Common Stock

Additional
Paid-In

Accumulated
Other
Comprehensive

Accumulated

Total
Stockholders’

Shares

Amount

Capital

Loss

Deficit

Equity

Balance at December 31, 2021

34,568,821

$
35

$
412,930

$
(149
)

$
(340,417
)

$
72,399

Issuance of common stock upon offering
   at-the-market, net of $1,288 of commissions

5,841,786

6

45,604

—

—

45,610

Issuance of common stock upon exercise
   of stock options

15,995

—

144

—

—

144

Vesting of common stock issued under
   Product Development Agreement

—

—

19

—

—

19

Issuance of common stock upon ESPP purchase

18,130

—

64

—

—

64

Issuance of common stock upon release of restricted
   stock units

85,106

—

—

—

—

—

Stock-based compensation expense

—

—

2,047

—

—

2,047

Unrealized loss on available-for-sale debt
   securities, net

—

—

—

(373
)

—

(373
)
Net loss

—

—

—

—

(22,643
)

(22,643
)
Balance at March 31, 2022

40,529,838

$
41

$
460,808

$
(522
)

$
(363,060
)

$
97,267


	Common Stock			Additional Paid-In Capital		Accumulated Other Comprehensive Income (Loss)		Accumulated Deficit		Total Stockholders’ Equity
	Shares	Amount
Balance at December 31, 2022	44,074,284	$	44	$	492,759	$	(300)	$	(437,193)	$	55,310
Issuance of common stock upon ESPP purchase	29,986	—		41		—		—		41
Issuance of common stock upon release of restricted stock units and performance stock units	192,147	—		—		—		—		—
Stock-based compensation expense	—	—		2,542		—		—		2,542
Unrealized gain on available-for-sale debt securities, net	—	—		—		167		—		167
Cumulative translation adjustment	—	—		—		(37)		—		(37)
Net loss	—	—		—		—		(22,784)		(22,784)
Balance at March 31, 2023	44,296,417	$	44	$	495,342	$	(170)	$	(459,977)	$	35,239

	Three Months Ended
	March 31,							Three Months Ended March 31,
	2022			2021				2023		2022
Operating activities							Operating activities
Net (loss) income	$	(22,643	)	$	29,248
Adjustments to reconcile net (loss) income to net cash used in operating activities:
Gain from sale of priority review voucher		—			(46,493	)
Income related to asset purchase agreement		—			(281	)
Net loss							Net loss	$	(22,784)	$	(22,643)
Adjustments to reconcile net loss to net cash used in operating activities:							Adjustments to reconcile net loss to net cash used in operating activities:
Depreciation and amortization		73			67		Depreciation and amortization	74		73
Stock-based compensation		2,047			1,549
Inventory write down							Inventory write down	10		—
Amortization of debt securities premiums and discounts		330			191		Amortization of debt securities premiums and discounts	(374)		330
Non-cash interest expense		200			199		Non-cash interest expense	364		200
Amortization of operating lease right-of-use assets		132			127
Reduction in the carrying amount of right-of-use assets							Reduction in the carrying amount of right-of-use assets	115		132
Common stock issued under Product Development Agreement		19			53		Common stock issued under Product Development Agreement	—		19
Stock-based compensation							Stock-based compensation	2,542		2,047
Change in operating assets and liabilities:							Change in operating assets and liabilities:
Accounts receivable		289			(639	)	Accounts receivable	(2,130)		289
Inventories		666			(1,304	)	Inventories	(860)		666
Prepaid expenses and other current assets		(854	)		1,529		Prepaid expenses and other current assets	1,401		(854)
Other assets		(397	)		(18	)	Other assets	454		(397)
Accounts payable		1,269			3,175		Accounts payable	1,553		1,269
Accrued liabilities		560			(2,205	)	Accrued liabilities	(4,232)		560
Operating lease liabilities		(150	)		(131	)	Operating lease liabilities	(138)		(150)
Net cash used in operating activities		(18,459	)		(14,933	)	Net cash used in operating activities	(24,005)		(18,459)
Investing activities							Investing activities
Purchase of debt securities available-for-sale		(10,902	)		(2,049	)	Purchase of debt securities available-for-sale	(19,388)		(10,902)
Proceeds from maturities of debt securities available-for-sale		7,900			49,755		Proceeds from maturities of debt securities available-for-sale	32,987		7,900
Proceeds from sale of priority review voucher		—			95,000
Payments related to priority review voucher		—			(48,507	)
Proceeds related to asset purchase agreement		—			281
Purchase of property and equipment		—			(16	)	Purchase of property and equipment	(216)		—
Net cash (used in) provided by investing activities		(3,002	)		94,464
Net cash provided by (used in) investing activities							Net cash provided by (used in) investing activities	13,383		(3,002)
Financing activities							Financing activities
Issuance of common stock upon offering at-the-market, net of commissions		45,610			—		Issuance of common stock upon offering at-the-market, net of commissions	—		45,610
Proceeds from issuance of common stock upon stock option exercises		144			166		Proceeds from issuance of common stock upon stock option exercises	—		144
Proceeds from issuance of common stock upon ESPP purchase		64			146		Proceeds from issuance of common stock upon ESPP purchase	41		64
Common stock offering costs		(16	)		(122	)	Common stock offering costs	—		(16)
Payment of debt issuance costs		—			(175	)
Net cash provided by financing activities		45,802			15		Net cash provided by financing activities	41		45,802
Net increase in cash and cash equivalents		24,341			79,546
Effect of foreign exchange on cash and cash equivalents							Effect of foreign exchange on cash and cash equivalents	(36)		—
Net (decrease) increase in cash and cash equivalents							Net (decrease) increase in cash and cash equivalents	(10,617)		24,341
Cash and cash equivalents at beginning of period		22,221			28,864		Cash and cash equivalents at beginning of period	25,798		22,221
Cash and cash equivalents at end of period	$	46,562		$	108,410		Cash and cash equivalents at end of period	$	15,181	$	46,562

