during the trial, this number may be increased or decreased. As STGD1 is an orphan indication, to our knowledge there is no natural history data currently available regarding the variability for our planned primary efficacy endpoint in the STGD1 patient population we plan to enroll in this trial. Based on the information above, these trials could be underpowered to demonstrate a potential clinical benefit for Zimura in these indications. In addition, some of our current and planned Zimura clinical trials, including our Phase 2b trial in GA, our Phase 2a trial in wet AMD and our planned Phase 2b trial in STGD1, are evaluating or will evaluate ~~Zimura dosing regimens that we have not studied before,~~ which may increase the risk that patients in these trials experience adverse events and/or serious adverse events (either ocular, systemic or both) that we have not observed or at rates that we have not observed in prior trials. For a further discussion of the safety risks in our trials, see the risk factor herein entitled "~~If serious adverse or unacceptable side effects are identified during the development of our product candidate, we may need to abandon or limit our development of such product candidate."~~ Moreover, the failure of prior clinical trials evaluating complement inhibition in GA, including a competitor's Phase 3 clinical trial evaluating an investigational anti-complement factor D antibody administered via intravitreal injections, a second competitor's Phase 2 clinical trial evaluating an investigational anti-C5 antibody administered via intravitreal injections and a third competitor's Phase 2 clinical trial evaluating an anti-C5 antibody administered systemically, may call into question the hypothesis underlying the use of a complement inhibitor as a method for treating GA. In addition, the anti-C5 antibody administered via intravitreal injections that was studied for the treatment of GA did not show any benefit when studied in a cohort of anti-VEGF treatment-experienced wet AMD patients. Our clinical developmentfollowing:

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~~programs may fail to produce positive safety or efficacy data that support the use of these product candidates in the indications we are pursuing.~~

~~Additional development risks include the following:~~

we may not be able to generate sufficient preclinical, toxicology, or other in vivo or in vitro data to support the initiation of clinical studies for any preclinical product candidates that we are developing or may wish to in-license or acquire;

regulators or institutional review boards may not agree with our study design, including our selection of endpoints, or may not authorize us or our investigators to commence a clinical trial or conduct a clinical trial at a prospective trial site;

we may experience delays in reaching, or fail to reach, agreement on acceptable clinical trial contracts or clinical trial protocols with prospective ~~clinical research organizations or clinical trial sites;~~

~~our~~ contract research organizations or clinical trial sites, especially in cases where we are working with contract research organizations or clinical trial sites we have not worked with previously;

our contract research organizations, clinical trial sites, contract manufacturers, providers of starting materials and packagers and analytical testing service providers may fail to comply with regulatory requirements or meet their contractual obligations to us in a timely manner, or at all;

we, through our clinical trial sites, may not be able to locate and enroll a sufficient number of eligible patients to participate in our clinical trials as required by the FDA or similar regulatory authorities outside the United States, especially in our clinical trials for orphan or other rare diseases;

we may decide, or regulators or institutional review boards may require us, to suspend or terminate clinical research for various reasons, including noncompliance with regulatory requirements, including GCPs, or a finding that the participants are being exposed to unacceptable health risks;

as there are no therapies approved for ~~either GA or~~RHO-adRP, Best disease and other bestrophinopathies, LCA10, Stargardt disease or GA in either the United States or the European Union, the regulatory pathway for product candidates in these indications, including the selection of the primary efficacy endpoint for a pivotal clinical trial, is highly uncertain;

there may be changes in regulatory requirements and guidance or we may have changes in trial design that require amending or submitting new clinical trial protocols;

there may be changes in the standard of care on which a clinical development plan was based, which may require new or additional trials;

we may decide, or regulators may require us, to conduct additional clinical trials beyond those we currently contemplate or to abandon product development programs;

the number of patients required for clinical trials of our product candidates to demonstrate statistically significant results may be larger than we anticipate, enrollment in these clinical trials may be slower than we anticipate or participants may drop out of these clinical trials at a higher rate than we anticipate. These risks may be heightened for clinical trials in orphan diseases, for which the natural history of the disease is less understood, making it more difficult to predict the drug effect required to adequately demonstrate efficacy, and because there are fewer affected ~~patients~~individuals available to participate in clinical trials;

the cost of clinical trials of our product candidates may be greater than we anticipate; ~~and~~

we or our contract manufacturers may be unable to develop a viable manufacturing process for any product candidates that we are developing;

the supply or quality of our product candidates or other materials necessary to conduct preclinical development and clinical trials of our product candidates ~~such as the anti‑VEGF drugs we need to use in combination with Zimura in our wet AMD and IPCV trials,~~ may ~~become~~be insufficient or inadequate or we may face delays in the manufacture and supply of our product candidates as a result ~~our~~of a decision to transfer manufacturing between contract manufacturers or on account of interruptions in our supply chain, including in relation to the procurement of starting materials, such as plasmids used for the manufacture of our gene therapy product candidates, and the packaging and distribution or ~~import /~~ import/export of ~~clinical materials.~~

materials and products; and

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we may face delays in the manufacture and supply of any product candidates we are investigating in our collaborative gene therapy sponsored research programs as a result of our inability to establish manufacturing capabilities or processes or to obtain necessary starting materials, such as plasmids.

If we are required to conduct additional clinical trials or other testing of our product candidates beyond those that we contemplate, if we are unable to successfully complete clinical trials or of our product candidates or other testing, if the results of these trials or tests are not positive or are only modestly positive or if there are safety concerns, we may:

be delayed in obtaining marketing approval for our product candidates;

not obtain marketing approval at all;

obtain approval for indications or patient populations that are not as broad as intended or desired;

obtain approval with labeling that includes significant use limitations, distribution restrictions or safety warnings, including boxed warnings;

be subject to additional post-marketing testing requirements; or

have the product removed from the market after obtaining marketing approval.

Despite our current development plans and ongoing efforts, we may not complete any of our ongoing or planned clinical trials ~~or other clinical trials~~ for our product candidates. ~~Moreover, the~~The timing of the completion of, and the availability of results from, clinical trials is difficult to predict. Furthermore, our development plans may change based on feedback we may receive from regulatory authorities throughout the development process. If we experience delays in testing or marketing approvals, our product development costs would increase. We do not know whether clinical trials will begin as planned, will need to be restructured or will be completed on schedule, or at all. Furthermore, our development plans may change based on feedback we may receive from regulatory authorities throughout the development process. If we experience delays in manufacturing, testing or marketing approvals, our product development costs would increase. Significant clinical trial delays also could ~~shorten~~allow our competitors to bring products to market before we do, impair our ability to successfully commercialize our product candidates, including by shortening any periods during which we may have the exclusive right to commercialize our product candidates, ~~or allow our competitors to bring products to market before we do and impair our ability to successfully commercialize our product candidates~~ and may otherwise harm our business and results of operations.

Gene therapy is an emerging field of drug development that poses many scientific and other risks. We have only limited prior experience in gene therapy research and manufacturing and no prior experience in gene therapy clinical development. Our lack of experience may limit our ability to be successful or may delay our development efforts.

Gene therapy is an emerging field of drug development with only one gene replacement therapy having received FDA approval to date. Our gene therapy research and development programs, which we decided to undertake based on a review of a limited set of preclinical data, are still at a very early stage. Even with promising preclinical data, there remains several areas of drug development risk, including translational science, manufacturing materials and processes, safety concerns, regulatory pathway and clinical trial design and execution, which pose particular uncertainty for our programs given the relatively limited development history of, and our limited prior experience with, gene therapies. For example from a translational science perspective, we decided to in-license and pursue the development of IC-200 based on results observed in an autosomal recessive canine bestrophinopathy model. A majority of humans with bestrophinopathies, however, have the autosomal dominant form of the disease, commonly referred to as Best disease, and we intend to develop IC-200 for this patient population and other patient populations with bestrophinopathies. The approach to treating human patients with the autosomal dominant form of the disease with a construct previously studied in an autosomal recessive canine disease model may ultimately prove ineffective.

We have particularly focused on adeno-associated virus, or AAV, gene therapy, as AAV vectors are relatively specific to retinal cells and their safety profile in humans is relatively well-documented as compared to other delivery vehicles and gene therapy technologies currently in development. However, AAV has a number of drawbacks, including its small packaging capacity (an AAV vector can hold only up to approximately 4,700 base pairs of DNA, whereas the genes for a number of IRDs, such as Stargardt disease, exceed that size). Although AAV is the most commonly used vector in ocular gene therapy today, it may prove to pose safety risks that we are not aware of and other vector forms, such as retroviral or lentiviral and non-viral based vectors, or gene editing approaches, may prove to be safer and more effective.

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Although we believe gene therapy is a promising area for retinal drug development, our gene therapy research and development experience is limited to only a few personnel hired to supervise our outside service providers. In pursuing this new technology, we have begun to establish our own gene therapy technical capabilities, but we will need to continue to build those capabilities by either hiring internally or seeking assistance from outside service providers. We believe that gene therapy is an area of significant investment by biotechnology and pharmaceutical companies and that there may be a scarcity of talent available to us in these areas. If we are not able to expand our gene therapy capabilities, we may not be able to develop in the way we intend or desire, IC-100, IC-200 or any promising product candidates that emerge from our collaborative gene therapy sponsored research programs, which would limit our prospects for future growth.

For a further discussion of the risks associated with the manufacturing of gene therapy products, see the risk factor herein entitled "The manufacture of gene therapy products is complex with a number of scientific and technical risks, some of which are common to the manufacture of drugs and biologics and others are unique to the manufacture of gene therapies. We have limited experience with gene therapy manufacturing and are dependent on our third-party contract manufacturers and sole source suppliers".

Our development of Zimura is based on a novel mechanism of action that is unproven and poses a number of scientific and other risks, and we may not be successful in developing Zimura in the indications we are pursuing. Our ongoing and any future clinical trials for Zimura may not provide sufficient safety and efficacy data to support future development efforts or seeking and obtaining marketing approval.

We are targeting GA, an advanced form of dry AMD, and STGD1 with Zimura. The causes of AMD are not completely understood. In addition to advanced age, there are environmental and genetic risk factors that contribute to the development of AMD including ocular pigmentation, dietary factors, a positive family history for AMD, high blood pressure and smoking. Although we believe there is a scientific rationale for pursuing the development of inhibitors for selective molecular targets, including complement C5, as potential pharmaceutical treatments for AMD, this approach may not prove successful for treating AMD in a clinically meaningful way. Similarly, although there is non-clinical scientific literature supporting the potential use of inhibitors of the complement system for the treatment of STGD1, this approach may not prove clinically successful as well.

Zimura is designed to inhibit complement C5. There are no FDA or EMA approved products that utilize C5 inhibition as a mechanism of action to treat GA or STGD1, and this mechanism of action may not prove safe and effective for these diseases. Moreover, the failure of prior clinical trials evaluating complement inhibition in GA, including a competitor's two Phase 3 clinical trials evaluating an investigational anti-complement factor D antibody administered via intravitreal injections, a second competitor's Phase 2 clinical trial evaluating an investigational anti-C5 antibody administered via intravitreal injections and a third competitor's Phase 2 clinical trial evaluating an anti-C5 antibody administered systemically, may call into question the hypothesis underlying the use of a complement inhibitor as a method for treating GA.

We have only very limited data from a small, uncontrolled clinical trial regarding the safety and efficacy of Zimura as a monotherapy for the treatment of GA, and we have no human clinical data regarding the safety and efficacy of Zimura as a treatment for STGD1. Our prior Zimura trials were not powered to demonstrate the efficacy of Zimura therapy with statistical significance. Our ongoing and any future clinical trials for Zimura that we or a potential future partner may undertake may fail to demonstrate sufficient safety or efficacy to justify further development or to ultimately seek or obtain marketing approval. Any negative results from our ongoing or any future clinical trials for Zimura, including from our OPH2003 trial for which we expect initial top-line data to be available during the fourth quarter of 2019, could adversely affect our business and the value of your investment in our company.

The statistical analysis of a clinical trial outcome is primarily determined based on three factors: variability in the measured endpoint among the patient population, the magnitude of the drug effect observed in relation to that variability and the number of patients from whom data is collected in the clinical trial. Given that we have limited data regarding the effect of Zimura in GA, we determined the size of the OPH2003 trial in GA based on our best estimates of the size of trial required to demonstrate a potential clinical benefit for Zimura. This estimate incorporates our assumptions regarding the potential performance of Zimura in this indication based in part on available third-party clinical trial data and our statistical analysis of this data, as well as our assumptions regarding the number of patients that will continue to participate in the trial and from whom we will be able to collect data through the 12-month timepoint. In addition, although we initially determined the size of the OPH2005 trial in STGD1 based on the number of patients with STGD1 that we believed could potentially be enrolled within a reasonable period of time, we decided to cease patient enrollment during the first quarter of 2019 in light of the 18-month endpoint and our goal of providing initial top-line data from this trial by the end of 2020. As STGD1 is an orphan indication, to our knowledge there is only very limited natural history data currently available regarding the variability for our planned primary efficacy endpoint in the STGD1 patient population we enrolled in this trial. Moreover, because both GA and

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Stargardt disease are degenerative diseases, and in many cases, the rate of degeneration is slow, and because we are seeking to slow the progression of degeneration with Zimura, and not necessarily to reverse prior degeneration or restore visual function, patients participating in our trials may not perceive a benefit from continuing to participate and therefore may drop out of the trial. Although we and the investigators participating in our trials and their staff take efforts to encourage continued patient participation, the drop-out rate for our Zimura trials may exceed our expectations. A higher than expected drop-out rate would reduce the number of patients from whom data is available for analyzing the primary endpoint for these trials.Given the information above, these trials could be underpowered to demonstrate a potential clinical benefit for Zimura in these indications.

Furthermore, our ongoing Zimura clinical trials are evaluating Zimura dosing levels and regimens that we have studied previously only in a small number of patients, and this approach may increase the risk that patients in our ongoing trials experience adverse events and/or serious adverse events (either ocular, systemic or both) that we have not observed or at rates that we have not observed in prior trials. Although we did not observe adverse events or serious adverse events attributable to the drug product in our recently completed OPH2007 trial, previously unobserved adverse events and/or serious adverse events may manifest in our current Zimura clinical trials. For a further discussion of the safety risks in our trials, see the risk factor herein entitled "If serious adverse or unacceptable side effects are identified during the development of our product candidates, we may need to abandon or limit our development of such product candidates."

Our development of our HtrA1 inhibitor program is also based on a novel mechanism of action that is unproven and poses a number of scientific and other risks. We may not be able to successfully formulate a product candidate from our HtrA1 inhibitors.

Our HtrA1 inhibitor program is in preclinical development. There are no FDA or EMA approved products that utilize HtrA1 inhibition as a mechanism of action for treating ophthalmic diseases, including GA and other age-related retinal diseases for which we may develop our HtrA1 inhibitor program, and this mechanism of action may not prove safe and effective for these diseases. We made the decision to acquire this program based on our interpretation of the scientific literature and rationale for this potential target that suggest an association between HtrA1 and the risk for AMD, as well as a limited set of preclinical data generated by Inception 4 prior to the acquisition. We note, however, the HtrA1 gene is in the same region of the 10q26 chromosome as the age-related maculopathy susceptibility 2, or ARMS2, gene. The ARMS2 and HtrA1 genes are linked, and variants in, or expression of, the ARMS2 gene may also be associated with the risk for AMD. The risk for AMD associated with ARMS2 may ultimately prove to be greater than the risk associated with HtrA1. In addition, even though genetic and histologic findings correlate HtrA1 with AMD, the development and progression of AMD may not be affected by HtrA1. Our assumption that targeting inhibition of HtrA1 as a method of treating AMD may be incorrect, which would likely adversely affect the value of our HtrA1 inhibitor program and its continued development.

Before we can commence IND-enabling studies for our HtrA1 inhibitor program, we need to conduct pre-formulation and formulation studies with our lead compounds in this program to determine whether we can formulate a product candidate for intravitreal administration that is safe to advance into preclinical studies and, depending on the outcome of such studies, into clinical trials. As part of this work, we need to determine which inactive formulation components should be used in the preparation of the product candidate, and derive a preparation that includes an adequate amount of drug substance with the necessary inactive ingredients to achieve the desired safety profile for intravitreal injection into the eye while providing for sufficient pharmacological activity. Formulation development is inherently uncertain, and it is possible we may not be able to formulate any of our lead compounds into a preparation that is safe to advance into preclinical studies or clinical trials in the eye or that provides sufficient pharmacological activity, which would hinder our ability to pursue development of this program. Formulation development can be time-consuming and our anticipated timelines for the development of this program may be delayed.

If serious adverse or unacceptable side effects are identified during the development of our product ~~candidate,~~candidates, we may need to abandon or limit our development of such product ~~candidate.~~candidates.

If any of our product candidates are associated with serious adverse events or undesirable side effects in preclinical studies or clinical trials or have characteristics that are unexpected, we may need to abandon their development or limit development to certain uses or subpopulations in which the undesirable side effects or other characteristics are less prevalent, less severe or more acceptable from a ~~risk‑benefit~~risk-benefit perspective. Many compounds that initially showed promise in clinical or earlier stage testing have later been found to cause side effects that prevented further development of the compound.

WeIn particular, we have limited data regarding the safety, tolerability and efficacy of Zimura administered for the treatment of GA ~~or administered in combination with anti‑VEGF drugs for the treatment of wet AMD or IPCV~~ and no data regarding the safety, tolerability and efficacy of Zimura administered for the treatment of ~~STGD1~~STGD1.

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In our completed clinical trials for Zimura, we have observed only a single adverse event, mild subcapsular cataract, from our OPH2000 trial, assessed to be drug-related by participating investigators. We have no human data regarding IC-100, IC-200 or ~~non-infectious intermediate and posterior uveitis.~~ any of our HtrA1 inhibitors.

Our clinical trials for Zimura involve dosing regimens that we have not studied ~~before,~~extensively, which may increase the risk that patients in these trials experience adverse events and/or serious adverse events (either ocular, systemic or both) that we have not observed or at rates that we have not observed in prior trials. In addition, our clinical trials for Zimura ~~will~~ involve multiple intravitreal injections over an extended period of time and, as such, may involve risks regarding multiple and chronic intravitreal injections. For these reasons, there may be, among others, an increase in the rates of intraocular infections, or endophthalmitis, intraocular pressure, glaucoma, retinal tears, cataracts, retinal detachment, intraocular inflammation, retinal and/or choroidal circulation compromise, ~~cardiovascular disease such as myocardial infarctions, stroke, blood clots or emboli,~~ or hospitalizations in patients who receive Zimura. Because we currently have only one product candidate in clinical development, it is possible that a safety issue in any of our ongoing clinical trials for Zimura ~~monotherapy~~could impact all of our then-ongoing clinical trials.

As HtrA1 inhibition is a novel treatment approach for treating ocular disease, this treatment modality may present potentially unknown safety risks when tested in clinical trials that could not have been anticipated based on preclinical toxicology studies. In addition, if we are successful in formulating an HtrA1 product candidate, we intend to administer the product candidate by intravitreal injection, which poses the same safety risks outlined above with respect to intravitreal injections of Zimura.

In addition, there are several known safety risks specific to gene therapy, including inflammation resulting from a patient's immune response to the administration of viral vectors and the potential for toxicity as a result of chronic exposure to the expressed protein. Managing a host body's immune response to introduced viral vectors has been and remains a challenge for gene therapies. For AAV gene therapy, "vector shedding," or ~~Zimura~~the dispersal of AAV vectors away from the target tissue to other parts of the body, which can trigger a more serious and extensive immune response, is a known safety issue. Although subretinal injection, which is the method often used to administer ocular gene therapies, helps to control vector shedding beyond the eye, subretinal injection is a surgical procedure that requires significant skill and training for the administering surgeon and involves its own risks separate from the gene therapy vectors, including the risk of retinal detachment. In order to avoid accelerating damage to a subject's retina, subretinal injection for RHO-adRP patients in ~~combination~~particular must be conducted under extremely low light levels using infrared technology, further complicating the surgical procedure. The margin for error with ~~anti-VEGF therapy.~~subretinal injections is extremely low and there are a limited number of retinal surgeons with experience in performing subretinal injections in the eye. In the event that we progress into clinical development with IC-100, IC-200 or any other gene therapy product candidate we may in-license or acquire, we may experience delays or other challenges for our gene therapy development programs as a result of safety issues. For example, in order to generate useful clinical data for any of those gene therapy clinical trials, a retinal surgeon must repeat the same subretinal injection process multiple times and with consistency.

~~Our experience~~In addition to the currently known safety risks, there may be unknown risks to human health from gene therapies. Because gene therapy involves the introduction of concentrated quantities of AAV, as well as the introduction of persistent foreign genetic material into the human body, any safety risks may not manifest until much later, if at all. Gene therapies have only recently been used in the treatment of human diseases and the scientific and medical understandings of safety or other risks to humans continue to evolve. If gene therapies prove to be unsafe for humans, we likely will need to curtail or eliminate our gene therapy development programs or gene therapy products in development or commercialization, if any.

We do not have any internal manufacturing capabilities and use third parties to manufacture our product candidates ~~is limited.~~on a contract or purchase order basis. Manufacturing issues, including technical or quality issues or issues with scaling up and building our capabilities for later-stage clinical manufacturing or for commercial manufacturing, may arise that could cause delays in our development programs or increase costs. ~~In addition, we~~We may experience delays in regulatory approval of our product candidates if we or our contract manufacturers do not satisfy applicable manufacturing regulatory requirements.

Our current product candidates, Zimura and Fovista, are each chemically-synthesized aptamers. In pursuing our business development activities, we could acquire or in-license a variety of types of product candidates, including small molecule drugs, protein drugs or biologics. Small molecule drugs are organic compounds of low molecular weight that are generally associated with ready availability of starting materials and ease of synthesis. In contrast, manufacturing for proteins and biologics is more complex, especially in large quantities. For example, biologic products must be made consistently and in substantial compliance with a clearly defined manufacturing process, and often must be manufactured under aseptic conditions.

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We do not have ~~any~~ internal manufacturing ~~capabilities~~facilities and ~~are dependent on~~use or plan to use outside contract manufacturers to manufacture IC-100, IC-200, Zimura, our HtrA1 inhibitors and any ~~of the~~other product candidates that we ~~would~~may acquire or ~~in-license as part~~in-license. We have a limited number of ~~pursuing our updated business plan.~~personnel hired to supervise these outside vendors. Manufacturing for these product candidates could be complicated or present novel technical challenges. Problems with the manufacturing process, even minor deviations from the ~~normal~~established process, could result in product defects or manufacturing failures that result in lot failures, product recalls, product liability claims or insufficient inventory. We may encounter problems achieving adequate quantities and quality of clinical-grade materials that meet FDA, EMA or other applicable standards or specifications with consistent and acceptable production yields and costs.

We currently rely upon a single third‑party manufacturer, Agilent Technologies, to supply us with the chemically synthesized aptamers comprising the API for both Zimura and Fovista and a different, single third‑party manufacturer, Ajinomoto Althea, to provide fill/finish services for both Zimura and Fovista. In order to obtain and maintain regulatory approval for Zimura or Fovista, our third‑party manufacturers will be required to consistently produce the API used in Zimura or Fovista in commercial quantities and

Table of specified quality and to execute fill/finish services on a repeated basis and document their ability to do so. If the third‑party manufacturers are unable to satisfy this requirement, our business would be materially and adversely affected. To date, we have not yet scaled up the manufacturing process for Zimura beyond the scale used for developmental clinical batches, nor have we validated the manufacturing process.Contents

These manufacturing processes and the facilities of our third‑party manufacturers, including our third‑party API manufacturer and our third‑party fill/finish service provider, are subject to inspection and approval by the FDA, referred to as a pre-approval inspection, before we can commence the commercial sale of any approved product candidate, and thereafter on an ongoing basis. Our third‑party API manufacturer has undergone only one pre-approval inspection by the FDA, and has not yet gone through a pre-approval inspection for Zimura or Fovista. Our third‑party fill/finish service provider is subject to FDA inspection from time to time. Failure by our third‑party manufacturers to pass such inspections and otherwise satisfactorily complete the FDA approval regimen with respect to our product candidates may result in delays in the approval of our applications for marketing approval in the event a recommendation to withhold is issued, as well as regulatory actions such as the issuance of FDA Form 483 notices of observations, warning letters or injunctions or the loss of operating licenses. Additionally, on October 22, 2014, the FDA issued its final guidance on the circumstances that constitute delaying, denying, limiting or refusing a drug inspection pursuant to Section 707 of the Food and Drug Administration Safety and Innovation Act of 2012. If any of our third‑party manufacturers are found to have delayed, denied, limited or refused a drug inspection, our API or drug product could be deemed adulterated. Based on the severity of the regulatory action, our clinical or commercial supply of API or our fill/finish services could be interrupted or limited, which could have a material adverse effect on our business.

Some of the standards of the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use, which establishes basic guidelines and standards for drug development in the United States, the European Union, Japan and other countries, do not apply to oligonucleotides, including aptamers. As a result, there are no established generally accepted manufacturing or quality standards for the production of Zimura or Fovista. Even though the FDA has reviewed the quality standards for Fovista used in our Phase 3 clinical program, the FDA has the ability to modify these standards at any time and foreign regulatory agencies may impose differing quality standards and quality control on the manufacture of Fovista. The lack of uniform manufacturing and quality standards among regulatory agencies may delay regulatory approval of Zimura or Fovista or any future product candidate.

In addition, in order to manufacture and supply any of our product candidates for later-stage clinical trials or on a commercial scale in the future, we will need to increase our manufacturing personnel and bolster our quality control and quality assurance ~~capabilities, including by augmenting our manufacturing processes and adding personnel.~~capabilities. We ~~also~~ may encounter problems hiring and retaining ~~the experienced specialist~~ scientific and manufacturing personnel needed to ~~operate~~oversee our manufacturing process, which could result in delays in our production or difficulties in maintaining compliance with applicable regulatory requirements. As we or any manufacturer we engage ~~scales-up~~scales up manufacturing of any ~~approved~~ product candidate, we may encounter unexpected issues relating to the manufacturing processes or the quality, purity or stability of the product, and we may be required to refine or alter our manufacturing processes to address these issues. Resolving these issues could result in significant delays and may result in significantly increased costs. If we underestimate the demand for an approved product, given the long lead times required to manufacture or obtain regulatory approvals for our products, we could potentially face commercial drug product supply shortages. If we experience significant delays or other obstacles in producing any approved product at commercial scale, our ability to market and sell any approved products may be adversely affected and our business could suffer.

The manufacturing processes and the facilities of our third-party manufacturers are subject to inspection and approval by the FDA, referred to as a pre-approval inspection, before we can commence the commercial sale of any approved product candidate, and thereafter on an ongoing basis. Our third-party drug substance manufacturer for Zimura has undergone only two pre-approval inspections by the FDA, and has not yet gone through a pre-approval inspection for Zimura. Failure by our third-party manufacturers to pass such inspections and otherwise satisfactorily complete the FDA approval regimen with respect to our product candidates may result in delays in the approval of our applications for marketing approval, as well as regulatory actions such as the issuance of FDA Form 483 notices of observations, warning letters or injunctions or the loss of operating licenses. If any of our third-party manufacturers are found to have delayed, denied, limited or refused a drug inspection, our drug substance or drug product could be deemed adulterated. Based on the severity of the regulatory action, our clinical or commercial supply of drug substance or drug product could be interrupted or limited, which could have a material adverse effect on our business.

Any problems in our manufacturing process or our third-party contract manufacturers’ facilities could make us a less attractive collaborator for potential partners, including larger pharmaceutical companies and academic research institutions,

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which could limit our access to additional attractive development programs. Problems in our manufacturing process or facilities also could restrict our ability to meet market demand for our products.

~~Even if any~~For a further discussion of the risks associated with our reliance on third-party manufacturers, see the risk factor herein entitled, "We contract with third parties for the manufacture of and for providing starting materials for our product candidates for preclinical development activities and clinical trials and expect to continue to do so in the future. This reliance on third parties increases the risk that we will not have sufficient quantities of our product candidates ~~receives marketing approval, such product candidate may fail to achieve the degree~~or products, which could delay, prevent or impair our development or commercialization efforts."

The manufacture of ~~market acceptance by physicians, patients, third~~‑~~party payors and others in the medical community necessary for commercial success and the market opportunity for any of our~~gene therapy products ~~and product candidates may be smaller than we estimate.~~

If any of our product candidates receive marketing approval, they may nonetheless fail to gain sufficient market acceptance by physicians, patients, third‑party payors and others in the medical community. For example, current treatments for wet AMD, including Lucentis, Eylea and low cost, off‑label use of Avastin, are well established in the medical community, and doctors may continue to rely upon these treatments without Zimura. If any of our product candidates, if approved, do not achieve an adequate level of acceptance, we may not generate significant product revenues and we may not become profitable. The degree of market acceptance of Zimura or any other product candidate that we may develop, if approved for commercial sale, will depend onis complex with a number of ~~factors, including:~~scientific and technical risks, some of which are common to the manufacture of drugs and biologics and others of which are unique to the manufacture of gene therapies. We have limited experience with gene therapy manufacturing and are dependent on our third-party contract manufacturers and sole source suppliers.

~~efficacy~~Gene therapy drug products are complex and difficult to manufacture. We believe that the high demand for clinical gene therapy material and a scarcity of potential ~~advantages compared~~contract manufacturers may cause long lead times for establishing manufacturing capabilities for gene therapy drug development activities. Even after a manufacturer is engaged, any problems that arise during manufacturing process development may result in unanticipated delays to ~~alternative treatments,~~our timelines, including ~~the existing standard~~delays attributable to securing additional manufacturing slots. There may also be long lead times to manufacture or procure starting materials such as plasmids and cell lines, especially for high-quality starting materials that are cGMP compliant. In particular, plasmids, raw materials and other starting materials for gene therapy manufacture are usually sole sourced, as there are a limited number of ~~care;~~

~~any restrictions in the label on the use~~qualified suppliers. The progress of our ~~products~~gene therapy programs is highly dependent on these suppliers providing us or our contract manufacturers with the necessary starting materials that meet our requirements in ~~combination with other medications;~~a timely manner. A failure to procure or a shortage of necessary starting materials likely would delay our manufacturing and development timelines.

~~any restrictions~~A number of factors common to the manufacturing of biologics and drugs could also cause production issues or interruptions for gene therapies, including raw material or starting material variability in ~~the label on the use~~terms of ~~our products by a subgroup of patients;~~

~~restrictions in the label on~~quality, cell line viability, productivity or stability issues, shortages of any ~~for~~kind, shipping, distribution and supply chain failures, growth media contamination, equipment malfunctions, facility contamination, labor problems, natural disasters, disruption in utility services, terrorist activities, or acts of god that are beyond our ~~combination therapy product candidates, such as Zimura , limiting their use in combination~~or our contract manufacturer's control. It is often the case that early stage process development is conducted with ~~particular standard of care drugs, such as a particular anti‑VEGF drug;~~

our and any commercialization partner’s ability to offer our products at competitive prices, particularly in light of the cost of any of our combination therapy product candidates in addition to the cost of the underlying standard of care drug;

~~availability of third‑party coverage and adequate reimbursement, particularly by Medicare given the target market for AMD indications for persons over age 55;~~

increasing reimbursement pressures on treating physicians due to the formation of accountable care organizations and the shift away from traditional fee‑for‑service reimbursement models to reimbursement based on quality of care and patient outcomes;

~~willingness of the target patient population to try new therapies and of physicians to prescribe these therapies, particularly in light of the existing available standard of care;~~

~~prevalence and severity of any side effects; and~~

~~whether competing products~~materials that are not manufactured using cGMP starting materials, techniques or other alternatives are more convenient or easier to administer, including whether co‑formulated alternatives, alternatives that can be co‑administered in a single syringe or alternatives that offer a less invasive method of administration than intravitreal injection come to market.

In addition, the potential market opportunity for any product candidate is difficult to estimate precisely. Our estimates of the potential market opportunity for our product candidates include several key assumptions based on our expectations of the safety and effectiveness of the relevant product candidate, our industry knowledge, industry publications, market response to marketed AMD drugs, third‑party research reports and other surveys. While we believe that our internal assumptions are reasonable, no independent source has verified such assumptions and any of these assumptions could prove to be inaccurate, and the actual market for such product candidates could be smaller than our estimates of our potential market opportunity.

With respect to our programs for orphan diseases, our understanding of both the number of people who have these diseases, as well as the subset of people with these diseases who have the potential to benefit from treatment with our product candidates, are based on estimates. These estimates may prove to be incorrect and new studies may reduce the estimated incidence or prevalence of these diseases. The number of patients in the United States, the European Union and elsewhere may turn out to be lower than expected, may not be otherwise amenable to treatment with our products or patients may become

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~~increasingly difficult~~processes and which are not subject to ~~identify~~the same level of analysis that would be required for clinical grade material. We may encounter difficulties in translating the manufacturing processes used to produce research grade materials to cGMP compliant processes, and ~~access, all~~any changes in the manufacturing process may affect the safety and efficacy profile of ~~which would adversely affect~~our product candidates. In addition, because early stage, pilot manufacturing is often done on a small scale, we may face challenges scaling up any early stage manufacturing to the scale necessary to support supply for clinical trials. In order to progress the development of IC-100, IC-200 or any other gene therapy product candidate we may in-license or acquire, we will need to devote significant time and financial resources to establishing manufacturing processes that are sufficient for IND-enabling preclinical toxicology studies as well as clinical supplies. If we are not able to establish gene therapy manufacturing or related processes in a manner required for further development of our gene therapy product candidates, our development plans may be delayed or stalled and our business ~~financial condition, results~~may be materially harmed.

Our experience manufacturing Zimura is limited. We and our third-party contract manufacturers have not scaled up or validated the manufacturing process for Zimura for later-stage clinical or commercial manufacturing. We are only in the early stages of ~~operations~~establishing manufacturing capabilities for our HtrA1 inhibitor program.

We currently use a single third-party manufacturer, Agilent Technologies, to supply us with the chemically synthesized drug substance for Zimura and ~~prospects.~~a different, single third-party manufacturer, Ajinomoto Bio-Pharma Services, to provide fill/finish services for Zimura. In order to obtain and maintain regulatory approval for Zimura, our third-party manufacturers will be required to consistently produce the drug substance used in Zimura in commercial quantities and of specified quality and to execute fill/finish services on a repeated basis and document their ability to do so. If the third-party manufacturers are unable to satisfy this requirement, our business would be materially and adversely affected. To date, we have not yet scaled up the manufacturing process for Zimura beyond the scale used for developmental clinical batches, nor have we validated the manufacturing process.

For our HtrA1 inhibitor program, we have recently engaged a CDMO to produce small quantities of the active pharmaceutical ingredient, or API, for our HtrA1 inhibitors. The time and efforts required for us to fully establish manufacturing capabilities for our HtrA1 inhibitor program may delay or impair our ability to develop this program in accordance with our expected timelines.

We face substantial competition, which may result in others developing or commercializing products before or more successfully than we do.

The development and commercialization of new drug products is highly competitive. We face competition with respect to our product candidates from major pharmaceutical companies, specialty pharmaceutical companies and biotechnology companies, as well as generic and biosimilar companies, worldwide. There are a number of pharmaceutical and biotechnology companies that are currently ~~market and sell products or are pursuing the development of~~developing product candidates for the treatment of ~~wet AMD, GA,~~RHO-adRP, LCA10, Stargardt disease ~~or other disease indications~~and GA, and there is at least one biotechnology company that is currently developing a product candidate for ~~which we may develop Zimura.~~the treatment of Best disease. Potential competitors also include academic institutions, government agencies and other public and private research organizations that conduct research, seek patent protection and establish collaborative arrangements for research, development, manufacturing and commercialization. Some of these competitive products and therapies are based on scientific approaches that are the same as or similar to our approach, and others are based on entirely different approaches. We also will face similar competition with respect to any ~~other products or~~ product candidates that we may seek to develop or commercialize in the ~~future~~future. In particular, many companies are pursuing gene therapy approaches for orphan and age-related retinal diseases.

Our commercial opportunity could be reduced or eliminated if one or more of our competitors develop and commercialize products that are more effective, safer, have fewer or less severe side effects, are more convenient to use or are less expensive than our product candidates. For example, the method of administration of Zimura, intravitreal injection, is commonly used to administer ophthalmic drugs for the treatment of ~~wet AMD, GA, Stargardt disease~~severe diseases and is generally accepted by patients facing the prospect of severe visual loss or ~~any~~blindness. A therapy that offers a less invasive method of administration, however, might have a competitive advantage over one administered by intravitreal injection, depending on the relative safety of the other ~~indication~~method of administration.

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Our competitors also may obtain FDA or other regulatory approval for their products more rapidly than we may ~~pursue.~~

~~Competitive considerations~~obtain approval for ~~Dry AMD and GA:~~

~~There are~~ours, which could result in our competitors establishing a number of products in preclinical research and clinical development by third parties to treat dry AMD. In general, these product candidates can be categorized based on their proposed mechanisms of action. The mechanisms of action for these product candidates include inflammation suppression, such as complement system inhibitors and corticosteroids, visual cycle modulators, antioxidants and neuroprotectants, cell and gene therapies and vascular enhancers. Based on publicly available information,strong market position before we are ~~aware that Genentech, Inc., a member of~~able to enter the Roche Group, Novartis AG and MorphoSys AG, Apellis Pharmaceuticals, Inc., Hemera Biosciences, Inc., Achillion Pharmaceuticals, Inc., Ra Pharmaceuticals, Inc. and Catalyst Biosciences, Inc. each have complement inhibitorsrelevant market. Furthermore, our ability to compete may be affected in development, the most advanced of which is Genentech’s humanized Fab fragment targeting complement factor D, which is at a different part of the complement cascade than complement factor C5. Genentech announced negative data from the first of two Phase 3 trials during the third quarter and is expected release initial top-line data from the remaining Phase 3 trialmany cases by ~~the end of 2017. In addition, Apellis announced positive Phase 2b results for its pegylated, synthetic peptide targeting complement factor C3 for the treatment of GA and has announced plans~~insurers or other third-party payors, particularly Medicare, seeking to initiate a Phase 3 program during 2018. If Genentech's remaining Phase 3 trial for its complement factor D product candidate is successful or if Apellis's Phase 3 program for its complement factor C3 product candidate is successful, it is likely that one of these competitors may obtain marketing approval for such product candidate in advance of when we could reasonably expect marketing approval for Zimura in GA, if at all. Moreover, based on publicly available information, we are aware that several other companies have announced development programs for the treatment of dry AMD targeting different mechanisms of action outside of the complement cascade.

~~Competitive considerations for Stargardt disease:~~

There are a number of products in preclinical research and clinical development by third parties to treat Stargardt disease. Based on publicly available information, we are aware that Sanofi, Acucela Inc., Alkeus Pharmaceuticals, Inc., Vision Medicines, Inc. and Lin BioScience, Inc. each have development programs in Stargardt disease. Four of these programs, Acucela, Alkeus, Vision Medicines and Lin BioScience, are exploringencourage the use of oral therapeutics, while Sanofi, with technology provided by Oxford BioMedica plc, is using a gene therapy approach. Acucela’s, Alkeus’s and Sanofi’s product candidates are each in Phase 2 development.less expensive or more convenient products.

In the case of orphan diseases such as RHO-adRP, Best disease and other bestrophinopathies, LCA10 or Stargardt disease, should we be successful in development, our commercialization efforts may rely on non-patent market exclusivity periods under the Orphan Drug Act and the Hatch-Waxman Act. The Orphan Drug Act only provides exclusivity periods for the specific drug granted orphan drug designation for a specific indication. In addition, there are limited circumstances under each of the Orphan Drug Act and the Hatch-Waxman Act that could result in our loss of data and marketing exclusivity, which could allow a competitor to enter the market. Failure to maintain either data or market exclusivity period ~~would~~could have a material adverse effect on our ability to commercialize our product candidates.

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~~Competitive considerations for wet AMD:~~

There are a number of products in preclinical research and clinical development by third parties to treat wet AMD. Based on publicly available information, we are aware that multiple mechanisms of action are in clinical or pre-clinical development for wet AMD, including Angiopoietin-2 inhibitors, tyrosine kinase inhibitors, integrin inhibitors, novel VEGF inhibitors and complement inhibitors, as well as a few remaining PDGF inhibitors. Within the complement cascade, we are aware that Apellis is planning a Phase 2 clinical trial with their C3 inhibitor in combination with anti-VEGF therapy. Moreover, based on publicly available information, we are aware that several companies and research organizations are pursuing treatments targeting other molecular targets, potential gene therapy treatments and stem cell transplant treatments for the treatment of wet AMD. In addition, other companies are undertaking efforts to develop technologies to allow for topical dosing of anti-VEGF agents through eye-drops or to allow for a less frequent dosing schedule than the dosing schedule currently in use for standard of care anti-VEGF drugs.

In addition, our commercial opportunity could be reduced or eliminated if one or more of our competitors develop and commercialize products that are more effective, safer, have fewer or less severe side effects, are more convenient to use or are less expensive than our product candidates. The commercial opportunity for Zimura in wet AMD in particular also could be reduced or eliminated if our competitors develop and commercialize products that reduce or eliminate the use of anti‑VEGF drugs for the treatment of patients with wet AMD. Our competitors also may obtain FDA or other regulatory approval for their products more rapidly than we may obtain approval for ours, which could result in our competitors establishing a strong market position before we are able to enter the relevant market.

Furthermore, our ability to compete may be affected in many cases by insurers or other third‑party payors, particularly Medicare, seeking to encourage the use of less expensive or more convenient products. We expect that if Zimura is approved for combination therapy for the treatment of wet AMD, the cost of combination treatment would be higher than the cost of treatment of wet AMD with Lucentis, Eylea or particularly Avastin monotherapy. Insurers and other third‑party payors may encourage the use of anti‑VEGF drugs as monotherapy and discourage the use of Zimura in combination with these drugs. This could limit sales of Zimura for this indication.

Many of our competitors have significantly greater financial and human resources and expertise in research and development, manufacturing, preclinical testing, conducting clinical trials, obtaining regulatory approvals and marketing approved products than we do. Smaller and other early stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established companies. These third parties compete with us in recruiting and retaining qualified scientific and management personnel, establishing clinical trial sites and patient enrollment for clinical trials, as well as in acquiring technologies complementary to, or necessary for, our development programs.

Based on publicly available information, we are aware of the following research and development programs that may be competitive with programs we are pursuing. Other competitive programs may exist of which we are not aware.

Competitive considerations for RHO-adRP:

There are a number of products in preclinical research by third parties to treat RHO-adRP. We are aware that multiple academic institutions have early stage gene therapy development programs in RHO-adRP. In addition, Nightstar Therapeutics plc has a preclinical AAV gene therapy program in RHO-adRP and ProQR Therapeutics N.V. is developing an early stage RNA-based therapeutic for RHO-adRP.

Competitive considerations for Best disease and other bestrophinopathies:

We are aware that Nightstar Therapeutics plc has a preclinical AAV gene therapy program in Best disease.

Competitive considerations for LCA10:

We are aware that Editas Medicine has a CRISPR gene editing program for LCA10, an IND for which was submitted in late 2018, ProQR Therapeutics N.V. is developing an RNA-based therapeutic for LCA10 that is currently in clinical development, ~~programs.~~Generation Bio Co. has a preclinical program that utilizes ceDNA technology to target LCA10 and Oxford Biomedica plc is developing a lentiviral gene therapy program for LCA10 that is in preclinical development. In addition, several academic institutions have preclinical programs in LCA10.

Competitive considerations for Stargardt disease:

There are a number of products in preclinical research and clinical development by third parties to treat Stargardt disease. We are aware that Sanofi, Acucela Inc., Alkeus Pharmaceuticals, Inc., Vision Medicines, Inc., Lin BioScience, Inc., Nightstar Therapeutics plc, ProQR Therapeutics N.V., Spark Therapeutics and Generation Bio Co. each have research or development programs in Stargardt disease. Four of these programs, Acucela, Alkeus, Vision Medicines and Lin BioScience, are exploring the use of oral therapeutics, while Sanofi, with technology provided by Oxford BioMedica plc, Nightstar and Spark are each using a gene therapy approach and ProQR is using an RNA based approach. Acucela’s product candidate is in Phase 3 development while Alkeus’s and Sanofi’s product candidates are each in Phase 2 development. Spark's program is in the research phase. In addition, several academic organizations have early stage programs in Stargardt disease.