Supplemental disclosure of cash flow information:							Supplemental disclosure of cash flow information:
Interest paid	$	686		$	686		Interest paid	$	920	$	686
Income taxes paid	$	41		$	—		Income taxes paid	$	—	$	41

In June 2021, the French National Agency for Medicines and Health Products Safety (ANSM) granted Zokinvy (lonafarnib) a Temporary Authorizations for Use (Autorisation Temporaire d'Utilisation or ATU) for an early access program for a term of one year. The Company has received a one year extension of the ATU program and expects the program to continue until commercial reimbursement of Zokinvy is approved in France. In the context of this program, the Company sells product to a distributor who in turn ships product to pharmacies after receiving requests from physicians for patients in France. In November 2021, the Company began distributing and recognizing revenue from sales of Zokinvy (lonafarnib) through a reimbursed early access program in France. The Company recorded revenue of $0.5 million from sales of product under the ATU program for the three months ended March 31, 2023. There was 0no revenue from sale of product under the ATU program for the three months ended March 31, 2022.

The following tables present the fair value hierarchy for assets and liabilities measured at fair value (in thousands):

During the three months ended March 31, 2023 and 2022, ~~and 2021,~~ the weighted-average grant date fair value of options granted were ~~$3.23~~$1.48 and ~~$7.76~~$3.23 per share, respectively.

Rent expense recognized for the Company’s operating leases was $0.1 million ~~and $0.2 million~~ for the three months ended March 31, ~~2022~~2023 and ~~2021, respectively.~~2022. Under the terms of the lease agreements, the Company is also responsible for certain variable lease payments that are not included in the measurement of the lease liability. Variable lease payments for the operating leases ~~was~~were $15,000 and $23,000 for ~~each of~~ the three months ended March 31, 2023 and 2022, ~~and 2021.~~

The following table sets forth the outstanding potentially dilutive securities which have been excluded in the calculation of diluted net ~~(loss) income~~loss per share because including such securities would be anti-dilutive (in common stock equivalent shares):

~~On March 25, 2022, the Company entered into a new Open Market Sale Agreement~~^SM with Jefferies, pursuant to which the Company can sell up to a maximum of $50.0 million of common stock in offerings that are deemed “at the market” offerings as defined in Rule 415 under the Securities Act, under Eiger’s effective shelf registration statement (the 2022 ATM Facility). In April 2022, the Company completed offerings from the 2022 ATM Facility for a total of 2,686,288 shares of common stock resulting in net proceeds of $20.8 million, after deducting commissions costs

Below is a summary of material factors that make an investment in our common stock speculative or risky. Importantly, this summary does not address all of the risks and uncertainties that we face. Additional discussion of the risks and uncertainties summarized in this risk factor summary, as well as other risks and uncertainties that we face, can be found under “Risk Factors” in Part I,II, Item 1A of this Quarterly ~~Report on Form 10-Q.~~Report. The below summary is qualified in its entirety by that more complete discussion of such risks and uncertainties. You should carefully consider the risks and uncertainties described under “Risk Factors” in Part II, Item 1A of this Quarterly Report ~~on Form 10-Q~~ as part of your evaluation of an investment in our common stock.