Competitive considerations for Dry AMD and GA:

There are a number of products in preclinical research and clinical development by third parties to treat dry AMD, including several that are in development for GA secondary to dry AMD. In general, these product candidates can be categorized based on their proposed mechanisms of action. The mechanisms of action for these product candidates

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include inflammation suppression, such as complement system inhibitors and corticosteroids, visual cycle modulators, antioxidants and neuroprotectants, cell and gene therapies and vascular perfusion enhancers. We are aware that Apellis Pharmaceuticals, Inc., Roche AG, Novartis AG and MorphoSys AG, Hemera Biosciences, Inc., Gyroscope Therapeutics, Achillion Pharmaceuticals, Inc., and Catalyst Biosciences, Inc. each have complement inhibitors in development for dry AMD. We believe that the most advanced of these programs is Apellis's pegylated, synthetic peptide targeting complement protein C3. Following positive Phase 2 results for its C3 complement inhibitor product candidate, Apellis announced in September 2018 that it had dosed the first patient in a Phase 3 program for this product candidate. If Apellis's Phase 3 program for its C3 complement inhibitor product candidate is successful, it is likely that Apellis may obtain marketing approval for its product candidate in advance of when we could reasonably expect marketing approval for Zimura in GA or a product candidate from our HtrA1 inhibitor program in GA, if at all. Moreover, we are aware that several other companies have announced development programs for the treatment of dry AMD or GA targeting different mechanisms of action outside of the complement system.

If we are unable to establish sales, marketing and distribution capabilities or enter into sales, marketing and distribution agreements with third parties, we may not be successful in commercializing any of our product candidates that we develop if and when any such product candidate is approved.

As a company, we have no experience in the sale, marketing or distribution of pharmaceutical products. We currently do not have any sales, marketing or distribution infrastructure. To achieve commercial success for any approved product, we must either develop a sales, marketing and distribution organization or outsource those functions to third parties. We expect that our commercial strategy for any of our product candidates, including whether to retain commercial rights and market and sell the product candidate ourselves or to utilize collaboration, distribution or other marketing arrangements with third parties, would be determined based on a variety of factors, including the size and nature of the patient population, the disease area, the particular ~~indication,~~indications for which the ~~territory~~product candidate is approved, the territories in which the product candidate may be marketed and the commercial potential for such product candidate. Our gene therapy programs are currently being developed for orphan IRDs with a limited number of affected individuals. In contrast, we are developing Zimura and our HtrA1 inhibitor program for GA secondary to dry AMD, which is a condition affecting a relatively large number of individuals. If any of our product candidates are approved, the size and nature of the affected patient population will be an important factor in our commercial strategy. In addition, our commercial strategy would vary depending on whether the disease is typically treated by general ophthalmology practitioners, specialists, such as retinal specialists, or ~~sub-specialists.~~sub-specialists, such as retinal specialists with particular expertise in IRDs.

There are risks involved with establishing our own sales, marketing and distribution capabilities and entering into arrangements with third parties to perform these services. For example, recruiting and training a sales force is expensive and time consuming and could delay any product launch. If the commercial launch of a product candidate for which we recruit a sales force and establish marketing and distribution capabilities is delayed or does not occur for any reason, we would have prematurely or unnecessarily incurred these commercialization expenses. This may be costly, and our investment would be lost if we cannot retain or reposition our sales and marketing personnel.

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

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

the inability of sales personnel to obtain access to adequate numbers of physicians who may prescribe our products;

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

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

If we enter into arrangements with third parties to perform sales, marketing and distribution services, our product revenues and our profitability, if any, are likely to be lower than if we were to market, sell and distribute ourselves any products that we develop. In addition, we may not be successful in entering into arrangements with third parties to sell, market and distribute our product candidates or may be unable to do so on terms that are favorable to us. We likely will have little control over such third parties, and any of them may fail to devote the necessary resources and attention to sell and market our products effectively. If we do not establish sales, marketing and distribution capabilities successfully, either on our own or in collaboration with third parties, we would not be successful in commercializing our product candidates.

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Even if any of our product candidates receives marketing approval, such product candidate may fail to achieve the degree of market acceptance by physicians, patients, third-party payors and others in the medical community necessary for commercial success and the market opportunity for any of our products and product candidates may be smaller than we estimate.

The degree of market acceptance of any product candidate that we are developing or we may develop, if approved for commercial sale, will depend on a number of factors, including:

efficacy and potential advantages compared to alternative treatments, including the existing standard of care;

any restrictions in the label on the use of our products in combination with other medications or with certain devices;

any restrictions in the label on the use of our products by a subgroup of patients;

restrictions in the label imposing a waiting period in between intravitreal or subretinal injections;

our and any commercialization partner’s ability to offer our products at competitive prices;

availability of governmental and third-party payor coverage and adequate reimbursement;

increasing reimbursement pressures on treating physicians due to the formation of accountable care organizations and the shift away from traditional fee-for-service reimbursement models to reimbursement based on quality of care and patient outcomes;

willingness of the target patient population to try new therapies and of physicians to prescribe these therapies, particularly in light of the existing available standard of care or to the extent our product candidates require invasive procedures for administration, such as subretinal surgery;

prevalence and severity of any side effects or perceived safety concerns, especially for new therapeutic modalities such as gene therapy; and

whether competing products or other alternatives are more convenient or easier to administer, including whether co-formulated alternatives, alternatives that can be co-administered in a single syringe or alternatives that offer a less invasive method of administration than intravitreal injection or subretinal injection come to market.

For each of our Zimura trials where patients will receive multiple intravitreal injections on the same day, we have provided for a delay in the second intravitreal injection to minimize the risk of an unacceptable increase in intraocular pressure as a result of the volume of the multiple injections. In addition, certain of the Zimura dosing regimens we are evaluating require injections more frequently than once per month. If Zimura receives marketing approval for a particular indication and the approved label requires a waiting period between injections administered on the same day or a dosing regimen that requires multiple office visits per month, the potential market opportunity for Zimura may be limited to the extent that physicians and patients find such a waiting period or dosing regimen unacceptable.

In addition, the potential market opportunity for any product candidate is difficult to estimate precisely. Our estimates of the potential market opportunity for our product candidates include several key assumptions based on our expectations of the safety and effectiveness of the relevant product candidate, our industry knowledge, industry publications, market response to Spark Therapeutics's Luxturna® and anti-VEGF agents currently approved for treatment of wet AMD, third-party research reports and other surveys. While we believe that our internal assumptions are reasonable, no independent source has verified such assumptions and any of these assumptions could prove to be inaccurate, and the actual market for such product candidates could be smaller than our estimates of our potential market opportunity.

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Even if we are able to commercialize any of the product candidates that we may develop, the product may become subject to unfavorable pricing regulations, ~~third~~‑~~party~~pricing dynamics, third-party reimbursement practices or healthcare reform initiatives, which would harm our business.

The regulations that govern marketing approvals, pricing and reimbursement for new drug products vary widely from country to country. Health care reform, including increasing scrutiny of drug prices, is an issue of intense political focus, particularly in the United States. Current and future legislation may significantly change the approval requirements in ways that could involve additional costs and cause delays in obtaining approvals or in ways that could alter the mechanism by which pharmaceutical prices are negotiated or otherwise determined. ~~Some~~Many countries outside the United States require approval of the sale price of a drug before it can be ~~marketed.~~marketed, and to apply for and obtain such an approval in certain countries, we or a commercialization partner may be required to conduct a clinical trial that compares the cost-effectiveness of our product candidate to other available therapies. In many countries, the pricing review period begins after marketing or product licensing approval is granted. In some foreign markets, prescription pharmaceutical pricing remains subject to continuing governmental control or negotiation even after initial approval is granted. As a result, we might obtain marketing approval for a product in a particular country, but then be subject to price regulations that delay our or any commercialization partner’s commercial launch of the product, possibly for lengthy time periods, ~~and~~which would negatively impact the revenues we are able to generate from the sale of the product in that country. Adverse pricing limitations may hinder our ability to recoup our investment in one or more product candidates, even if our product candidates obtain marketing approval and are widely accepted and prescribed or used by physicians.

In addition, even in countries where pharmaceuticals are not subject to strict pricing regulations through a governmental review and approval process, we may nonetheless face an unfavorable pricing environment as a result of political pressure or market dynamics. Because there is only one FDA-approved gene replacement therapy product, which began commercial sales in 2018, the pricing environment for gene therapies is in the very early stages of its development. Gene therapies are generally intended to be one-time treatments or, at a minimum, to provide a benefit over an extended period lasting several years. If we are successful in obtaining marketing approval for any of our gene therapy product candidates, we will need to convince third-party payors of the value that our gene therapy product offers. Third-party payors may be unwilling to accept substantial upfront costs for a therapy where the benefits are realized over a period of years during which the patient may no longer be enrolled in the payor's plan. Furthermore, the pricing for products intended to treat orphan diseases in particular may be perceived as too high to be justified. The perceived high cost for pharmaceutical products to treat orphan diseases may attract increased political and public scrutiny. Moreover, if we obtain marketing approval for a product candidate, such as Zimura, in more than one indication, including, for example in an orphan indication such as STGD1 and a non-orphan indication such as GA secondary to dry AMD, such a product candidate likely would only be sold at one price in any given country, regardless of the indications for which it is prescribed. This dynamic may result in our charging a price that does not generate profits in each indication for which the product is approved.

Our ability and the ability of any commercialization partner to commercialize a product candidate successfully also will depend in part on the extent to which reimbursement for these products and related treatments will be available from government health ~~administration~~ authorities, private health insurers and other organizations. Government authorities and ~~third‑party~~third-party payors, such as private health insurers and health maintenance organizations, decide which medications they will pay for and establish reimbursement levels. A major trend in the U.S. healthcare industry and elsewhere is cost containment. Government authorities and ~~third‑party~~third-party payors, particularly Medicare, have attempted to control costs by limiting coverage and the amount of reimbursement for particular medications and encouraging the substitution of lower cost or generic products. Pricing pressures recently experienced by the pharmaceutical industry may be further exacerbated by legislative and policy changes under consideration by the Trump ~~Administration.~~Administration and many states. For example, the ~~new~~Trump Administration has expressed an interest in authorizing and/or directing the Center for Medicare & Medicaid Service or other agencies of the U.S. government to negotiate prices for drugs covered by Medicare directly with pharmaceutical companies. If this were to occur, especially for ~~wet~~ AMD drugs where a large portion of the patient population is over the age of 65 and is therefore covered by Medicare, there could be significant downward pressure on prices charged, not only for patients covered by Medicare, but also for patients covered by private insurers who may follow the government’s lead on price. Moreover, increasingly, ~~third‑party~~third-party payors are requiring that drug companies provide them with predetermined discounts from list prices and are challenging the prices charged for ~~medical~~pharmaceutical products. We cannot be sure that coverage and reimbursement will be available for any product that we commercialize or any commercialization partner commercializes on our behalf, and, even if these are available, the level of reimbursement may not be satisfactory.

Reimbursement may affect the demand for, or the price of, any product candidate for which we obtain marketing approval. Obtaining and maintaining adequate reimbursement for our products may be particularly difficult because of the

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higher prices often associated with drugs administered under the supervision of a physician and because, in the case of Zimura for the treatment of wet AMD, our drug would be administered in combination with other drugs that may carry high prices. In addition, physicians, patients and third‑party payors may be sensitive to the addition of the cost of Zimura to the cost of treatment with anti‑VEGF drugs for the treatment of wet AMD.physician. We or any commercialization partner may be required to conduct expensive pharmacoeconomic studies to justify coverage and reimbursement or the level of

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reimbursement relative to other therapies ~~including in~~that may be on the ~~case of Zimura for the treatment of wet AMD, relative to monotherapy with anti‑VEGF drugs.~~market. If coverage and adequate reimbursement are not available or reimbursement is available only toat limited levels, we may not be able to successfully commercialize any product candidate for which we obtain marketing approval.

There may be significant delays in obtaining reimbursement for newly approved drugs, and coverage may be more limited than the purposes for which the drug is approved by the FDA or similar regulatory authorities outside the United States. Moreover, eligibility for reimbursement does not imply that any drug will be paid for in all cases or at a rate that covers our costs, including research, development, manufacture, sale and distribution. Interim reimbursement levels for new drugs, if applicable, may also not be sufficient to cover our costs and may not be made permanent. Reimbursement rates may vary according to the use of the drug and the clinical setting in which it is used, may be based on reimbursement levels already set for lower cost drugs, and may be incorporated into existing payments for other services. Net prices for drugs may be reduced by mandatory discounts or rebates required by government healthcare programs or private payors and by any future relaxation of laws that presently restrict imports of drugs from countries where they may be sold at lower prices than in the United States, a policy that President Trump ~~has~~and certain members of the U.S. Congress have expressed interest in pursuing. ~~Third‑party~~Third-party payors often rely upon Medicare coverage policy and payment limitations in setting their own reimbursement policies. Our and any commercialization partner’s inability to promptly obtain coverage and profitable payment rates from both ~~government‑funded~~government-funded and private payors for any approved products that we develop could have a material adverse effect on our operating results, our ability to raise capital needed to commercialize products and our overall financial condition.

~~Governments outside~~For a further discussion of health care reform and other political factors affecting drug prices, see the ~~United States tend~~risk factor herein entitled "Current and future legislation and regulations may increase the difficulty and cost for us and any future collaborators to ~~impose strict price controls, which may adversely affect our revenues, if any.~~

The pricing of prescription pharmaceuticals is subject to governmental control outside of the United States. In these countries, pricing negotiations with governmental authorities can take considerable time after the receipt ofobtain marketing approval ~~for a product. To obtain reimbursement or pricing approval in some countries,~~of and commercialize our product candidates and affect the prices we or ~~a commercialization partner~~they may ~~be required to conduct a clinical trial that compares the cost‑effectiveness of our product candidate to other available therapies. If reimbursement of our~~charge for such products, ~~is unavailable or limited in scope or amount, or~~when and if ~~pricing is set at unsatisfactory levels, our business could be harmed, possibly materially.~~approved."

Product liability lawsuits against us or any future commercialization partner could divert resources, cause us to incur substantial liabilities and limit commercialization of any products that we may develop or in‑~~license.~~in-license.

We face an inherent risk of product liability exposure related to the testing of any product candidate that we develop in human clinical trials, and we and any future commercialization partner will face an even greater risk if we commercially sell any products that we develop or in‑license. Because our Zimura wet AMD and ICPV trials involve or will involve the administration of Zimura in combination with an anti‑VEGF drug, we also face an inherent risk of product liability exposure related to the testing of such anti‑VEGF drug.develop. If we become subject to or otherwise cannot successfully defend ourselves against claims that ~~our product candidates, anti‑VEGF drugs administered in combination with~~ our product candidates or our products caused injuries, we will incur substantial liabilities. Regardless of merit or eventual outcome, liability claims may result in:

decreased demand for any product candidates or products that we may develop or ~~in‑license;~~in-license;

injury to our reputation and significant negative media attention;

withdrawal of clinical trial participants;

significant costs to defend the related litigation;

substantial monetary awards to trial participants or patients;

loss of revenue;

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reduced time and attention of our management to pursue our business strategy; and

the inability to commercialize any products that we may develop or ~~in‑license.~~in-license.

We currently hold $10.0 million in product liability insurance coverage in the aggregate, with a per incident limit of $10.0 million, which may not be adequate to cover all liabilities that we may incur. We will need to increase our insurance coverage when and if we begin commercializing an approved product. Insurance coverage is increasingly expensive. We may not be able to maintain insurance coverage at a reasonable cost or in an amount adequate to satisfy any liability that may arise. In addition, if a commercialization or collaboration partner were to become subject to product liability claims or were unable to successfully defend themselves against such claims, any such commercialization or collaboration partners could be more likely to terminate such relationship with us and therefore substantially limit the commercial potential of our products.

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Risks Related to Our Dependence on Third Parties

We contract with third parties for the manufacture of and for providing starting materials for our product candidates for preclinical development activities and clinical trials and expect to continue to do so in the future. This reliance on third parties increases the risk that we will not have sufficient quantities of our product candidates or products, which could delay, prevent or impair our development or commercialization efforts.

We do not currently own or operate manufacturing facilities for the production of clinical or commercial quantities of any of our product candidates and have a limited number of personnel hired to supervise outside contract manufacturers. We currently rely upon and expect to continue to rely upon third-party contract manufacturers to manufacture preclinical and clinical supplies of product candidates we are developing or may develop and commercial supplies of products if and when approved for marketing by applicable regulatory authorities. Furthermore, we and our contract manufacturers currently rely upon, and for the foreseeable future expect to continue to rely upon, sole-source suppliers of certain raw materials, plasmids and other specialized components of production used in the manufacture and fill/finish of our product candidates.

We have engaged a gene therapy CDMO for preclinical and Phase 1/2 clinical supply of IC-100 and IC-200. For our HtrA1 inhibitor program, we have recently engaged a CDMO to produce small quantities of the API for our HtrA1 inhibitors.

We currently rely exclusively upon, and purchase on a purchase order basis, a single third-party manufacturer to provide Zimura drug substance and a different single third-party manufacturer to provide fill/finish services for Zimura. We do not currently have any contractual commitments for the supply of Zimura drug substance. We also do not currently have arrangements in place for redundant supply or a second source for drug substance for Zimura or a second source for fill/finish services for Zimura. We purchase the polyethylene glycol, or PEG, reagent used to modify the chemically synthesized aptamer in Zimura on a purchase order basis from a single third-party supplier. We do not currently have any contractual commitments for supply of the PEG reagent we use for Zimura. The prices for manufacturing activities that are not yet contractually committed may vary substantially over time and adversely affect our financial results.

Our current and anticipated future dependence upon others for the manufacture of the product candidates that we are developing or may develop may adversely affect our business plan and future growth. For example, any performance failure or differing priorities on the part of our existing or future manufacturers could delay preclinical or clinical development or marketing approval of our product candidates. Our dependence on third party manufacturers may limit our ability to commercialize on a timely and competitive basis any products that receive marketing approval.

If any of our third-party manufacturers, fill/finish providers or sole-source suppliers fail to fulfill our purchase orders, or if any of these manufacturers or suppliers should become unavailable to us for any reason, including as a result of capacity constraints, differing priorities, regulatory compliance issues, financial difficulties or insolvency, we believe that there are a limited number of potential replacement manufacturers or sole source suppliers, and we likely would incur added costs and delays in identifying or qualifying such replacements. We may be unable to establish agreements with such replacement manufacturers, fill/finish providers or sole-source suppliers or to do so on acceptable terms.

In addition, to the extent that we or our third party manufacturers rely on materials that are sourced outside the United States, our supplier relationships could be interrupted due to international supply disruptions, including those caused by geopolitical and other issues. For example, trade disputes, trade negotiations or the imposition of tariffs between the United States and its trading partners could cause delays or disruptions in our supply of starting materials for our product candidates.

Reliance on third-party manufacturers entails additional risks, including:

our product candidates may compete with other product candidates and products for access to a limited number of suitable manufacturing facilities that operate under cGMP conditions;

reliance on the third party for regulatory compliance, quality assurance and quality control;

the possible breach of the manufacturing agreement by the third party;

the possible misappropriation of our proprietary information, including our trade secrets and know-how; and

the possible termination or nonrenewal of the agreement by the third party at a time that is costly or inconvenient for us.

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Third-party manufacturers may not be able to comply with cGMP regulations or similar regulatory requirements outside the United States. Our failure, or the failure of our third-party manufacturers, to comply with applicable regulations could result in sanctions being imposed on us, including clinical holds, fines, injunctions, civil penalties, delays, suspension or withdrawal of approvals, license revocation, seizures or recalls of product candidates or products, operating restrictions and criminal prosecutions, any of which could significantly and adversely affect supplies of our products and harm our business and results of operations.

We rely upon third parties in conducting our preclinical development activities and clinical trials, and those third parties may not perform satisfactorily, including failing to meet deadlines for the completion of such activities.

We have in the past and expect in the future to rely upon third parties, such as contract research organizations, or CROs, clinical data management organizations, biostatisticians, academic research collaborators, medical institutions (including reading centers) and clinical investigators, in conducting our preclinical testing and clinical trials for our product candidates. We or these third parties may terminate their engagements with us at any time for a variety of reasons, including a failure to perform by the third parties. If we need to enter into alternative arrangements, our product development activities could potentially be delayed and could potentially be very costly.

Our reliance on these third parties for preclinical testing and clinical development activities reduces our control over these activities but does not relieve us of our responsibilities. For example, we remain responsible for ensuring that each of our clinical trials is conducted in accordance with the general investigational plan and protocols for the trial. Moreover, the FDA requires us to comply with GCPs for conducting, recording and reporting the results of clinical trials to assure that data and reported results are credible and accurate and that the rights, integrity and confidentiality of trial participants are protected. We also are required to register ongoing clinical trials and post the results of completed clinical trials on a government-sponsored database within specified timeframes. Failure to do so can result in fines, adverse publicity and civil and criminal sanctions.

If these third parties do not successfully carry out their contractual duties, meet expected deadlines or conduct our clinical trials in accordance with regulatory requirements or our stated protocols, we would not be able to obtain, or may be delayed in obtaining, marketing approvals for our product candidates and would not be able to, or may be delayed in our efforts to, successfully commercialize our product candidates. Furthermore, these third parties may also have relationships with other entities, some of which may be our competitors.

We also rely upon other third parties to store, package, label and distribute drug supplies for our clinical trials and to store materials and drug substance for our preclinical development activities. Any performance failure on the part of these third parties could delay preclinical development, clinical development or marketing approval of our product candidates or commercialization of our products and adversely affect our results of operations.

We rely on third-party researchers to advance our sponsored research programs. These arrangements may not ultimately yield any promising product candidates for preclinical or clinical development. We may not be able to fully realize the benefits of any intellectual property generated by these arrangements.

Part of our strategy involves collaborative sponsored research to be performed by third-party research institutions. Although we seek to direct this research and advise on the design of these projects as well as critical development decisions, this research is being performed by individuals who are not our employees and the timeline and quality of the research efforts are outside of our direct control. Academic investigators and other researchers may have different priorities than we do as a biopharmaceutical drug development company. Confidential information and new inventions derived from these research efforts may be disclosed through publications or other means prior to our being able to protect such intellectual property through the filing of patent applications. Our third-party research partners may not be able to obtain or maintain full ownership of inventions that are derived from the research or associated rights, which may limit their ability to provide us with a license to all relevant intellectual property on terms and conditions that are acceptable to us. Even if our collaborative research efforts yield promising results or new technological advances, they may not ultimately result in our being able to protect, develop or exploit the resulting intellectual property.

If we are not able to establish ~~additional, future~~ collaborations to advance our development programs, we may have to alter our development and commercialization plans.

The development and potential commercialization of our product candidates is likely to require substantial additional cash to fund expenses. In addition, the commercialization of a product candidate in markets outside of the United States requires regulatory expertise and commercial capabilities that are specific to the local market. For some of our product

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candidates, including Zimura if data for our ongoing clinical trials are positive, we may ~~decide~~seek to collaborate with pharmaceutical and biotechnology companies for the development and potential commercialization of those product candidates.

We face significant competition in seeking appropriate collaborators. Whether we reach a definitive agreement for a collaboration will depend, among other things, upon our assessment of the collaborator’s resources and expertise, the terms and conditions of the proposed collaboration and the proposed collaborator’s evaluation of a number of factors. Those factors may include the design or results of clinical trials, the likelihood of approval by the FDA or similar regulatory authorities outside the United States, the potential market for the subject product candidate, the costs and complexities of manufacturing and delivering such product candidate to patients, the potential of competing products, the existence of uncertainty with respect to our ownership of technology, which can exist if there is a challenge to such ownership without regard to the merits of the challenge, and industry and market conditions generally. The collaborator may also consider alternative product candidates or technologies for similar indications that may be available to collaborate on and whether such collaboration could be more attractive than the one with us for our product candidate. We may also be restricted under future license agreements from entering into agreements on certain terms with potential collaborators. Collaborations are complex and ~~time‑consuming~~time-consuming to negotiate and document. In addition, there have been a significant number of recent business combinations among ~~large~~ pharmaceutical and biotechnology companies that have resulted in a reduced number of potential future collaborators.

If we are unable to reach agreements with suitable collaborators on a timely basis, on acceptable terms, or at all, we may have to curtail the development of a product candidate, 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. If we elect to fund and undertake development or commercialization activities on our own, we may need to obtain additional expertise and additional capital, which may not be available to us on acceptable terms or at all. If we fail to enter into collaborations and do not have sufficient funds or expertise to undertake the necessary development and commercialization activities, we may not be able to further develop ~~our~~those product candidates or bring them to market and generate product revenue.

We may enter into collaborations with third parties for the development or commercialization of our product candidates. These collaborations carry numerous risks. If any of our collaborations are not successful, we may not be able to capitalize on the market potential of these product candidates.

We may utilize a variety of types of collaboration, distribution and other marketing arrangements with third parties to develop or commercialize our product candidates, either in the United States, or in markets outside the United States. We also may seek ~~third‑party~~third-party collaborators for development and commercialization of other product candidates we may develop. Our likely collaborators for any sales, marketing, distribution, development, licensing or broader collaboration arrangements include large and ~~mid‑size~~mid-size pharmaceutical companies, regional and national pharmaceutical companies and biotechnology companies. If we do enter into any additional arrangements with third parties in the future, we would likely have limited control over the amount and timing of resources that our collaborators dedicate to the development or commercialization of our product candidates. Our ability to generate revenues from these arrangements will depend on our collaborators’ abilities and efforts to successfully perform the functions assigned to them in these arrangements.

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Collaborations involving our product candidates could pose numerous risks to us, including the following:

collaborators, including marketing and distribution collaborators, have significant discretion in determining the efforts and resources that they will apply to these collaborations and may not perform their obligations as expected;

collaborators may deemphasize or not pursue development and commercialization of our product candidates or may elect not to continue or renew development or commercialization programs based on clinical trial results, changes in the collaborators’ strategic focus, changes in product candidate priorities or available funding or changes in priorities as a result of a merger, acquisition or other corporate restructuring or transaction;

collaborators may delay clinical trials, provide insufficient funding for a clinical trial program, stop a clinical trial or abandon a product candidate, repeat or conduct new clinical trials or require a new formulation of a product candidate for clinical testing;

collaborators could independently develop, or develop with third parties, products that compete directly or indirectly with our products or product candidates if the collaborators believe that competitive products are more likely to be successfully developed or can be commercialized under terms that are more economically attractive than ours;

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we could grant exclusive rights to our collaborators, which would prevent us from collaborating with others;

disagreements or disputes with collaborators, including disagreements or disputes over proprietary rights, contract interpretation or the preferred course of development, might cause delays or termination of the research, development or commercialization of products or product candidates, might lead to additional responsibilities for us with respect to product candidates or might result in litigation or arbitration, any of which would divert management attention and resources, be ~~time‑consuming~~time-consuming and be expensive;

~~collaborators with marketing and distribution rights to one or more products may not commit sufficient resources to the marketing and distribution of such product or products;~~

collaborators may not properly maintain or defend our intellectual property rights, may infringe the intellectual property rights of third parties, may misappropriate our trade secrets or may use our proprietary information in such a way as to invite litigation that could jeopardize or invalidate our intellectual property or proprietary information or expose us to litigation and potential liability; and

collaborations may be terminated for the convenience of the collaborator, our breach of the terms of the collaboration or other reasons and, if terminated, we may need to raise additional capital to pursue further development or commercialization of the applicable product candidates.

If a collaborator of ours were to be involved in a business combination or other transaction, the foregoing risks would be heightened, and the business combination or transaction may divert attention or resources or create competing priorities. The collaborator may delay or terminate our product development or commercialization program. If one of our collaborators terminates its agreement with us, we could find it more difficult to attract new collaborators and the perception of our company ~~in the business and financial communities~~ could be adversely affected.

Collaboration agreements may not lead to development or commercialization of product candidates in the most efficient manner or at all.

We ~~rely upon third parties in conducting our clinical trials, and those third parties may not perform satisfactorily, including failing to meet deadlines for the completion of such trials.~~

We have in the past and expect in the future to rely upon third parties, such as CROs, clinical data management organizations, medical institutions (including reading centers) and clinical investigators, in conducting our clinical trials for our product candidates. We or these third parties may terminate their engagements with us at any time for a variety of reasons, including a failure to perform by the third parties. If we need to enter into alternative arrangements, our product development activities could potentially be delayed and could potentially be very costly.

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Our reliance on these third parties for clinical development activities reduces our control over these activities but does not relieve us of our responsibilities. For example, we remain responsible for ensuring that each of our clinical trials is conducted in accordance with the general investigational plan and protocols for the trial. Moreover, the FDA requires us to comply with GCPs for conducting, recording and reporting the results of clinical trials to assure that data and reported results are credible and accurate and that the rights, integrity and confidentiality of trial participants are protected. We also are required to register ongoing clinical trials and post the results of completed clinical trials on a government‑sponsored database within specified timeframes. Failure to do so can result in fines, adverse publicity and civil and criminal sanctions.

We also rely upon other third parties to store, package and distribute drug supplies for our clinical trials. Any performance failure on the part of our distributors could delay clinical development or marketing approval of our product candidates or commercialization of our products, producing additional losses and depriving us of potential product revenue.

We contract with third parties for the manufacture of our product candidates for clinical trials and expect to continue to do so in connection with the potential commercialization of either product candidate and for clinical trials and commercialization of any other product candidates that we develop or may develop. This reliance on third parties increases the risk that we will not have sufficient quantities of our product candidates or products or such quantities at an acceptable cost, which could delay, prevent or impair our development or commercialization efforts.

We do not currently own or operate manufacturing facilities for the production of clinical or commercial quantities of Zimura or Fovista and have limited personnel with manufacturing experience. We currently rely upon and expect to continue to rely upon third‑party contract manufacturers to manufacture preclinical and clinical supplies of product candidates we are developing or may develop and commercial supplies of products if and when approved for marketing by applicable regulatory authorities. Our current and anticipated future dependence upon others for the manufacture of the product candidates that we are developing or may develop may adversely affect our future profit margins and our ability to commercialize any products that receive marketing approval on a timely and competitive basis. In addition, any performance failure on the part of our existing or future manufacturers could delay clinical development or marketing approval.

We currently rely exclusively upon a single third-party manufacturer to provide supplies of both Zimura API and Fovista API and a different single third-party manufacturer to provide fill/finish services for Zimura and Fovista. Although we have agreements in place with Agilent for the supply of Fovista API and with Althea for clinical and commercial fill/finish services, we do not currently have any contractual commitments for the supply of Zimura API. We also do not currently have arrangements in place for redundant supply or a second source for API for Zimura or Fovista or for a redundant supply or a second source for fill/finish services. We purchase the proprietary polyethylene glycol, or PEG, reagent used to modify the chemically synthesized aptamer in Zimura on a purchase order basis from a single third-party supplier. We do not currently have any contractual commitments for supply of the PEG reagent we use for Zimura. The prices for manufacturing activities that are not yet contractually committed may vary substantially over time and adversely affect our financial results. Furthermore, we and our contract manufacturers currently rely upon sole-source suppliers of certain raw materials and other specialized components of production used in the manufacture and fill/finish of each of Zimura and Fovista.

If any of our third‑party manufacturers fail to fulfill our purchase orders, or if any of these manufacturers should become unavailable to us for any reason, including as a result of capacity constraints, financial difficulties or insolvency, we believe that there are a limited number of potential replacement manufacturers, and we likely would incur added costs and delays in identifying or qualifying such replacements. We could also incur additional costs and delays in identifying or qualifying a replacement manufacturer for fill/finish services if our existing third‑party fill/finish provider should become unavailable for any reason. We may be unable to establish agreements with such replacement manufacturers or fill/finish providers or to do so on acceptable terms.

~~Reliance on third‑party manufacturers entails additional risks, including:~~

our product candidates may compete with other product candidates and products for access to a limited number of suitable manufacturing facilities that operate under current good manufacturing practices, or cGMP, regulations;

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~~reliance on the third party for regulatory compliance, quality assurance and quality control;~~

~~the possible breach of the manufacturing agreement by the third party;~~

~~the possible misappropriation of our proprietary information, including our trade secrets and know‑how; and~~

~~the possible termination or nonrenewal of the agreement by the third party at a time that is costly or inconvenient for us.~~

Third‑party manufacturers may not be able to comply with cGMP regulations or similar regulatory requirements outside the United States. Our failure, or the failure of our third‑party manufacturers, to comply with applicable regulations could result in sanctions being imposed on us, including clinical holds, fines, injunctions, civil penalties, delays, suspension or withdrawal of approvals, license revocation, seizures or recalls of product candidates or products, operating restrictions and criminal prosecutions, any of which could significantly and adversely affect supplies of our products and harm our business and results of operations.

We depend on licenses and sublicenses for development and commercialization rights to ~~our~~IC-100, IC-200 and Zimura. These license arrangements, as well as the Inception 4 Merger Agreement, impose diligence obligations on us. We may enter into similar arrangements with respect to future product candidates ~~and~~or technologies. Termination of ~~these rights~~licenses or the failure by us or our licensees, including our potential future commercialization or collaboration partners, to comply with obligations under these or other agreements ~~under which we obtain such rights or have obtained funding~~ could materially harm our business and prevent us from developing or commercializing our products and product candidates.

We are party to ~~various~~two different license agreements, ~~that~~each with UFRF and Penn, on which we depend on for rights to ~~Zimura~~IC-100 and ~~Fovista.~~IC-200. We are also party to a license agreement with Archemix on which we depend for rights to Zimura. These agreements ~~impose, and we expect to enter into additional licensing arrangements or other agreements with third parties that would~~generally impose diligence, development and commercialization timelines, milestone payment, royalty, insurance and other obligations on us. Generally, the diligence obligations contained in these agreements require us to use commercially reasonable efforts to develop, seek regulatory approval for and commercialize the applicable product candidate in the United States and certain territories outside of the United States, including the European Union, Japan and such other markets where it would be commercially reasonable to do so. Under ~~our~~the license agreements ~~with Archemix~~for our product candidates, we would not be able to avoid our payment obligations even if we believed a licensed patent right was invalid or unenforceable because the license agreements provide that our licenses to all licensed patent rights would terminate if we challenge the validity or enforceability of any licensed patent right.

We The Inception 4 Merger Agreement, pursuant to which we acquired our HtrA1 inhibitor program, also ~~have~~imposes specified diligence and ~~development~~milestone payment obligations ~~under our license~~on us. We may enter into acquisition or licensing agreements with Archemix and our divestiture agreement with OSI Pharmaceuticals. Generally, these diligence obligations require us to use commercially reasonable efforts to develop, seek regulatory approval for and commercialize our products in the ~~United States, the European Union and, in some cases, certain other specified countries.~~ future that would impose similar obligations on us.

If we fail to comply with our obligations under current or future acquisition ~~license~~ and ~~funding~~licensing agreements, or otherwise breach an acquisition ~~license~~ or ~~funding~~licensing agreement as a result of our own actions or inaction or the actions or inactions of our commercialization or collaboration partners, our counterparties may have the right to terminate these agreements, in which event we might not have the rights or the financial resources to develop, manufacture or market any product that is covered by these agreements. Our counterparties also may have the right to convert an exclusive license to ~~non‑exclusive~~non-exclusive in the territory in which we fail to satisfy our diligence obligations, which could materially adversely affect the value of the product candidate being developed under any such agreement. Termination of these agreements or reduction or elimination of our rights under these agreements may result in our having to negotiate new or restated agreements with less favorable terms, seek alternative sources of financing or cause us to lose our rights under these agreements, including our rights to IC-100, IC-200, Zimura ~~Fovista~~ and other important intellectual property or technology. Any of the foregoing could prevent us from commercializing ~~Zimura, Fovista or other~~our product candidates, ~~we may develop,~~ which could have a material adverse effect on our operating results and overall financial condition. In the case of our limited diligence obligation under the Inception 4 Merger Agreement, a potential breach of our obligation to use

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commercially reasonable efforts to develop an HtrA1 inhibitor could lead to a lawsuit with the former equityholders of Inception 4 and result in potential liability to us of up to $5 million.

In addition to the above risks, certain of our intellectual property rights are sublicenses under intellectual property owned by third parties, in some cases through multiple tiers. The actions of our licensors may therefore affect our rights to use our sublicensed intellectual property, even if we are in compliance with all of the obligations under our license agreements. For example, the licenses from Archemix include sublicenses to us of rights to specified technology, which we refer to as the SELEX technology, licensed by University License Equity Holdings, Inc. to Gilead Sciences, Inc., or Gilead, and sublicensed by Gilead to Archemix, as well as other technology owned by Gilead and licensed to Archemix. Should our licensors or any of their upstream licensors fail to comply with their obligations under the agreements pursuant to which they obtain the rights that are sublicensed to us, or should such agreements be terminated or amended, our ability to develop and commercialize ~~Zimura, Fovista and other~~the relevant product candidates may be materially harmed. While the applicable agreements may contain contractual provisions that would in many instances protect our rights as a sublicensee in these circumstances, these provisions may not be enforceable and may not protect our rights in all instances. Further, we do not have the right to control the prosecution, maintenance and enforcement of all of our licensed and sublicensed intellectual property, and even when we do have such rights, we may require the cooperation of our licensors and their upstream licensors, which may not be forthcoming. Our

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business could be materially adversely affected if we are unable to prosecute, maintain and enforce our licensed and sublicensed intellectual property effectively.

Moreover, the license agreements for IC-100 and IC-200 reserve for the licensing academic institutions the right to continue to practice for research purposes, the inventions covered by the intellectual property rights that we have in-licensed. These licensing institutions or their collaborators may generate scientific, preclinical or clinical data with respect to our product candidates, separate from our research and development efforts, that is inconsistent with other data for such product candidates, including additional preclinical and clinical data that we develop. Investigators at these institutions may publish, present, or otherwise publicly disclose this data, which may have an adverse impact on the prospects of the development of our product candidates and may harm our business. In addition, these institutions may use these data to support new patent applications which could result in the issuance of patents that may limit our freedom to operate without our obtaining additional licenses to these newly developed inventions.

Risks Related to Our Intellectual Property

If we are unable to obtain and maintain or do not maintain patent protection for our technology and products during the period of their commercialization, or if the scope of the patent protection is not sufficiently broad, our competitors could develop and commercialize technology and products similar or identical to ours, and our ability to successfully commercialize our technology and products may be adversely affected.

We currently rely and expect to continue to rely on patent rights to protect our competitive position. Once our patents expire, we may not be able to exclude competitors from commercializing products similar or identical to ours. The U.S. patent rights covering Zimura as a composition of matter are expected to expire in 2025. The U.S. patent rights covering methods of treating certain complement protein mediated disorders with Zimura are expected to expire in 2026. The European patent rights covering the composition of matter of Zimura and methods of treating certain complement protein mediated disorders with Zimura are expected to expire in 2025. If data from ongoing clinical trials are positive, we expect the clinical development of Zimura to continue for at least the next several years. If so, the patents covering Zimura may expire before the date by which we or a potential commercial partner would be able to commercialize Zimura in the United States or Europe if we seek and obtain marketing approval. Even if we are able to obtain marketing approval for and commercially launch Zimura prior to the expiration of these patents, the remaining term of those patents may be shorter than we anticipate. Although the patent rights under existing patent applications for IC-100 and our HtrA1 inhibitors are not expected to expire until 2037 or 2039, we face the same risk with those product candidates and any future product candidates that we may develop.

Our product candidate IC-200 is not currently covered by a patent or pending patent application. In developing and advancing this product candidate, we may seek to rely on the prospect of generating new intellectual property during development of the product candidate or the potential for non-patent market exclusivity, including regulatory exclusivity as a result of the Orphan Drug Act. If we, together with Penn and UFRF, are unable to generate data to support a patent or patent application to cover this product candidate or if we are unable to obtain non-patent market exclusivity, we may not be able to exclude competitors from marketing an identical or substantially similar product.

For our sponsored research agreements with UMMS and Penn, we are generally relying on our university collaborators to generate research and data to support new patent applications. The results of any sponsored research are uncertain and the interests of the universities and university researchers are not necessarily aligned with our interests as a commercial entity. The research may generate limited patentable results or data, or none at all. Furthermore, the universities generally control the filing, prosecution and maintenance of any patents or patent applications resulting from the sponsored

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research. Therefore, we may not be able to obtain any patent or other exclusivity protections as a result of our collaborative gene therapy sponsored research programs, which could materially diminish or eliminate the value of these programs.

Certain of our licensed patent rights for Zimura are method-of-treatment patents. Method-of-treatment patents are more difficult to enforce than composition-of-matter patents because of the risk of off-label sale or use of a drug for the patented method. The FDA does not prohibit physicians from prescribing an approved product for uses that are not described in the product’s labeling. Although use of a product directed by off-label prescriptions may infringe our method-of-treatment patents, the practice is common across medical specialties, particularly in the United States, and such infringement is difficult to detect, prevent or prosecute. Off-label sales of other products having the same drug substance as Zimura or any other product candidates we may develop would limit our ability to generate revenue from the sale of Zimura or such other product candidates, if approved for commercial sale. In addition, European patent law generally makes the issuance and enforcement of patents that cover methods of treatment of the human body difficult. Further, once the composition-of-matter patents relating to Zimura or any other product candidate in a particular jurisdiction, if any, expire, competitors will be able to make, offer and sell products containing the same drug substance as Zimura or such other product candidate in that jurisdiction so long as these competitors do not infringe any of our other patents covering Zimura’s composition of matter or method of use or manufacture, do not violate the terms of any marketing or data exclusivity that may be granted to us by regulatory authorities and they obtain any necessary marketing approvals from applicable regulatory authorities. In such circumstances, we also may not be able to detect, prevent or prosecute off-label use of such competitors’ products containing the same drug substance as Zimura, even if such use infringes any of our method-of-treatment patents.

Depending on potential delays in the regulatory review process for any of our product candidates, we may be able to obtain patent term extension for one of our patents in the United States under the Hatch-Waxman Act, which permits a patent extension term of up to five years as partial compensation for patent term effectively lost during product development and the FDA regulatory review process occurring after the issuance of a patent, but we can provide no assurances that such an extension term will be obtained. Similar to the patent term extension available in the United States, the regulatory framework in the European Union and certain other foreign jurisdictions provides the opportunity to extend the term of a patent that covers an approved drug in certain circumstances. Notwithstanding the availability of patent term extension provisions, we may not be granted patent term extensions because of, for example, failing to apply within applicable deadlines, failing to apply prior to expiration of relevant patents or otherwise failing to satisfy applicable requirements, such as using diligent efforts to develop a drug candidate. Moreover, the applicable time period or the scope of patent protection afforded could be less than we request. If we are unable to obtain patent term extension or the term or scope of any such extension is less than we request, any period during which we have the right to exclusively market our product would be shorter than we would otherwise expect, and our competitors may commercialize competing products following our patent expiration, and our revenue could be reduced, possibly materially.

The Hatch-Waxman Act also permits the manufacture, use, offer for sale, sale or importation of a patented invention other than a new animal drug or veterinary biological product, if the manufacture, use, offer for sale, sale or importation is solely for uses that are reasonably related to development of information that could be submitted to the FDA. For this reason, our competitors might be able under certain circumstances to perform activities within the scope of the U.S. patents that we own or under which we are licensed without infringing such patents. This might enable our competitors to develop during the lifetime of these patents drugs that compete with our product candidates.

Our issued patents may not be sufficient to provide us with a competitive advantage. For example, competitors may be able to circumvent our owned or licensed patents by developing similar or alternative technologies or products in a non-infringing manner. Even if our owned or licensed patent applications issue as patents, they may not issue with a scope broad enough to provide us with any meaningful protection, prevent competitors from competing with us or otherwise provide us with any competitive advantage. We could also fail to take the required actions and pay the necessary governmental fees to maintain our patents.

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technology and products. The launch of a generic version of one of our products in particular would be likely to result in an immediate and substantial reduction in the demand for our product, which could have a material adverse effect on our business. 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 such candidates are commercialized. As a result, our patent portfolio may not provide us with sufficient rights to exclude others from commercializing products similar or identical to ours.

The patent prosecution process is expensive and ~~time~~‑~~consuming,~~time-consuming, is highly uncertain and involves complex legal and factual questions. Patent reform legislation could increase the uncertainties and costs surrounding the prosecution of our patent applications and the enforcement or defense of our issued patents.

Our success depends in large part on our ability to obtain and maintain patent protection in the United States and other countries with respect to our proprietary technology and products. We seek to protect our proprietary position by filing in the United States and in certain foreign jurisdictions patent applications related to our novel technologies and product candidates that are important to our business.

The patent prosecution process is expensive and ~~time‑consuming,~~time-consuming, and we may not be able to file and prosecute all necessary or desirable patent applications at a reasonable cost or in a timely manner. It is also possible that we will fail to identify patentable aspects of our research and development output before it is too late to obtain patent protection. In addition, we may not pursue or obtain patent protection in all major markets. Moreover, in some circumstances, we do not have the right to control the preparation, filing or prosecution of patent applications, or to maintain the patents, covering technology that we license from third parties or covering technology that a collaboration or commercialization partner may develop, the eventual commercialization of which could potentially entitle us to royalty payments. In some circumstances, our licensors may have the right to enforce the licensed patents without our involvement or consent, or to decide not to enforce or to allow us to enforce the licensed patents. Therefore, these patents and applications may not be prosecuted and enforced in a manner consistent with the best interests of our business. If any such licensors fail to maintain such patents, or lose rights to those patents, the rights that we have licensed may be reduced or eliminated and our ability to develop and commercialize any of our products that are the subject of such licensed rights could be adversely affected.

The patent position of biotechnology and pharmaceutical companies generally is highly uncertain, involves complex legal and factual questions and has in recent years been the subject of much litigation. In addition, the laws of foreign jurisdictions may not protect our rights to the same extent as the laws of the United States. For example, European patent law restricts the patentability of methods of treatment of the human body more than United States law does. Publications of discoveries in the scientific literature often lag behind the actual discoveries, and patent applications in the United States and other jurisdictions are typically not published until 18 months after filing, or in some cases not at all. Therefore, we cannot be certain that we or our licensors were the first to make the inventions claimed in our owned or licensed patents or pending patent applications, or that we or our licensors were the first to file for patent protection of such inventions. Moreover, the U.S. Patent and Trademark Office, or USPTO, might require that the term of a patent issuing from a pending patent application be disclaimed and limited to the term of another patent that is commonly owned or names a common inventor. As a result, the issuance, scope, validity, term, enforceability and commercial value of our patent rights are highly uncertain.

Our pending and future patent applications, and any collaboration or commercialization partner’s pending and future patent applications, may not result in patents being issued which protect our technology or products, in whole or in part, or which effectively prevent others from commercializing competitive technologies and products. In particular, during prosecution of any patent application, the issuance of any patents based on the application may depend upon our or their ability to generate additional preclinical or clinical data that support the patentability of our proposed claims. We or any collaboration or commercialization partner may not be able to generate sufficient additional data on a timely basis, or at all. Moreover, changes in either the patent laws or interpretation of the patent laws in the United States or other countries may diminish the value of our or a collaboration or commercialization partner’s patents or narrow the scope of our or their patent protection.

Patent reform legislation could increase the uncertainties and costs surrounding the prosecution of our patent applications and the enforcement or defense of our issued patents. ~~On September 16, 2011, the Leahy‑Smith~~The Leahy-Smith America Invents Act, or the ~~Leahy‑Smith~~Leahy-Smith Act, was signed into law. The Leahy‑Smith Act includes a number of significant changes to U.S. patent law. These include provisions that affect the way patent applications are prosecuted, redefine prior art, may affect patent litigation and switch the U.S. patent system from a “first‑to‑invent” system to a “first‑to‑file” system. Under a first‑to‑file system, assuming the other requirements for patentability are met, the first inventor to file a patent application generally will be entitled to the patent on an invention regardless of whether another inventor had made the invention earlier. The USPTO recently developed new regulations and procedures to govern administration of the Leahy‑Smith Act,law in September 2011, and many of the substantive changes tobecame effective in March 2013. The Leahy-Smith Act revised United States patent law ~~associated with~~in part by changing the ~~Leahy‑Smith Act,~~standard for patent approval from a “first to invent” standard to a “first to file” standard and developing a post-grant review system. This legislation changed United States patent law in ~~particular,~~a way that may weaken our ability to obtain patent protection in the ~~first��to‑~~United States for those applications filed after March 2013. For example, if we are the first to invent a new product or its use, but another party is the first to file ~~provisions, only became effective~~a patent application on ~~March 16, 2013. Accordingly, it is not clear what, if any, impact~~this invention, under the ~~Leahy‑Smith Act will have~~new law the other party may be entitled to the patent rights on the invention.

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operation of our business. However, the Leahy‑Smith Act and its implementation could increase the uncertainties and costs surrounding the prosecution of our patent applications and the enforcement or defense of our issued patents, all of which could have a material adverse effect on our business and financial condition.

Moreover, we may be subject to a ~~third‑party~~third-party preissuance submission of prior art to the USPTO, or become involved in opposition, derivation, reexamination, inter partes review, ~~post‑grant~~post-grant review, interference proceedings or other patent office proceedings or litigation, in the United States or elsewhere, challenging our patent rights or the patent rights of others. The Leahy-Smith Act expanded the ability of third parties to challenge the patents held by patentees through administrative reviews at the USPTO, which may facilitate others to challenge our patents. Based on available information, we believe that inter partes review proceedings, brought by financial investors who may be selling short the stock of the patent holder, are becoming more prevalent. An adverse determination in any such submission, proceeding or litigation could reduce the scope of, or invalidate, our patent rights; allow third parties to commercialize our technology or products and compete directly with us, without payment to us; or result in our inability to manufacture or commercialize products without infringing ~~third‑party~~third-party patent rights. 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.

The U.S. patent rights covering Zimura as a composition of matter are expected to expire in 2025. The U.S. patent rights covering methods of treating certain complement protein mediated disorders with Zimura are expected to expire in 2026. Such expiration dates may be prior to the date by which we would be able to commercialize Zimura in the United States if we seek and obtain marketing approval. As a result, if we obtain marketing approval for Zimura, we may not be able to exclude competitors from commercializing products similar or identical to ours if such competitors do not use or promote our claimed methods of treatment or do use or promote our methods of treatment after our patents expire. Depending on potential delays in the regulatory review process for Zimura, we may be able to obtain patent term restoration for one of these patents in the United States under the Hatch-Waxman Act, which permits a patent restoration term of up to five years as partial compensation for patent term effectively lost during product development and the FDA regulatory review process occurring after the issuance of a patent, but we can provide no assurances that such a restoration term will be obtained.

The European patent rights covering the composition of matter of Zimura and methods of treating certain complement protein mediated disorders with Zimura are expected to expire in 2025. Similar to the patent term restoration available in the United States, the regulatory framework in the European Union and certain other foreign jurisdictions provides the opportunity to extend the term of a patent that covers an approved drug in certain circumstances. Notwithstanding the availability of patent term extension or restoration provisions, we may not be granted patent term extensions because of, for example, failing to apply within applicable deadlines, failing to apply prior to expiration of relevant patents or otherwise failing to satisfy applicable requirements. Moreover, the applicable time period or the scope of patent protection afforded could be less than we request. If we are unable to obtain patent term extension or restoration or the term or scope of any such extension is less than we request, any period during which we have the right to exclusively market our product would be shorter than we would otherwise expect, and our competitors may obtain approval of competing products following our patent expiration, and our revenue could be reduced, possibly materially.

Method‑of‑treatment patents are more difficult to enforce than composition‑of‑matter patents because of the risk of off‑label sale or use of a drug for the patented method. The FDA does not prohibit physicians from prescribing an approved product for uses that are not described in the product’s labeling. Although use of a product directed by off‑label prescriptions may infringe our method‑of‑treatment patents, the practice is common across medical specialties, particularly in the United States, and such infringement is difficult to detect, prevent or prosecute. Off‑label sales of other products having the same API as Zimura or any other product candidates we may develop would limit our ability to generate revenue from the sale of Zimura or such other product candidates, if approved for commercial sale. In addition, European patent law generally makes the issuance and enforcement of patents that cover methods of treatment of the human body difficult. Further, once the composition‑of‑matter patents relating to Zimura or any other product candidate in a particular jurisdiction, if any, expire, competitors will be able to make, offer and sell products containing the same API as Zimura or such other product candidate in that jurisdiction so long as these competitors do not infringe any other of our patents covering Zimura’s composition of matter or method of use or manufacture, do not violate the terms of any marketing or data exclusivity that may be granted to us by regulatory authorities and obtain any necessary marketing approvals from applicable regulatory authorities. In such circumstances, we also may not be able to detect, prevent or prosecute off‑label use of such competitors’ products containing the same API as Zimura, even if such use infringes any of our method‑of‑treatment patents.

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The Hatch‑Waxman Act also permits the manufacture, use, offer for sale, sale or importation of a patented invention other than a new animal drug or veterinary biological product, if the manufacture, use, offer for sale, sale or importation is solely for uses that are reasonably related to development of information that could be submitted to the FDA. For this reason, our competitors might be able under certain circumstances to perform activities within the scope of the U.S. patents that we own or under which we are licensed without infringing such patents. This might enable our competitors to develop during the lifetime of these patents drugs that compete with our product candidates, if they are ultimately approved.

Our issued patents may not be sufficient to provide us with a competitive advantage. For example, competitors may be able to circumvent our owned or licensed patents by developing similar or alternative technologies or products in a non‑infringing manner. Even if our owned or licensed patent applications issue as patents, they may not issue with a scope broad enough to provide us with any meaningful protection, prevent competitors from competing with us or otherwise provide us with any competitive advantage. We could also fail to take the required actions and pay the necessary governmental fees to maintain our patents.

The issuance of a patent is not conclusive as to its inventorship, ownership, scope, term, validity or enforceability, and our owned and licensed patents may be challenged in the courts or patent offices in the United States and abroad. For example, if we receive marketing approval for our product candidates, other pharmaceutical companies may seek approval of generic versions of our products with the FDA or regulatory authorities in other jurisdictions. We may then be required to initiate proceedings against such companies in order to enforce our intellectual property rights. The risk of being involved in such proceedings is likely to increase if our products are commercially successful. In any such proceedings, the inventorship, ownership, scope, term, validity and enforceability of our patents may be challenged. These and other challenges may result in loss of exclusivity or freedom to operate or in patent claims being narrowed, invalidated or held unenforceable, in whole or in part, which could limit our ability to prevent others from using or commercializing similar or identical technology and products or from launching generic versions of our products, or could limit the duration of the patent protection of our technology and products. The launch of a generic version of one of our products in particular would be likely to result in an immediate and substantial reduction in the demand for our product, which could have a material adverse effect on our business. 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 such candidates are commercialized. As a result, our patent portfolio may not provide us with sufficient rights to exclude others from commercializing products similar or identical to ours.

We may become involved in lawsuits to protect or enforce our patents or other intellectual property, which could be expensive, time consuming and unsuccessful.

Competitors may infringe or otherwise violate our patents, trademarks, copyrights or other intellectual property. To counter infringement or other violations, we may be required to file claims, which can be expensive and time consuming. Any such claims could provoke these parties to assert counterclaims against us, including claims alleging that we infringe their patents or other intellectual property rights. In addition, in a patent infringement proceeding, a court may decide that one or more of the patents we assert is invalid or unenforceable, in whole or in part, construe the patent’s claims narrowly or refuse to prevent the other party from using the technology at issue on the grounds that our patents do not cover the technology. Similarly, if we assert trademark infringement claims, a court may determine that the marks we have asserted are invalid or unenforceable or that the party against whom we have asserted trademark infringement has superior rights to the marks in question. In such a case, we could ultimately be forced to cease use of such marks. In any intellectual property litigation, even if we are successful, any award of monetary damages or other remedy we receive may not be commercially valuable. 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.

Third parties may initiate legal proceedings or take other actions alleging that we are infringing or otherwise violating their intellectual property rights, the outcome of which would be uncertain and could have a material adverse effect on the success of our business.

Our commercial success depends upon our ability and the ability of ~~our~~any future collaboration and commercialization partners to develop, manufacture, market and sell our product candidates and products and use our proprietary technologies without infringing or otherwise violating the intellectual property and other proprietary rights of third parties. New patent applications in the field of biotechnology and pharmaceuticals, and gene therapies in particular, are being filed at a rapid pace.

There is considerable intellectual property litigation in the biotechnology and pharmaceutical industries. We or ~~our~~any future collaboration and commercialization partners may become party to, or threatened with, future adversarial proceedings or litigation regarding intellectual property rights with respect to our products and technology, including interference, derivation, ~~re‑examination, post‑grant~~re-examination, post-grant review, inter partes review, opposition, cancellation or similar proceedings before the USPTO or its foreign counterparts. The risks of being involved in such litigation and proceedings may ~~also~~ increase as our ~~or their~~ product candidates near commercialization.

Third parties may assert infringement claims against us or our collaboration or commercialization

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partners based on existing or future intellectual property rights. We or they may not be aware of all such intellectual property rights potentially relating to our product candidates and their manufacture and uses. There is a lag between the filing of a patent application, which generally establishes the priority date of a patent claim, and the publication of such patent application. During the period between filing of a patent application and publication of the application, we would not otherwise have a means of discovering the existence or extent of the claimed inventions contained in a filed but unpublished patent application. Patent applications are often drafted broadly, and the scope of patent claims that may ultimately issue may not be known until several years after a patent application is filed and published. We may make development or pipeline decisions based on our belief that our product candidates can be distinguished from patent claims contained in published patent applications or issued patents, that patent claims contained in published patent applications are unlikely to issue as drafted, or that claims contained in issued patents are invalid. These positions regarding third-party intellectual property may not ultimately be successful in litigation. Thus, we do not know with certainty that our product candidates, or our intended commercialization thereof, does not and will not infringe or otherwise violate any third party’s intellectual property.

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If we are or ~~one~~any of our future collaboration or commercialization partners is found to infringe or otherwise violate a third party’s intellectual property rights, we or they could be required to obtain a license from such third party to continue developing and marketing our product candidates or ~~their~~ products ~~and technology~~ or to continue using a trademark. However, we or our future collaboration and commercialization partners may not be able to obtain any required license on commercially reasonable terms or at all. Even if we or they were able to obtain a license, it could be ~~non‑exclusive,~~non-exclusive, thereby giving our competitors access to the same technologies licensed to us or our collaboration and commercialization partners and could require us or them to make substantial licensing and royalty payments. We or our future collaboration and commercialization partners could be forced, including by court order, to cease commercializing the infringing technology or product. In addition, we could be found liable for monetary damages, including treble damages and attorneys’ fees, if we are found to have willfully infringed a patent or other intellectual property right. A finding of infringement could prevent us or our future collaboration and commercialization partners from commercializing our ~~or their~~ product candidates or force us or them to cease some of our business operations, which could materially harm our business. Claims that we or our future collaboration and commercialization partners have misappropriated the confidential information or trade secrets of third parties could expose us or them to similar liabilities and have a similar negative impact on our business.

We may be subject to claims by third parties asserting that we or our employees have misappropriated their intellectual property, or claiming ownership of what we regard as our own intellectual property.

Many of our employees and contractors were previously employed at universities or other biotechnology or pharmaceutical companies, including our competitors or potential competitors. Although we try to ensure that our employees and contractors do not use the proprietary information or ~~know‑how~~know-how of others in their work for us, we may be subject to claims that we or these employees or contractors have used or disclosed intellectual property, including trade secrets or other proprietary information, of any such employee’s or contractor’s former employer. Litigation may be necessary to defend against these claims.

In addition, while it is our policy to require our employees and contractors who may be involved in the conception or development of intellectual property to execute agreements assigning such intellectual property to us, we may be unsuccessful in executing such an agreement with each party who in fact conceives or develops intellectual property that we regard as our own. Moreover, because we acquired rights to ~~Zimura~~our product candidates from ~~Archemix,~~third parties, we must rely upon ~~Archemix's~~these third parties and ~~its~~their successors' practices, and those of ~~its~~their predecessors, with regard to the assignment of intellectual property ~~therein.~~therein, including the intellectual property rights protecting the HtrA1 inhibitors we acquired in the Inception 4 acquisition transaction. Our and their assignment agreements may not be ~~self‑executing~~self-executing or may be breached, and we may be forced to bring claims against third parties, or defend claims they may bring against us, to determine the ownership of what we regard as our intellectual property.

If we fail in prosecuting or defending any such claims, in addition to paying monetary damages, we may lose valuable intellectual property rights or personnel.

Intellectual property litigation could cause us to spend substantial resources and could distract our personnel from their normal responsibilities.

Even if resolved in our favor, litigation or other legal proceedings relating to intellectual property claims may cause us to incur significant expenses and could distract our technical and management personnel from their normal responsibilities. In addition, there could be public announcements of the results of hearings, motions or other interim proceedings or developments, and if securities analysts or investors perceive these results to be negative, it could have a substantial adverse effect on the price of our common stock. Such litigation or proceedings could substantially increase our operating losses and reduce the resources available for development activities or any future sales, marketing or distribution activities. We may not have sufficient financial or other resources to conduct such litigation or proceedings adequately. Some of our competitors may be able to sustain the costs of such litigation or proceedings more effectively than we can because of their greater financial resources. Uncertainties resulting from the initiation and continuation of patent litigation or other proceedings could have a material adverse effect on our ability to compete in the marketplace.

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Obtaining and maintaining our patent protection depends on compliance with various procedural, documentary, fee payment and other requirements imposed by governmental patent offices, and our patent protection could be reduced or eliminated for ~~non~~‑~~compliance~~non-compliance with these requirements.

Periodic maintenance fees on any issued patent are due to be paid to the USPTO and patent offices in foreign countries in several stages over the lifetime of the patent. The USPTO and patent offices in foreign countries require compliance with a number of procedural, documentary, fee payment and other requirements during the patent application process. While an

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inadvertent lapse can in many cases be cured by payment of a late fee or by other means in accordance with the applicable rules, there are situations in which ~~non‑compliance~~non-compliance can result in abandonment or lapse of the patent or patent application, resulting in partial or complete loss of a patent or patent rights in the relevant jurisdiction. ~~Non‑compliance~~Non-compliance events that could result in abandonment or lapse of a patent or patent application include, but are not limited to, failure to respond to official actions within prescribed time limits, ~~non‑payment~~non-payment of fees and failure to properly legalize and submit formal documents. In such an event, our competitors might be able to enter the market sooner than we expect, which would have a material adverse effect on our business.

If we are unable to protect the confidentiality of our trade secrets, our business and competitive position would be harmed.

In addition to seeking patents for some of our technology and products, we also rely upon trade secrets, including unpatented ~~know‑how,~~know-how, technology and other proprietary information, to maintain our competitive position. We seek to protect these trade secrets, in part, by entering into ~~non‑disclosure~~non-disclosure and confidentiality agreements with parties who have access to them, such as our ~~employees, corporate collaborators,~~ outside scientific collaborators, contract manufacturers, ~~consultants,~~ advisors and other third parties. We also enter into confidentiality and invention or patent assignment agreements with our employees and consultants. We cannot guarantee that we have executed such agreements with each party that may have or have had access to our trade secrets. Moreover, because we acquired ~~certain rights to Zimura from Archemix,~~our HtrA1 inhibitor program through the acquisition of Inception 4, we ~~must rely~~are relying upon ~~Archemix's~~Inception 4's, and its ~~successors'~~prior owner's, practices ~~and those of its predecessors,~~ with regard to the protection of ~~Zimura‑related~~ trade secrets ~~before we acquired it.~~and intellectual property rights for the period prior to our acquisition of Inception 4. Any party with whom we or they have executed a ~~non‑disclosure~~non-disclosure and confidentiality agreement may breach that agreement and disclose our proprietary information, including our trade secrets, and we may not be able to obtain adequate remedies for such breaches. Our proprietary information may also be obtained by third parties by other means, such as breaches of our physical or computer security systems.

Detecting the disclosure or misappropriation of a trade secret and enforcing a claim that a party illegally disclosed or misappropriated a trade secret is difficult, expensive and ~~time‑consuming,~~time-consuming, and the outcome is unpredictable. In addition, some courts inside and outside the United States are less willing or unwilling to protect trade secrets. If any of our trade secrets were to be lawfully obtained or independently developed by a competitor, we would have no right to prevent them, or those to whom they communicate it, from using that technology or information to compete with ~~us. If any of our trade secrets were to be disclosed to or independently developed by a competitor,~~us and our competitive position would be harmed.

Risks Related to Information Technology

We rely significantly upon information technology systems and any failure, inadequacy, interruption or security lapse of these systems could harm our ability to operate our business effectively.

In the ordinary course of our business, we and our third-party contractors maintain personal and other sensitive data on our and their respective networks, including our intellectual property and proprietary or confidential information relating to our business and that of our clinical trial participants, business partners and employees. In particular, we rely on contract research organizations and other third parties to store and manage data generated from our preclinical research and development activities and information from our clinical trials. The secure maintenance of this sensitive information is critical to our business and reputation.

We have implemented a number of measures to protect our information technology systems. These measures include, among others, creation of a cyber-security governance team and standard operating procedures for responding to any cyber-security breaches, mandatory cyber-security training for our employees and consultants with access to our information technology systems and engagement of a third-party vendor to assess our informational technology systems and potential vulnerabilities.

Despite the implementation of security measures, our internal computer systems and those of our third-party contractors are vulnerable to compromise, damage, loss or exfiltration from cyber-attacks, computer viruses, unauthorized access, natural disasters, terrorism, war and telecommunication and electrical failures. In particular, companies and other entities and individuals have been increasingly subject to a wide variety of security incidents, cyber-attacks, phishing scams and other attempts to gain unauthorized access to systems and information, including through social engineering. The number and complexity of these threats continue to increase over time. These threats can come from a variety of sources, ranging in sophistication from individual hackers to state-sponsored attacks. Cyber threats may be broadly targeted, or they may be custom-crafted against our information systems or those of our third-party contractors.

For information stored with our third-party contractors, we rely upon, and the integrity and confidentiality of such information is dependent upon, the risk mitigation efforts such third-party contractors have in place. In the recent past, cyber-

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attacks have become more prevalent and much harder to detect and defend against. Our and our third-party contractors’ respective network and storage applications may be subject to unauthorized access by hackers or breached due to operator error, malfeasance or other system disruptions. We might not anticipate or immediately detect such incidents and the damage caused by such incidents. System failures, data breaches and any unauthorized access or disclosure of our information or intellectual property could compromise our intellectual property and expose sensitive business information. System failures or accidents or security breaches could cause interruptions in our operations, and could result in a material disruption of our research and development activities and business operations, in addition to possibly requiring substantial expenditures of resources to remedy. Moreover, if a breach of our security or that of our vendors occurs, the market perception of the effectiveness of our security measures could be harmed and our reputation and credibility could be damaged.

A data security breach could also lead to public or unauthorized exposure of personal information of our clinical trial patients, our employees or others. Cyber-attacks and the measures we implement to prevent, detect, and respond to them could cause us to incur significant remediation costs, result in product development delays, disrupt key business operations, expose us to contractual damages and/or regulatory liability, require us to make certain breach notifications, divert the attention of our management and key information technology resources, harm our reputation and deter patients, clinical investigators or other business partners from participating in our clinical trials or otherwise working with us. Any loss of preclinical data or clinical trial data could result in delays in our regulatory approval efforts and significantly increase our costs to recover or reproduce the data. To the extent that any disruption or security breach were to result in a loss of, or damage to, our data or applications, or inappropriate public disclosure of confidential or proprietary information, we could incur liability and our product development and commercialization efforts could be delayed. In addition, we may not have adequate insurance coverage to provide compensation for any losses associated with such events.

Compliance with global privacy and data security requirements could result in additional costs and liabilities to us or inhibit our ability to collect and process data globally, and the failure to comply with such requirements could have a material adverse effect on our business, financial condition or results of operations.

The regulatory framework for the collection, use, safeguarding, sharing, transfer and other processing of information worldwide is rapidly evolving and is likely to remain uncertain for the foreseeable future. Globally, virtually every jurisdiction in which we operate has established its own data security and privacy frameworks with which we must comply. For example, the collection, use, disclosure, transfer, or other processing of personal data regarding individuals in the European Union, including personal health data, is subject to the EU General Data Protection Regulation, or GDPR, which became effective on May 25, 2018. The GDPR is wide-ranging in scope and imposes numerous requirements on companies that process personal data, including requirements relating to processing health and other sensitive data, obtaining consent of the individuals to whom the personal data relates, providing information to individuals regarding data processing activities, implementing safeguards to protect the security and confidentiality of personal data, providing notification of data breaches, and taking certain measures when engaging third-party data processors. The GDPR also imposes strict rules on the transfer of personal data to countries outside the European Union, including the United States, and permits data protection authorities to impose large penalties for violations of the GDPR, including potential fines of up to €20 million or 4% of annual global revenues, whichever is greater. The GDPR also confers a private right of action on data subjects and consumer associations to lodge complaints with supervisory authorities, seek judicial remedies, and obtain compensation for damages resulting from violations of the GDPR. Given the breadth and depth of changes in data protection obligations, preparing for and complying with the GDPR’s requirements has required and will continue to require significant time, resources and a review of our technologies, systems and practices, as well as those of any third-party collaborators, service providers, contractors or consultants that process or transfer personal data collected in the European Union. The GDPR and other changes in laws or regulations associated with the enhanced protection of certain types of sensitive data, such as healthcare data or other personal information from our clinical trials, could require us to change our business practices, and any non-compliance by us or our employees, consultants or contractors could lead to government enforcement actions, private litigation, significant fines and penalties, or reputational harm and could have a material adverse effect on our business, financial condition or results of operations.

Risks Related to Regulatory Approval and Marketing of our Product Candidates and Other Legal Compliance Matters

Even if we complete the necessary preclinical studies and clinical trials, the marketing approval process is expensive, ~~time~~‑~~consuming~~time-consuming and uncertain and may prevent us from obtaining approvals for the commercialization of some or all of our product candidates. If we are not able to obtain, or if there are delays in obtaining, required regulatory approvals, we will not be able to commercialize our product candidates, and our ability to generate revenue would be materially impaired.

Our product candidates and the activities associated with their development and commercialization, including their design, testing, manufacture, safety, efficacy, recordkeeping, labeling, storage, approval, advertising, promotion, sale and distribution ~~export~~ and import and export, are subject to comprehensive regulation by the FDA, ~~and by~~ the EMA and comparable regulatory agencies in other countries.

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In general, the FDA and similar regulatory authorities outside the United States require two adequate and ~~well controlled~~well-controlled clinical trials demonstrating safety and effectiveness for marketing approval for an ophthalmic pharmaceutical product. Failure to obtain marketing approval for a product candidate will prevent us from commercializing the product candidate. We have not received approval to market ~~Zimura, Fovista or~~ any ~~other~~of our product ~~candidate~~candidates from regulatory authorities in any jurisdiction. We have only limited experience in filing and supporting the applications necessary to gain marketing approvals and expect to rely upon ~~third‑party~~third-party CROs to assist us in this process. Securing marketing approval requires obtaining positive safety and efficacy data from required clinical trials, as well as the submission of extensive preclinical and clinical data and supporting information to regulatory authorities for each ~~therapeutic~~ indication to establish the product candidate’s safety and efficacy. Securing marketing approval also requires the submission of information about the product manufacturing ~~process~~processes to, and inspection of manufacturing facilities by, the relevant regulatory authorities. The FDA or other

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regulatory authorities may determine that a product candidate that we may develop is not effective, is only moderately effective or has undesirable or unintended side effects, toxicities or other characteristics that preclude our obtaining marketing approval or prevent or limit commercial use. In the case of Zimura for the treatment of wet AMD, the FDA or other regulatory authority may limit the approval of Zimura to use with only specified anti‑VEGF drugs that are approved for the treatment of wet AMD rather than with all anti‑VEGF drugs. Such limitation could limit sales of Zimura for the treatment of wet AMD.

The process of obtaining marketing approvals, both in the United States and abroad, is expensive, may take many years, if approval is obtained at all, and can vary substantially based upon a variety of factors, including the type, complexity and novelty of the product candidates involved. Changes in marketing approval policies during the development period, changes in or the enactment of additional statutes or regulations, or changes in regulatory review for each submitted product application, may cause delays in the approval or rejection of an application. Regulatory authorities have substantial discretion in the approval process and may refuse to accept any application or may decide that our data are insufficient for approval and require additional preclinical, clinical or other studies. In addition, varying interpretations of the data obtained from preclinical and clinical testing could delay, limit or prevent marketing approval of a product candidate. Any marketing approval we ultimately obtain may be limited or subject to restrictions or ~~post‑approval~~post-approval commitments that render the approved product not commercially viable.

Marketing approval of novel product candidates such as Zimura and ~~Fovista~~our gene therapy product candidates manufactured using novel manufacturing processes can be more expensive and take longer than for other, more ~~well‑known~~well-known or extensively studied pharmaceutical or biopharmaceutical products, due to regulatory agencies’ lack of experience with them. We believe that the FDA has only granted marketing approval for one aptamer product and one gene replacement product to date. This lack of experience may lengthen the regulatory review process, require us to conduct additional studies or clinical trials, increase our development costs, lead to changes in regulatory positions and interpretations, delay or prevent approval and commercialization of these product candidates or lead to significant ~~post‑approval~~post-approval limitations or restrictions.

Accordingly, if we or our collaborators experience delays in obtaining approval or if we fail to obtain approval of ~~Fovista, Zimura or any other~~our product ~~candidate that we develop,~~candidates, the commercial prospects for such product candidate may be harmed and our ability to generate revenues would be materially impaired.

Failure to obtain marketing approval in foreign jurisdictions would prevent our product candidates from being marketed in such jurisdictions. The approval requirements in foreign jurisdictions may differ significantly from those in the United States.

In order to market and sell our product candidates in the European Union and many other jurisdictions, we or our ~~third‑party~~third-party commercialization partners must obtain separate marketing approvals and comply with numerous and varying regulatory requirements. The approval procedure varies among countries and can involve additional preclinical or clinical testing. The time required to obtain approval may differ substantially from that required to obtain FDA approval. The regulatory approval process outside the United States generally includes all of the risks associated with obtaining FDA approval. In addition, in many countries outside the United States, it is required that the product be approved for reimbursement before the product can be approved for sale in that country. We or our ~~third‑party~~third-party commercialization partners may not obtain marketing and/or reimbursement approvals from regulatory authorities outside the United States on a timely basis, if at all. Approval by the FDA does not ensure approval by regulatory authorities in other countries or jurisdictions, and approval by one regulatory authority outside the United States does not ensure approval by regulatory authorities in other countries or jurisdictions or by the FDA. We and our third-party commercialization partners may not be able to file for marketing approvals and may not receive necessary approvals to commercialize our products in any market.

Additionally, onin June ~~23,~~ 2016 the electorate in the United Kingdom voted in favor of leaving the European Union, commonly referred to as Brexit. ~~On March 29, 2017,~~The process for withdrawal has been and remains uncertain and convoluted, with the ~~country formally notified~~United Kingdom currently scheduled to withdraw from the European Union ~~of its intention to withdraw pursuant to Article 50 of~~on October 31, 2019, and currently, no effective withdrawal agreement has been concluded between the ~~Lisbon Treaty.~~European Union and the United Kingdom. Since a significant proportion of the regulatory framework in the United Kingdom is derived from European Union directives and regulations, ~~the referendum~~

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Brexit could materially impact the regulatory regime with respect to the approval of our product candidates in the United Kingdom or the European Union. Any delay in obtaining, or an inability to obtain, any marketing approvals, as a result of Brexit or otherwise, would prevent us from commercializing our product candidates in the United Kingdom and/or the European Union and restrict our ability to generate revenue and achieve and sustain profitability. If any of these outcomes occur, we may be forced to restrict or delay efforts to seek regulatory approval in the United Kingdom and/or European Union for our product candidates, which could significantly and materially harm our business.

~~Table~~ It remains to be seen how, if at all, Brexit will actually occur and how, if at all, Brexit will impact regulatory requirements for the approval of ~~Contents~~

pharmaceutical product candidates and the sale of pharmaceutical products in the United Kingdom and the European Union.

We currently do not have orphan drug designations or orphan drug exclusivity for any ~~product.~~product candidate. If our competitors are able to obtain orphan drug exclusivity for products that constitute the same drug and treat the same indications as our product candidates, we may not be able to have ~~competing products~~our product candidates approved by the applicable regulatory authority for a significant period of time.

Regulatory authorities in some jurisdictions, including the United States and the European Union, may designate drugs for relatively small patient populations as orphan drugs. Under the Orphan Drug Act, the FDA may designate a product candidate as an orphan drug if it is intended to treat a rare disease or condition, which is generally defined as having a patient population of fewer than 200,000 individuals in the United States, or a patient population greater than 200,000 in the United States where there is no reasonable expectation that the cost of developing the drug will be recovered from sales in the United States. In the European Union, the EMA’s Committee for Orphan Medicinal Products grants orphan drug designation to promote the development of products that are intended for the diagnosis, prevention or treatment of a life-threatening or chronically debilitating condition affecting not more than 5 in 10,000 persons in the European Union. Additionally, orphan designation is granted for products intended for the diagnosis, prevention or treatment of a life-threatening, seriously debilitating or serious and chronic condition and when, without incentives, it is unlikely that sales of the drug in the European Union would be sufficient to justify the necessary investment in developing the drug or biologic product.

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

Generally, if a product candidate with an orphan drug designation receives the first marketing approval for the indication for which it has such designation, the product is entitled to a period of marketing exclusivity, which precludes the FDA or the European Commission during that marketing exclusivity period from approving another marketing application for a product that constitutes the same drug treating the same indication, ~~for that marketing exclusivity period,~~ except in limited circumstances. If another sponsor receives such approval before we do, ~~(regardless~~regardless of our orphan drug ~~designation),~~designation, we will be precluded from receiving marketing approval for our product ~~for~~candidate during the applicable exclusivity period. The applicable period is seven years in the United States and 10 years in the European Union. The exclusivity period in the United States can be extended by six months if the sponsor submits pediatric data that fairly respond to a written request from the FDA for such data. The exclusivity period in the European Union can be reduced to six years if a product no longer meets the criteria for orphan drug designation or if the product is sufficiently profitable so that market exclusivity is no longer justified. Orphan drug exclusivity may be revoked if any regulatory agency determines that the request for designation was materially defective or if the manufacturer is unable to assure sufficient quantity of the product to meet the needs of patients with the rare disease or condition.

Even if we obtain orphan drug exclusivity for a product candidate, that exclusivity may not effectively protect the product candidate from competition because different drugs can be approved for the same condition. In the United States, even after an orphan drug is approved, the FDA may subsequently approve another drug for the same condition if the FDA concludes that the ~~latter~~later drug is not the same drug or is clinically superior in that it is shown to be safer, more effective or makes a major contribution to patient care. In particular, the concept of what constitutes the "same drug" for purposes of orphan drug exclusivity is unclear in the context of gene therapies, and the FDA has issued draft guidance suggesting minor variations in the construct of a gene therapy that lead to improvements in safety or efficacy may result in the determination that a drug is a "different drug". In the European Union, marketing authorization may be granted to a similar medicinal product for the same orphan indication if:

the second applicant can establish in its application that its medicinal product, although similar to the orphan medicinal product already authorized, is safer, more effective or otherwise clinically superior;

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the holder of the marketing authorization for the original orphan medicinal product consents to a second orphan medicinal product application; or

the holder of the marketing authorization for the original orphan medicinal product cannot supply sufficient quantities of the orphan medicinal product.

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A fast track designation or grant of priority review status by the FDA may not actually lead to a faster development or regulatory review or approval process. The FDA may withdraw fast track designation if it believes that the designation is no longer supported by data from our clinical development program.

IfThe FDA may designate a ~~drug~~product for fast track review if it is intended, whether alone or in combination with one or more other products, for the treatment of a serious or ~~life‑threatening~~life-threatening disease or condition, and if the ~~drug~~product demonstrates the potential to address unmet medical needs for ~~this~~such a disease or ~~condition, the drug sponsor may apply for FDA~~condition. For fast track ~~designation. If~~products, sponsors may have greater interactions with the FDA and the FDA may initiate review of sections of a ~~drug offers major advances~~fast track product’s application before the application is complete. This rolling review may be available if the FDA determines, after preliminary evaluation of clinical data submitted by the sponsor, that a fast track product may be effective. The sponsor must also provide, and the FDA must approve, a schedule for the submission of the remaining information and the sponsor must pay applicable user fees. However, the FDA’s time period goal for reviewing a fast track application does not begin until the last section of the application is submitted. In addition, the fast track designation may be withdrawn by the FDA if the FDA believes that the designation is no longer supported by data emerging in ~~treatment,~~ the ~~drug sponsor may apply for FDA priority review status.~~ clinical trial process.

The FDA has broad discretion whether or not to grant fast track designation or priority review status, so even if we believe a particular product candidate is eligible for such designation or status the FDA could decide not to grant it. Even though a product has received fast track designation and may be eligible for priority review status, a sponsor may not ultimately experience a faster development process, review or approval compared to conventional FDA procedures.

A breakthrough therapy designation by the FDA for our product candidates may not lead to a faster development or regulatory review or approval process, and it does not increase the likelihood that our product candidates would receive marketing approval.

WeIn 2012, Congress enacted the Food and Drug Administration Safety and Innovation Act, or FDASIA. This law established a new regulatory scheme allowing for expedited review of products designated as “breakthrough therapies.” A product may ~~seek~~be designated as a breakthrough therapy ~~designation for some of our product candidates. A breakthrough therapy~~if it is ~~defined as a drug that is~~ intended, either alone or in combination with one or more other ~~drugs,~~products, to treat a serious or ~~life‑threatening~~life-threatening disease or condition and preliminary clinical evidence indicates that the ~~drug~~product may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development. ~~For drugs that have been designated as~~The FDA may take certain actions with respect to breakthrough therapies, ~~interactions and communications between the FDA and~~including holding meetings with the sponsor ofthroughout the ~~trial can help~~development process; providing timely advice to ~~identify~~ the ~~most~~product sponsor regarding development and approval; involving more senior staff in the review process; assigning a cross-disciplinary project lead for the review team; and taking other steps to design the clinical trials in an efficient path for clinical development while minimizing the number of patients placed in ineffective control regimens. Drugs designated as breakthrough therapies by the FDA are also eligible for accelerated approval.manner.

Designation as a breakthrough therapy is within the discretion of the FDA. Accordingly, even if we believe one of our product candidates meets the criteria for designation as a breakthrough therapy, the FDA may disagree and instead ~~determine~~decide not to make such designation. In any event, the receipt of a breakthrough therapy designation for a product candidate may not result in a faster development process, review or approval compared to drugs considered for approval under conventional FDA procedures and does not ~~assure~~ensure ultimate approval by the FDA. In addition, even if one or more of our product candidates qualify as breakthrough therapies, the FDA may later decide that the products no longer meet the conditions for qualification or ~~decide~~ that the time period for FDA review or approval will not be shortened.

Any product candidate for which we obtain marketing approval could be subject to ~~post~~‑~~marketing~~post-marketing restrictions or withdrawal from the market and we or our ~~third~~‑~~party~~third-party commercialization partners may be subject to penalties if we or our ~~third~~‑~~party~~third-party commercialization partners or our or their manufacturers fail to comply with regulatory requirements or if we or our ~~third~~‑~~party~~third-party commercialization partners or our or their manufacturers experience unanticipated problems with our products, when and if any of them are approved.

Any product candidate for which we or our commercialization partners obtain marketing approval, along with the manufacturing processes, ~~post‑approval~~post-approval clinical data, labeling, advertising and promotional activities for such product, will be subject to ~~continual~~the continued requirements of and review by the FDA and other regulatory authorities. These requirements include submissions of safety and other ~~post‑marketing~~post-marketing information and reports, registration and listing requirements, cGMP requirements relating to manufacturing, quality control and quality assurance, complaints and corresponding maintenance of

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records and documents, requirements regarding the distribution of samples to physicians and recordkeeping. Even if marketing approval of a product candidate is granted, the approval may be subject to limitations on the indicated uses for which the product may be marketed or may be subject to significant conditions of approval or contain requirements for costly ~~post‑marketing~~post-marketing testing and surveillance to monitor the safety or efficacy of the medicine, including the requirement to implement a risk evaluation and mitigation strategy.

The FDA and other agencies, including the Department of Justice, or the DOJ, closely regulate and monitor the ~~post‑approval~~post-approval marketing and promotion of products to ensure that they are marketed and distributed only for the approved indications and in accordance with the provisions of the approved labeling. The FDA and DOJ impose stringent restrictions on ~~manufacturers’~~manufacturers' communications regarding ~~off‑label~~off-label use and if we do not market our products for their approved indications, we may be subject to enforcement action for ~~off‑label~~off-label marketing. Violations of the ~~Federal Food, Drug, and Cosmetic Act~~FDCA and other statutes, including the False Claims Act, relating to the promotion and advertising of prescription drugs may lead to investigations and enforcement actions alleging violations of federal and state health care fraud and abuse laws, as well as state consumer protection laws.

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In addition, later discovery of previously unknown adverse events or other problems with our products, manufacturers or manufacturing processes, or failure to comply with regulatory requirements, may yield various results, including:

restrictions on such products, manufacturers or manufacturing processes;

restrictions on the labeling or marketing of a product;

restrictions on distribution or use of a product;

requirements to conduct ~~post‑marketing~~post-marketing studies or clinical trials;

warning letters or untitled letters;

~~withdrawal of the products from the market;~~

refusal to approve pending applications or supplements to approved applications that we submit;

recall of products;

damage to relationships with any potential collaborators;

unfavorable press coverage and damage to our reputation;

fines, restitution or disgorgement of profits or revenues;

suspension or withdrawal of marketing approvals;

refusal to permit the import or export of our products;

product seizure;

injunctions or the imposition of civil or criminal penalties; and

litigation involving patients using our products.

~~Non‑compliance~~Non-compliance with European Union requirements regarding safety monitoring or pharmacovigilance, and with requirements related to the development of products for the pediatric population, can also result in significant financial penalties. Similarly, failure to comply with the European Union’s requirements regarding the protection of personal information, such as the GDPR, can also lead to significant penalties and sanctions.

Our and our potential commercialization partners’ relationships with customers and ~~third~~‑~~party~~third-party payors will be subject to applicable ~~anti~~‑~~kickback,~~anti-kickback, fraud and abuse and other healthcare laws and regulations, which could expose us and our commercialization partners to criminal sanctions, civil penalties, contractual damages, reputational harm and diminished profits and future earnings.

Healthcare providers, physicians and ~~third‑party~~third-party payors play a primary role in the recommendation and prescription of any product candidates for which we obtain marketing approval. Our future arrangements with healthcare providers, physicians

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and third-party payors may expose us and our commercialization partners to broadly applicable fraud and abuse and other healthcare laws and regulations that may constrain the business or financial arrangements and relationships through which we and our commercialization partners market, sell and distribute any products for which we or they obtain marketing approval. Restrictions under applicable federal and state healthcare laws and regulations include the following:

the federal ~~Anti‑Kickback~~Anti-Kickback Statute prohibits, among other things, persons from knowingly and willfully soliciting, offering, receiving or providing remuneration, directly or indirectly, in cash or in kind, to induce or reward, or in return for, either the referral of an individual for, or the purchase, order or recommendation or arranging of, any good or service, for which payment may be made under a federal healthcare program such as Medicare and Medicaid;

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the federal False Claims Act imposes criminal and civil penalties, including through civil whistleblower or qui tam actions, against individuals or entities for, among other things, knowingly presenting, or causing to be presented, false or fraudulent claims for payment by a federal healthcare program or making a false statement or record material to payment of a false claim or avoiding, decreasing or concealing an obligation to pay money to the federal government, with potential liability including mandatory treble damages and significant ~~per‑claim~~per-claim penalties, currently set at ~~$5,500 to $11,000~~a minimum of $10,781 and a maximum of $20,563 per false claim;

the federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, imposes criminal and civil liability for executing a scheme to defraud any healthcare benefit program or making false statements relating to healthcare matters;

HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act and its implementing regulations, also imposes obligations, including mandatory contractual terms, with respect to safeguarding the privacy, security and transmission of individually identifiable health information;

the federal Physician Payments Sunshine Act requires ~~applicable~~certain manufacturers of drugs, medical devices and biological products covered ~~drugs~~by federal healthcare benefit programs to report payments and other transfers of value to physicians and teaching ~~hospitals, with data collection beginning in August 2013;~~hospitals; and

analogous state and foreign laws and regulations, such as state ~~anti‑kickback~~anti-kickback and false claims laws and transparency statutes, may apply to sales or marketing arrangements and claims involving healthcare items or services reimbursed by ~~non‑~~governmental and non-governmental third-party payors, including private insurers.

Some state laws require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government and may require drug manufacturers to report information related to payments and other transfers of value to physicians and other healthcare providers or marketing expenditures. State and foreign laws also govern the privacy and security of health information in some circumstances, many of which differ from each other in significant ways and often are not preempted by HIPAA, thus complicating compliance efforts.

If our operations are found to be in violation of any of the laws described above or any governmental regulations that apply to us, we may be subject to penalties, including civil and criminal penalties, damages, fines and the curtailment or restructuring of our operations. Any penalties, damages, fines, curtailment or restructuring of our operations could adversely affect our financial results. ~~We are developing~~As our product candidates advance in clinical development, we plan to develop and ~~implementing~~implement a corporate compliance program ~~designed~~ to ensure that we will market and sell any future products that we successfully develop ~~from our product candidates~~ in compliance with all applicable laws and regulations, but we cannot guarantee that ~~this~~any such program will protect us from governmental investigations or other actions or lawsuits stemming from a failure to be in compliance with such laws orand regulations. If any such actions are instituted against us and we are not successful in defending ourselves or asserting our rights, those actions could have a significant impact on our business, including the imposition of significant fines or other sanctions.

Efforts to ensure that our business arrangements with third parties will comply with applicable healthcare laws and regulations will involve substantial costs. It is possible that governmental authorities will conclude that our business practices may not comply with current or future statutes, regulations or case law involving applicable fraud and abuse or other healthcare laws and regulations. If our or our commercialization partners’ operations are found to be in violation of any of these laws or any other governmental regulations that may apply to us or them, we or they may be subject to significant civil, criminal and administrative penalties, including damages, fines, ~~imprisonment,~~ exclusion of products from government funded healthcare programs, such as Medicare and Medicaid, and the curtailment or restructuring of our or their operations. If any of the physicians or other healthcare providers or entities with whom we expect to do business is found to be not in compliance with applicable laws, they

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may be subject to criminal, civil or administrative sanctions, including exclusions from government funded healthcare programs.

~~The efforts of the Trump Administration to pursue regulatory reform~~Our operations may ~~limit the FDA’s ability to engage in oversight and implementation activities in~~be dependent on the normal ~~course,~~function on the FDA, the SEC and ~~that~~other government agencies. The inability of those agencies to obtain necessary funding and other effects from the political process could prevent those agencies from performing normal functions on which the operation of our business may rely, which could negatively impact our business.

The ability of the FDA to review and approve new product applications such as INDs, new drug applications and biologics license applications can be affected by a variety of factors, including government funding levels, ability to hire and retain key personnel and to accept the payment of user fees, and statutory, regulatory, and policy changes. Government funding of the FDA, the SEC and other government agencies on which our operations may rely is subject to the political process, which is inherently fluid and unpredictable. For example, over the last several years, the U.S. government has shut down several times and certain regulatory agencies, such as the FDA and the SEC, have had to furlough critical employees and stop critical activities. If a prolonged government shutdown occurs, it could significantly impact the ability of the FDA to timely review and process our regulatory submissions, which could have a material adverse effect on our business. Further, in our operations as a public company, future government shutdowns could impact our ability to access the public markets and obtain necessary capital in order to properly capitalize and continue our operations. In addition, the Trump Administration has taken several executive actions, including the issuance of a number of executive orders, that could affect federal agencies, including the FDA. Those executive actions, some of which are still being implemented, may impose significant burdens on, or otherwise materially delay, the FDA’s ability to engage in routine regulatory and oversight activities, such as implementing statutes through rulemaking, issuance of guidance, and review and approval of marketing applications. On January 30, 2017, President Trump issued an executive order, applicable to all executive agencies, including the FDA, which ~~requires that for each notice of proposed rulemaking or final regulation to be issued in fiscal year~~

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2017, the agency shall identify at least two existing regulations to be repealed, unless prohibited by law. These requirements are referred to as the “two-for-one” provisions. This executive order includes a budget neutrality provision that requires the total incremental cost of all new regulations in the 2017 fiscal year, including repealed regulations, to be no greater than zero, except in limited circumstances. For fiscal years 2018 and beyond, the executive order requires agencies to identify regulations to offset any incremental cost of a new regulation. In interim guidance issued by the Office of Information and Regulatory Affairs within the Office of Management and Budget on February 2, 2017, the administration indicates that the “two-for-one” provisions may apply not only to agency regulations, but also to significant agency guidance documents. It is difficult to predict how these requirements will be implemented, and the extent to which they willcould negatively impact the FDA’s ability to exercise its regulatory authority. If these executive actions impose constraints on the FDA’s ability to engage in oversight and implementation activities in the normal course, our ~~business may be negatively impacted.~~

business.

Current and future legislation and regulations may increase the difficulty and cost for us and any future collaborators to obtain marketing approval of and commercialize our product candidates and affect the prices we or they may ~~obtain.~~charge for such products, when and if approved.

In the United States and some foreign jurisdictions, there have been ~~and continue to be~~ a number of legislative and regulatory changes and proposed changes regarding the healthcare system that could, among other things, prevent or delay marketing approval of our product candidates, restrict or regulate ~~post‑approval~~post-approval activities and affect our ~~and~~ability, or the ability of any ~~commercialization partner’s ability~~collaborators, to ~~generate revenue from,~~profitably sell ~~profitably or commercialize~~ any ~~product candidates~~products for which we, or they, obtain marketing approval. We expect that current laws, as well as other healthcare reform measures that may be adopted in the future, may result in more rigorous coverage criteria and in additional downward pressure on the price that we, or ~~a commercialization partner~~any future collaborators, may ~~receive~~charge for any approved products.

In March 2010, President Barack H. Obama signed into law the Patient Protection and Affordable Care Act, as amended by the Health Care and Education Reconciliation Act, or collectively the ACA. Among the provisions of the ACA of potential importance to our business and our product candidates are the following:

an annual, ~~non‑deductible~~non-deductible fee on any entity that manufactures or imports specified branded prescription products and biologic agents;

an increase in the statutory minimum rebates a manufacturer must pay under the Medicaid Drug Rebate Program;

expansion of healthcare fraud and abuse laws, including the civil False Claims Act and the federal ~~Anti‑Kickback~~Anti-Kickback Statute, new government investigative powers and enhanced penalties for noncompliance;

a new Medicare Part D coverage gap discount program, in which manufacturers must agree to offer, originally 50% ~~point‑of‑sale~~and as of 2019, 70%, point-of-sale discounts off negotiated prices;

extension of manufacturers’ Medicaid rebate liability;

expansion of eligibility criteria for Medicaid programs;

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

new requirements to report certain financial arrangements with physicians and teaching hospitals;

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

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

In addition, other legislative changes have been proposed and adopted since the ACA was enacted. These changes include the Budget Control Act of 2011, which, among other things, led to aggregate reductions to Medicare payments to providers of up to 2% per fiscal year that started in 2013 and, due to subsequent legislative amendments to the statute, will stay in effect through 2025 unless additional congressional action is ~~taken. The~~taken, and the American Taxpayer Relief Act of 2012, which, among other things, reduced Medicare payments to several types of providers and increased the statute of limitations period for the government to recover overpayments to providers from three to five years. These new laws may result in additional reductions in Medicare and other healthcare funding and otherwise affect the prices we may obtain for any of our product candidates for

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which we may obtain regulatory approval or the frequency with which any such product candidate is prescribed or used. Further, there have been several recent U.S. congressional inquiries and proposed state and federal legislation designed to, among other things, bring more transparency to drug pricing, review the relationship between pricing and manufacturer patient programs, reduce the costs of drugs under Medicare and reform government program reimbursement methodologies for drug products.

We expect that these healthcare reforms, as well as other healthcare reform measures that may be adopted in the future, may result in additional reductions in Medicare and other healthcare funding, more rigorous coverage criteria, new payment methodologies and additional downward pressure on the price that we receive for any approved product and/or the level of reimbursement physicians receive for administering any approved product we might bring to market. Reductions in reimbursement levels may negatively impact the prices we receive or the frequency with which our products are prescribed or administered. Any reduction in reimbursement from Medicare or other government programs may result in a similar reduction in payments from private payors.

Since enactment of the ACA, there have been numerous legal challenges and congressional actions to repeal and replace provisions of the law. ~~In May~~For example, with enactment of the Tax Cuts and Jobs Act of 2017, Congress repealed the ~~U.S. House~~“individual mandate.” The repeal of ~~Representatives passed legislation known~~this provision, which required most Americans to carry a minimal level of health insurance, became effective in 2019. According to the Congressional Budget Office, the repeal of the individual mandate will cause 13 million fewer Americans to be insured in 2027 and premiums in insurance markets may rise. Further, the Bipartisan Budget Act of 2018, among other things, amended the ACA, effective January 1, 2019, to increase from 50 percent to 70 percent the point-of-sale discount that is owed by pharmaceutical manufacturers who participate in Medicare Part D and to close the coverage gap in most Medicare drug plans, commonly referred to as the ~~American Health Care Act~~“donut hole.” Congress may consider other legislation to amend or replace elements of ~~2017. Thereafter, the Senate Republicans introduced and then updated a bill to replace~~ the ACA ~~known as~~during the Better Care Reconciliation Act of 2017. The Senate Republicans also introduced legislation to repeal the ACA without companion legislation to replace it, and a “skinny” version of the Better Care Reconciliation Act of 2017. In addition, the Senate considered proposed healthcare reform legislation known as the Graham-Cassidy bill. None of these measures have been passed by the U.S. Senate.current congressional session.

The Trump Administration has also taken executive actions to undermine or delay implementation of the ~~ACA. In~~ACA, which has lead to numerous legal challenges to the ACA and the Trump Administration's actions. Since January 2017, President Trump has signed ~~an Executive Order directing~~at least two executive orders designed to delay the implementation of certain provisions of the ACA or otherwise circumvent some of the requirements for health insurance mandated by the ACA. One executive order directs federal agencies with authorities and responsibilities under the ACA to waive, defer, grant exemptions from, or delay the implementation of any provision of the ACA that would impose a fiscal or regulatory burden on states, individuals, healthcare providers, health insurers, or manufacturers of pharmaceuticals or medical devices. ~~In October 2017,~~A second executive order terminated the ~~President signed~~cost-sharing subsidies that reimburse insurers under the ACA, which has lead some states attorneys general and some insurers to sue the Trump Administration for such payments and a ~~second Executive Order allowing~~number of those lawsuits remain pending. Further, in June 2018, the U.S. Court of Appeals for the ~~use of association health plans~~Federal Circuit ruled that the federal government was not required to pay more than $12 billion in ACA risk corridor payments to third-party payors who argued the payments were owed to them. That lawsuit is currently pending possible review by the U.S. Supreme Court. In addition, in October 2018 CMS promulgated regulations that would give states greater flexibility in setting benchmarks for insurers in the individual and ~~short-term health insurance,~~small group marketplaces, which may ~~provide fewer~~have the effect of relaxing the essential health benefits ~~than~~required under the ACA for plans sold through the ACA exchanges. At the same time, the Administration announced that it will discontinue the payment of cost-sharing reduction, or CSR, payments to insurance companies until Congress approves the appropriation of funds for such ~~CSR payments. The loss of the CSR payments is expected to increase premiums on certain policies issued by qualified health plans under the ACA.~~marketplaces.

A bipartisan bill to appropriate funds for CSR payments was introduced in the Senate, but the future of that bill is uncertain. Further, each chamber of the Congress has put forth multiple bills designed to repeal or repeal and replace portions of the ACA. Although none of these measures has been enacted by Congress to date, Congress may consider other legislation to repeal and replace elements of the ACA. The Congress will likely consider other legislation to replace elements of the ACA, during the next congressional session. We will continue to evaluate the effect that the ACA, ~~and~~ its possible amendment or repeal and ~~replacement~~the actions of the Trump Administration in relation to the ACA could have on our business. It is possible that amendment or repeal initiatives, if enacted into law, could ultimately result in fewer individuals having health insurance coverage or in individuals having insurance coverage with less generous benefits. Accordingly, such reforms, if enacted, could have an adverse effect on anticipated revenue from product candidates that we may successfully develop and for which we may obtain marketing approval and may affect our overall financial condition and ability to develop or commercialize product candidates. While the timing and scope of any potential future legislation to amend or repeal ACA provisions is highly uncertain in many respects, including the possibility that any such amendment or repeal is brought about by a court ruling rather than legislative action, it is also possible that some of the ACA provisions that generally are not favorable for the research-based pharmaceutical industry could also be amended or repealed.

The costs of prescription pharmaceuticals in the United States has also been the subject of considerable discussion in the United States, and members of Congress and the Trump Administration have stated that they will address such costs through new legislative and administrative measures. In May 2018, the Trump Administration announced a plan that would include several initiatives designed to lower drug prices and additional similar proposals from HHS and CMS have followed. At the state level, individual states are increasingly passing legislation and implementing regulations designed to control pharmaceutical and biological product pricing. Additionally, third party payors, regional health care authorities and individual hospitals are increasingly using bidding procedures to determine what pharmaceutical products and which suppliers will be

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included in their prescription drug and other health care programs. We expect additional measures addressing pharmaceutical pricing to be proposed and may be adopted in the future, which could reduce the ultimate demand for our products, once approved, or put pressure on our product pricing.

The pricing of prescription pharmaceuticals is also subject to governmental control outside the United States. In these countries, pricing negotiations with governmental authorities can take considerable time after the receipt of marketing approval for a product. To obtain reimbursement or pricing approval in some countries, we may be required to conduct a clinical trial that compares the ~~cost‑~~cost effectiveness of our product candidates to other available therapies. If reimbursement of our products is unavailable or limited in scope or amount, or if pricing is set at unsatisfactory levels, our ability to generate revenues and become profitable could be impaired. In the European Union, similar political, economic and regulatory developments as those in the United States may affect our ability to profitably commercialize our products, if approved.

Finally, legislative and regulatory proposals have also been made to expand post-approval requirements and restrict sales and promotional activities for pharmaceutical products. We cannot be sure whether additional legislative changes will be enacted, or whether the FDA regulations, guidance or interpretations will be changed, or what the impact of such changes on the ~~marketing approvals~~commercialization of our product candidates, if any, may be. In addition, increased scrutiny by the U.S. Congress of the FDA’s approval process may significantly delay or prevent marketing approval, as well as subject us and any future collaborators to more stringent product labeling and post-marketing testing and other requirements.

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We are subject to U.S. and foreign ~~anti~~‑~~corruption~~anti-corruption and ~~anti~~‑~~money~~anti-money laundering laws with respect to our operations and ~~non~~‑~~compliance~~non-compliance with such laws can subject us to criminal and/or civil liability and harm our business.

We are subject to the U.S. Foreign Corrupt Practices Act of 1977, as amended, or the FCPA, the U.S. domestic bribery statute contained in 18 U.S.C. § 201, the U.S. International Travel Act of 1961, the USA PATRIOT Act, and possibly other state and national ~~anti‑bribery~~anti-bribery and ~~anti‑money~~anti-money laundering laws in countries in which we conduct activities. ~~Anti‑corruption~~Anti-corruption laws are interpreted broadly and prohibit companies and their employees, agents, ~~third‑party~~third-party intermediaries, joint venture partners and collaborators from authorizing, promising, offering, or providing, directly or indirectly, improper payments or benefits to recipients in the public or private sector. We may have direct or indirect interactions with officials and employees of government agencies or ~~government‑affiliated~~government-affiliated hospitals, universities, and other organizations. In addition, we may engage third party intermediaries to promote our clinical research activities abroad and/or to obtain necessary permits, licenses, and other regulatory approvals. We can be held liable for the corrupt or other illegal activities of these ~~third‑party~~third-party intermediaries, our employees, representatives, contractors, partners, and agents, even if we do not explicitly authorize or have actual knowledge of such activities.

Noncompliance with ~~anti‑corruption~~anti-corruption and ~~anti‑money~~anti-money laundering laws could subject us to whistleblower complaints, investigations, sanctions, settlements, prosecution, other enforcement actions, disgorgement of profits, significant fines, damages, other civil and criminal penalties or injunctions, suspension and/or debarment from contracting with certain persons, the loss of export privileges, reputational harm, adverse media coverage, and other collateral consequences. If any subpoenas, investigations, or other enforcement actions are launched, or governmental or other sanctions are imposed, or if we do not prevail in any possible civil or criminal litigation, our business, results of operations and financial condition could be materially harmed. In addition, responding to any action will likely result in a materially significant diversion of management’s attention and resources and significant defense and compliance costs and other professional fees. In certain cases, enforcement authorities may even cause us to appoint an independent compliance monitor which can result in added costs and administrative burdens.

If we or our ~~third~~‑~~party~~third-party manufacturers fail to comply with environmental, health and safety laws and regulations, we could become subject to fines or penalties or incur costs that could harm our business.

We and our ~~third‑party~~third-party manufacturers are subject to numerous environmental, health and safety laws and regulations, including those governing laboratory procedures and the handling, use, storage, treatment and disposal of hazardous materials and wastes. From time to time and in the future, our operations may involve the use of hazardous and flammable materials, including chemicals and biological materials, and produce hazardous waste products. We cannot eliminate the risk of contamination or injury from these materials. In the event of contamination or injury resulting from our use of hazardous materials, we could be held liable for any resulting damages, and any liability could exceed our ~~resources.~~resources and any coverage provided by our insurance. We also could incur significant costs associated with civil or criminal fines and penalties for failure to comply with such laws and regulations.

Although we maintain workers’ compensation insurance to cover us for costs and expenses we may incur due to injuries to our employees resulting from the use of hazardous materials, this insurance may not provide adequate coverage against potential liabilities. We do not maintain insurance for environmental liability or toxic tort claims that may be asserted against us.

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In addition, we may incur substantial costs in order to comply with current or future environmental, health and safety laws and regulations. These current or future laws and regulations may impair our research, development or production efforts. Our failure to comply with these laws and regulations also may result in substantial fines, penalties or other sanctions.

Further, with respect to the operations of our ~~third‑party~~third-party contract manufacturers, it is possible that if they fail to operate in compliance with applicable environmental, health and safety laws and regulations or properly dispose of wastes associated with our product candidates or products, we could be held liable for any resulting damages, suffer reputational harm or experience a disruption in the manufacture and supply of our product candidates or products.

Risks Related to Employee Matters and Managing Our Operations

We are ~~in the process~~a development-stage company with a limited number of ~~implementing a substantial reduction in personnel,which could disrupt our operations.In addition,~~employees and we may experience difficulties in retaining key employees ~~that we have identified for retention.~~and consultants.

~~In December 2016, following our receipt and announcement~~We are a development-stage company with a total of ~~initial, top-line results from our pivotal OPH1002 and OPH1003 Fovista trials for the treatment~~35 full-time employees as of ~~wet AMD, we announced that we had determined to implement a reduction in~~

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~~personnel to focus on an updated business plan. This reduction in personnel involves approximately 80%~~April 30, 2019. These employees support key areas of our ~~pre-announcement workforce~~business and includes personnel from nearly every department. During the first nine months of 2017, our workforce has been reduced by 112 employees in connection with the reduction in personnel and natural attrition. We expect to complete the reduction in personnel during the fourth quarter of 2017. Although we are reducing our personnel substantially, we are continuing to function as a development company and need to continue all or nearly all of our prior business functions to support such development,operations, including clinical operations, regulatory affairs, drug safety, data management, outsourced manufacturing and supply chain management, analytical development and quality assurance, as well as all of our general and administrative functions and public company infrastructure. Due to our limited financial resources and the inherent challenges associated with managing such a reduction in personnel, we may not be able to manage effectively the reduction in personnel and transition of operations to remaining employees.

~~Notwithstanding the reduction in personnel, we~~We remain highly dependent on David R. Guyer, M.D., our ~~Executive Chairman,~~executive chairman, and Glenn P. Sblendorio, our ~~Chief Executive Officer~~chief executive officer and ~~President,~~president, as well as the other principal members of our management, scientific and clinical teams. We do not maintain “key person” insurance for any of our executives or other employees. Although we have entered into letter agreements with our executive officers, each of them and our non-executive employees may terminate their employment with us at any time. As a result, key employees that we expect to retain ~~through specific dates~~ to assist with ~~transition activities~~the growth of our business may choose not to remain employees. In addition, we may experience difficulties in retaining key employees ~~that we have identified~~ for ~~retention, given the change in prospects for our company as well as other challenges.~~any number of reasons. The loss of the services of our executive officers or other key employees could impede the achievement of our research, development and commercialization objectives and seriously harm our ability to successfully implement our ~~updated~~ business ~~strategy.~~ plan.

Furthermore, replacing any such executive officers and key employees may be difficult and may take an extended period of time because of the limited number of individuals in our industry with the breadth of skills and experience required to successfully develop, gain marketing approval of and commercialize products. Competition to hire from this limited pool is intense, and we may be unable to hire, train, retain or motivate these key personnel on acceptable terms, if at all, given the competition among numerous pharmaceutical and biotechnology companies for similar ~~personnel.~~personnel, including, in particular, personnel with gene therapy experience. We also experience competition for the hiring of scientific and clinical personnel from universities and research institutions. In addition, we rely on consultants and advisors, including scientific and clinical advisors, to assist us in formulating our research and development, pipeline expansion and commercialization ~~strategy.~~strategies, including retaining key consultants previously used by Inception 4 for our HtrA1 inhibitor program and engaging and retaining key consultants with gene therapy experience. Our consultants and advisors may be employed by employers other than us and may have commitments under consulting or advisory contracts with other entities that may limit their availability to us. If we are unable to ~~strategically~~ attract or retain high quality personnel as we implement our ~~new~~ business plan, our ability to pursue our ~~development~~ strategy would be limited.

In connection with the reduction in personnel, we expect that we will incur approximately $13.3 million of aggregate pre-tax charges through the third quarter of 2017, of which approximately $12.4 million in the aggregate is expected to result in cash expenditures. As of September 30, 2017, our cash expenditures related to such reduction in personnel totaled $8.7 million. The reduction in personnel may divert our management’s time and attention. Any inability to manage the reduction in personnel could delay the execution of our updated business plan or disrupt our operations.

If we fail to establish and maintain effective internal control over financial reporting, our ability to accurately report our financial results could be adversely affected.

A material weakness is a deficiency, or combination of deficiencies, in internal control over financial reporting, such that there is a reasonable possibility that a material misstatement of the company’s annual or interim financial statements would not be prevented or detected on a timely basis. If any material weakness in our internal control over financial reporting is discovered or occurs in the future, our financial statements may contain material misstatements and we could be required to restate our financial results. As previously disclosed in July 2015, our management concluded that we experienced a material weakness in internal controls related to technical accounting expertise over the accounting for deferred tax assets and income tax accounting in general during certain prior financial reporting periods. The deficiency in the application of our controls relating to technical accounting expertise over the accounting for deferred tax assets and income tax accounting in general resulted in the audit committee of our board of directors concluding that the relevant financial statements should not be relied upon, and our subsequent restatement of the relevant financial statements.

During the year ended December 31, 2015, we took the following steps to remediate the identified material weakness: we added staffing within our finance department and engaged a nationally recognized accounting firm, in each case, with technical expertise in the area of tax accounting and financial reporting. Our management concluded that the identified material

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weakness in internal control over financial reporting was fully remediated as of December 31, 2015. Although we have remediated this deficiency in internal control over financial reporting, we cannot be certain that the remedial measures that we took in the past or other measures we take in the future, especially in light of our decreased size as a result of the

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implementation of our ~~planned~~ reduction in personnel during the year ended on December 31, 2017, and the associated decrease in staffing in our accounting and finance areas, will ensure that we maintain adequate controls over our financial reporting going forward and, accordingly, additional material weaknesses could occur or be identified. Any additional material weaknesses or combination of deficiencies could materially and adversely affect our ability to provide timely and accurate financial information, and ~~the current and~~any future deficiencies may impact investors’ confidence in our internal controls and our company, which could cause our stock price to decline.

~~Risks Related to Information Technology~~

We rely significantly upon information technology and any failure, inadequacy, interruption or security lapse of that technology, including any cyber security incidents, could harm our ability to operate our business effectively.

In the ordinary course of our business, we and our third‑party contractors maintain sensitive data on our and their respective networks, including our intellectual property and proprietary or confidential business information relating to our business and that of our clinical trial participants and business partners. In particular, we rely on contract research organizations and other third parties to store and manage information from our clinical trials. The secure maintenance of this sensitive information is critical to our business and reputation. Despite the implementation of security measures, our internal computer systems and those of our third‑party contractors are vulnerable to damage from cyber‑attacks, computer viruses, unauthorized access, natural disasters, terrorism, war and telecommunication and electrical failures. In particular, we believe that companies and other entities and individuals have been increasingly subject to a wide variety of security incidents, cyber‑attacks and other attempts to gain unauthorized access to systems and information. These threats can come from a variety of sources, ranging in sophistication from an individual hacker to a state‑sponsored attack. Cyber threats may be generic, or they may be custom‑crafted against our information systems or those of our third‑party contractors. For information stored with our third‑party contractors, we rely upon, and the integrity and confidentiality of such information is dependent upon, the risk mitigation efforts such third‑party contractors have in place. In the recent past, cyber‑attacks have become more prevalent and much harder to detect and defend against. Our and our third‑party contractors’ respective network and storage applications may be subject to unauthorized access by hackers or breached due to operator error, malfeasance or other system disruptions. It is often difficult to anticipate or immediately detect such incidents and the damage caused by such incidents. System failures, data breaches and any unauthorized access or disclosure of our information or intellectual property could compromise our intellectual property and expose sensitive business information. System failures or accidents or security breaches could cause interruptions in our operations, and could result in a material disruption of our clinical and commercialization activities and business operations, in addition to possibly requiring substantial expenditures of resources to remedy. A data security breach could also lead to public exposure of personal information of our clinical trial patients and others. Cyber‑attacks could cause us to incur significant remediation costs, result in product development delays, disrupt key business operations and divert attention of management and key information technology resources. The loss of clinical trial data could result in delays in our regulatory approval efforts and significantly increase our costs to recover or reproduce the data. To the extent that any disruption or security breach were to result in a loss of, or damage to, our data or applications, or inappropriate public disclosure of confidential or proprietary information, we could incur liability and our product research, development and commercialization efforts could be delayed.

Risks Related to Our Common Stock

Provisions in our corporate charter documents and under Delaware law could make an acquisition of us, which may be beneficial to our stockholders, more difficult and may prevent attempts by our stockholders to replace or remove members of our ~~current~~board of directors and management.

Provisions in our certificate of incorporation and our ~~by‑laws~~by-laws may discourage, delay or prevent a merger, acquisition or other change in control of our company that stockholders may consider favorable, including transactions in which our stockholders might otherwise receive a premium for their shares. These provisions could also limit the price that investors might be willing to pay in the future for shares of our common stock, thereby depressing the market price of our common stock. In addition, because our board of directors is responsible for appointing the members of our management team, these provisions may frustrate or prevent any attempts by our stockholders to replace or remove our current management by making it more difficult for stockholders to replace members of our board of directors. Among other things, these provisions:

provide for a classified board of directors such that only one of three classes of directors is elected each year;

allow the authorized number of our directors to be changed only by resolution of our board of directors;

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limit the manner in which stockholders can remove directors from ~~the~~our board of directors;

provide for advance notice requirements for stockholder proposals that can be acted on at stockholder meetings and nominations to our board of directors;

require that stockholder actions must be effected at a duly called stockholder meeting and prohibit actions by our stockholders by written consent;

limit who may call stockholder meetings;

authorize our board of directors to issue preferred stock without stockholder approval, which could be used to institute a “poison pill” that would work to dilute the stock ownership of a potential hostile acquirer, effectively preventing acquisitions that have not been approved by our board of directors; and

require the approval of the holders of at least 75% of the votes that all our stockholders would be entitled to cast to amend or repeal certain provisions of our certificate of incorporation or ~~by‑laws.~~by-laws.

Moreover, because we are incorporated in Delaware, we are governed by the provisions of Section 203 of the Delaware General Corporation Law, which prohibits a person who owns in excess of 15% of our outstanding voting stock from merging or combining with us for a period of three years after the date of the transaction in which the person acquired in excess of 15% of our outstanding voting stock, unless the merger or combination is approved in a prescribed manner.

The price of our common stock may be volatile and fluctuate substantially, which could result in substantial losses for stockholders.

Our stock price may be volatile and could be subject to wide fluctuations in response to various factors, some of which are beyond our control. The stock market in general, and the market for smaller pharmaceutical and biotechnology companies in particular, have experienced extreme volatility that has often been unrelated to the operating performance of particular companies. As a result of this volatility, our stockholders may not be able to sell their shares of common stock at or above the price at which they purchased their shares. The market price for our common stock may be influenced by many factors, including:

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results of research, preclinical development activities and clinical trials for our product candidates and the timing of the receipt of such results;

the success of products or technologies that compete with our product candidates, including results of clinical trials of product candidates of our competitors;

~~results of clinical trials for our product candidates and the timing of the receipt of such results;~~

the results of our efforts to ~~in‑license~~in-license or acquire the rights to other ~~products,~~ product candidates and technologies for the treatment of ~~ophthalmic~~retinal diseases;

~~political, regulatory or legal developments in the United States and other countries;~~

developments or disputes concerning patent applications, issued patents or other proprietary rights;

the recruitment or departure of key personnel;

the level of expenses related to any of our product candidates or ~~clinical~~ development programs;

actual or anticipated changes in estimates as to financial results, development timelines or recommendations by securities analysts;

variations in our financial results or those of companies that are perceived to be similar to us;

changes in the structure of healthcare payment systems;

market conditions in the pharmaceutical and biotechnology sectors;

general economic, industry and market conditions;

political, regulatory or legal developments in the United States and

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other countries; and

the other factors described in this “Risk Factors” section.

For example, following our announcement of initial, top-line results from our ~~pivotal OPH1002 and OPH1003 Fovista trials~~OPH2007 Phase 2a clinical trial for Zimura in combination with the anti-VEGF agent Lucentis for the treatment of wet AMD, the closing price of our common stock declined from ~~$38.77~~$2.22 on ~~December~~November 9, ~~2016~~2018 to ~~$5.29~~$1.92 on ~~December 12, 2016~~November 14, 2018 and declined further ~~declined to $2.82~~thereafter. The closing price of our common stock was $1.43 on ~~September 29, 2017.~~May 6, 2019. Following periods of volatility in the market price of a company’s stock, securities ~~class‑action~~class-action litigation has often been instituted against that company. WeFor example, we and certain of our current and former executive officers have been named as defendants in purported class action lawsuits following our announcement in December 2016 of the initial, top-line ~~results.~~results from the first two of our Phase 3 Fovista trials for the treatment of wet AMD. See ~~“Part~~Part II, Item ~~1-Legal Proceedings”~~1 of this Quarterly Report on Form 10-Q and ~~“-Risks~~in this "Risk Factors" section, “Risks Related to Our ~~Updated~~ Business Plan, Financial Position and Need for Additional ~~Capital-We~~Capital—We and certain of our current and former executive officers have been named as defendants in lawsuits that could result in substantial costs and divert management’s ~~attention.~~attention.” These proceedings and other similar litigation, if instituted against us, could cause us to incur substantial costs to defend such claims and divert management’s attention and resources, which could seriously harm our business.

If a significant portion of our total outstanding shares are sold into the market, the market price of our common stock could drop significantly, even if our business is doing well.

Sales of a substantial number of shares of our common stock in the public market could occur at any time. These sales, or the perception in the market that the holders of a large number of shares intend to sell shares, could reduce the market price of our common stock. For example, we issued 5,174,727 shares of our common stock to the former equityholders of Inception 4 as upfront consideration for our acquisition of Inception 4. These shares are subject to lock-up restrictions, which expired at the end of April 2019 with respect to 50% of such shares, and will expire at the end of October 2019 with respect to the remaining 50% of such shares, following which such shares may be freely sold and traded pursuant to a registration statement on Form S-3 (File No. 333-229978) that was declared effective by the Securities and Exchange Commission on April 25, 2019. If the holders of these shares sell, or the market perceives that these holders will sell, the shares currently held by them, the price of our common stock may decline.

Moreover, we have filed, and expect to continue to file, registration statements on Form ~~S‑8~~S-8 registering all shares of common stock that we may issue under our equity compensation plans. Once registered on Form ~~S‑8,~~S-8, shares underlying these

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equity awards can be freely sold in the public market upon issuance, subject to volume, notice and manner of sale limitations applicable to affiliates.

We incur increased costs as a result of operating as a public company, and our management is required to devote substantial time to compliance initiatives and corporate governance practices.

As a public company, we incur and will continue to incur significant legal, accounting and other expenses that we did not incur as a private company. The ~~Sarbanes‑Oxley~~Sarbanes-Oxley Act of 2002, the ~~Dodd‑Frank~~Dodd-Frank Wall Street Reform and Consumer Protection Act, the listing requirements of The ~~NASDAQ~~Nasdaq Global Select Market and other applicable securities rules and regulations impose various requirements on public companies, including establishment and maintenance of effective disclosure and financial controls and corporate governance practices. Our management and other personnel devote a substantial amount of time to these compliance initiatives. Moreover, these rules and regulations have increased our legal and financial compliance costs and have made some activities more ~~time‑consuming~~time-consuming and costly.

Pursuant to Section 404 of the ~~Sarbanes‑Oxley~~Sarbanes-Oxley Act of 2002, or Section 404, we are required to furnish with our periodic Exchange Act reports a report by our management on our internal control over financial reporting. We are also required to include with our annual report an attestation report on internal control over financial reporting issued by our independent registered public accounting firm. To achieve compliance with Section 404, we must document and evaluate our internal control over financial reporting, which is both costly and challenging. In this regard, we will need to continue to dedicate internal resources and engage outside consultants to assess and document the adequacy of internal control over financial reporting, continue steps to improve control processes as appropriate, validate through testing that controls are functioning as documented and implement a continuous reporting and improvement process for internal control over financial reporting. There is a risk that our internal control over financial reporting may, in the future, be found to be ineffective under Section 404. Our identification of one or more material weaknesses could result in an adverse reaction in the financial markets due to a loss of confidence in the reliability of our financial statements.

Because we do not anticipate paying any cash dividends on our common stock in the foreseeable future, capital appreciation, if any, will be our stockholders’ sole source of gain.

We have never declared or paid cash dividends on our common stock. We currently intend to retain all of our future earnings, if any, to finance the growth ~~and development~~ of our business. In addition, the terms of any future debt agreements that we may enter into may preclude us from paying dividends. As a result, capital appreciation, if any, of our common stock will be our stockholders’ sole source of gain for the foreseeable future.

Item 2. Unregistered Sales of Equity Securities and Use of Proceeds.

Recent Sales of Unregistered Securities

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We did not sell any unregistered equity securities during the period covered by this Quarterly Report on Form 10-Q.

Purchase of Equity Securities

We did not purchase any of our registered equity securities during the period covered by this Quarterly Report on Form 10-Q.

Item 5. Other ~~Information.~~

Information

None.

PART IV

Item 6. ~~Exhibits.~~Exhibits and Financial Statement Schedules

The exhibits filed as part of this Quarterly Report on Form 10-Q are set forth on the Exhibit Index, which is incorporated herein by reference.

~~EXHIBIT INDEX~~(2) Financial Statement Schedules

No financial statement schedules have been filed as part of this Quarterly Report on Form 10-Q because they are not applicable, not required or because the information is otherwise included in our financial statements or notes thereto.

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(3) Exhibits



Exhibit Number		Description of Exhibit
3.1		Restated Certificate of Incorporation of the Registrant (incorporated by reference to Exhibit 3.3 to Amendment No. 2 of the Registrant's Registration Statement on Form S-1 (File No. 333-190643) filed with the SEC on September 9, 2013)
3.2		Certificate of Amendment to Restated Certificate of Incorporation of the Registrant (incorporated by reference to Exhibit 3.1 of the Registrant's Current Report on Form 8-K filed with the SEC on April 16, 2019)
~~3.2~~ 3.3		Amended and Restated Bylaws of the Registrant (incorporated by reference to Exhibit 3.4 to Amendment No. 2 of the Registrant's Registration Statement on Form S-1 (File No. 333-190643) filed with the SEC on September 9, 2013)

10.1*		~~Letter Agreement between the Registrant and Novartis Pharma AG, dated July 3, 2017~~31.1

~~31.1~~		Certification of ~~Principal Executive Officer~~principal executive officer pursuant to Rule 13a-14(a) ~~or Rule~~ /15d-14(a) of the Securities Exchange Act of 1934, as ~~adopted pursuant to Section 302 of the Sarbanes-Oxley Act of 2002~~amended

31.2		Certification of ~~Principal Financial Officer~~principal financial officer pursuant to Rule 13a-14(a) ~~or Rule~~ /15d-14(a) of the Securities Exchange Act of 1934, as ~~adopted pursuant to Section 302 of the Sarbanes-Oxley Act of 2002~~amended

32.1		Certification of ~~Principal Executive Officer~~principal executive officer pursuant to 18 U.S.C. ~~Section 1350,~~§1350, as adopted pursuant to Section 906 of the Sarbanes-Oxley Act of 2002

32.2		Certification of ~~Principal Financial Officer~~principal financial officer pursuant to 18 U.S.C. ~~Section 1350,~~§1350, as adopted pursuant to Section 906 of the Sarbanes-Oxley Act of 2002

101.INS**		XBRL Instance Document

101.SCH**		XBRL Taxonomy Extension Schema Document

101.CAL**		XBRL Taxonomy ~~Extension~~ Calculation Linkbase Document

101.DEF**		XBRL Taxonomy Extension Definition Linkbase Document

101.LAB**		XBRL Taxonomy ~~Extension Labels~~Label Linkbase Document

101.PRE**		XBRL Taxonomy ~~Extension~~ Presentation Linkbase Document



*		Submitted electronically herewith.

* Confidential treatment has been requested as to certain portions, which have been omitted and separately filed with the Securities and Exchange Commission.

** Submitted electronically herewith.

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Attached as Exhibit 101 to this report are the following formatted in XBRL (Extensible Business Reporting Language): (i) Consolidated Balance Sheets at ~~September 30, 2017~~March 31, 2019 (unaudited) and December 31, ~~2016 (unaudited),~~2018, (ii) Consolidated Statements of Operations and Comprehensive Loss (unaudited) for the three ~~and nine~~ month periods ended ~~September 30, 2017~~March 31, 2019 and ~~2016,~~2018, (iii) Consolidated Statements of Stockholders' Equity (unaudited) for the three month periods ended March 31, 2019 and 2018, (iv) Consolidated Statements of Cash Flows (unaudited) for ~~the nine~~three month ~~period~~periods ended ~~September 30, 2017~~March 31, 2019 and ~~2016~~2018 and ~~(iv)~~(v) Notes to Financial Statements (unaudited).

In accordance with Rule 406T of Regulation S-T, the XBRL related information in Exhibit 101 to this Quarterly Report on Form 10-Q is deemed not filed or part of a registration statement or prospectus for purposes of Sections 11 or 12 of the Securities Act, is deemed not filed for purposes of Section 18 of the Exchange Act, and otherwise is not subject to liability under these sections.

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SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned thereunto duly authorized.



	~~OPHTHOTECH CORPORATION~~IVERIC bio, Inc.


Date: ~~November~~May 8, ~~2017~~2019	By:	/s/ David F. Carroll
		David F. Carroll
		Chief Financial Officer
		(Principal Financial and Accounting Officer)



PART I—FINANCIAL INFORMATION

Item 1.	Financial Statements	3
	Unaudited Consolidated Balance Sheets	3
	Unaudited Consolidated Statements of Operations and Comprehensive Loss	4
	Unaudited Consolidated Statements of Stockholders' Equity	5
	Unaudited Consolidated Statements of Cash Flows	6
	Notes to Unaudited Consolidated Financial Statements	7
Item 2.	Management’s Discussion and Analysis of Financial Condition and Results of Operations	2420
Item 3.	Quantitative and Qualitative Disclosures About Market Risk	4334
Item 4.	Controls and Procedures	4334

			PART II—OTHER INFORMATION

Item 1.	Legal Proceedings	4536
Item 1A.	Risk Factors	4537
Item 2.	Unregistered Sales of Equity Securities and Use of Proceeds	8279
Item 5.	Other Information	8379
Item 6.	Exhibits	8379
	Signatures	80



	As of December 31, 2016
	Cost		Unrealized Gains		Unrealized Losses			Fair Value

U.S. Treasury securities	$	120,288	$	6	$	(33	)	$	120,261
Corporate debt securities	35,114		—		(27		)	35,087
Total	$	155,402	$	6	$	(60	)	$	155,348



	Common Stock Options		Weighted Average Exercise Price

Outstanding, December 31, 2016	3,359		$	39.92
Granted	1,294		$	4.25
Exercised	(20	)	$	1.64
Expired or forfeited	(995	)	$	38.79
Outstanding, September 30, 2017	3,638		$	27.74

Options exercisable at September 30, 2017			1,839
Weighted average grant date fair value (per share) of options granted during the period			$	2.95



			As of September 30, 2017
			Options Outstanding			Options Exercisable
Range of Exercise Prices	Total Options Outstanding		Weighted Average Remaining Life (Years)	Weighted Average Exercise Price		Number Exercisable		Weighted Average Exercise Price

$0.12-$10.03	1,364		8.8	$	4.63	194		$	6.93
$10.04-$20.00	204		5.7	$	13.52	147		$	13.63
$20.01-$30.00	127		6.1	$	25.13	122		$	25.14
$30.01-$40.00	836		5.8	$	32.81	759		$	32.89
$40.01-$55.00	727		7.8	$	46.47	431		$	46.11
$55.01-$73.22	380		8.3	$	72.18	186		$	71.13
	3,638		7.6	$	27.74	1,839		$	35.07

Aggregate Intrinsic Value	$	114				$	95



	Restricted Stock Units		Weighted Average Grant-Date Fair Value

Outstanding, December 31, 2016	721		$	55.33
Awarded	248		$	4.42
Vested	(263	)	$	24.24
Forfeited	(288	)	$	50.17
Outstanding, September 30, 2017	418		$	42.85



	Useful Life (Years)	September 30, 2017			December 31, 2016

Manufacturing and clinical equipment	7 - 10	$	412		$	617
Computer, software and other office equipment	5	1,711			1,711
Furniture and fixtures	1 - 7	774			774
Leasehold improvements	1 - 5	1,835			1,835
		4,732			4,937
Accumulated depreciation		(3,430		)	(1,656		)
Property and equipment, net		$	1,302		$	3,281



	Accrued Severance and Other Employee Costs
Beginning Balance	$	—
Accrued restructuring expenses	11,076
Payments	(8,727		)
Ending Balance	$	2,349



	Payments Due by Period
	Total		Less than 1 year		1-3 years		3-5 years		More than 5 years
	(in thousands)
Operating Leases (1)	$	814	$	814	$	—	$	—	$	—
Severance and Other Employee Benefits (2)	3,679		3,679		—		—		—
Total (3)	$	4,493	$	4,493	$	—	$	—	$	—