•	~~Ability to file EUA~~

•We are a commercial-stage biopharmaceutical company with additional product candidates in clinical development and a limited operating history. We have incurred net losses in each year since our inception. We have one U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA)-approved product for commercial sale, Zokinvy (lonafarnib), and prior to 2021, have never generated any product revenue and may never be profitable.•

~~No renewal of determination that a public health emergency exists as a result of COVID-19 by Secretary of Health and Human services.~~

•

We are a commercial-stage biopharmaceutical company with additional product candidates in clinical development and a limited operating history. We have incurred net losses in each year since our inception. We have one FDA-approved product for commercial sale, Zokinvy (lonafarnib), and prior to 2021, have never generated any product revenue and may never be profitable.

•

We are dependent on the success of our product candidates, which are in various stages of clinical development. We cannot give any assurance that we will generate data for any of our product candidates sufficient to receive regulatory approval and without regulatory approval we will not be able to market our product candidates.

•

~~Prior to the approval of our new drug application (NDA) for Zokinvy~~Ò (lonafarnib) to reduce the risk of mortality in Progeria, and for treatment of processing-deficient progeroid laminopathies with either heterozygous LMNA mutation with progerin-like protein accumulation, or homozygous or compound heterozygous ZMPSTE24 mutations, we had not submitted an application for approval or obtained U.S. Food and Drug Administration (FDA)•Prior to the approval of our new drug application (NDA) for Zokinvy® (lonafarnib) to reduce the risk of mortality in HGPS, and for treatment of processing-deficient progeroid laminopathies with either heterozygous LMNA mutation with progerin-like protein accumulation, or homozygous or compound heterozygous ZMPSTE24 mutations, we had not submitted an application for approval or obtained FDA approval for any product. We may not be able to obtain FDA approval of any future NDA or Biologics License Application (BLA) for our product candidates, which would prohibit commercialization.

•Our business strategy is based upon obtaining and maintaining Orphan Drug designation for our product candidates. If we are unable to obtain or maintain Orphan Drug designation or regulatory approval, our business would be substantially harmed.•

Our Marketing Authorization Application (MAA) for Zokinvy is currently under review by the European Medicines Agency (EMA), rejection of which would mean that we cannot commercialize Zokinvy in the European Economic Area.

•Our future success depends in part on our ability to attract, retain, and motivate qualified personnel.•

Our business strategy is based upon obtaining and maintaining Orphan Drug designation for our product candidates. If we are unable to obtain Orphan Drug designation or regulatory approval, our business would be substantially harmed.

•	~~Drug~~•Product development involves a lengthy and expensive process with an uncertain outcome, and results of earlier studies may not be predictive of future study results.

•	We rely on clinical studies of our product candidates in order to obtain regulatory approval. We may find it difficult to enroll patients in our clinical studies given the limited number of patients who have the diseases for which our product candidates are being studied.

•If clinical studies of our product candidates fail to demonstrate safety, efficacy, purity and/or potency to the satisfaction of the FDA or similar regulatory authorities outside the United States or do not otherwise produce positive results, we may incur additional costs or experience delays in completing, or ultimately be unable to complete, the development and commercialization of our product candidates.

•We rely on third parties to conduct our clinical studies, manufacture our product candidates and perform other services. Our ability to obtain regulatory approval or commercialize our product candidates and our business could be impaired if these collaborations are unsuccessful.•

If clinical studies of our product candidates fail to demonstrate safety and efficacy to the satisfaction of the FDA or similar regulatory authorities outside the United States or do not otherwise produce positive results, we may incur additional costs or experience delays in completing, or ultimately be unable to complete, the development and commercialization of our product candidates.

•If the market opportunities for our product candidates are smaller than we believe they are, we may not meet our revenue expectations. Because the patient populations in the market for our product candidates may be small, we must be able to successfully identify patients and acquire a significant market share to achieve profitability and growth.•

We rely on third parties to conduct our clinical studies, manufacture our product candidates and perform other services. Our ability to obtain regulatory approval or commercialize our product candidates and our business could be impaired if these collaborations are unsuccessful.

•We face intense competition and rapid technological change and the possibility that our competitors may develop therapies that are similar, more advanced or more effective than ours.•

If the market opportunities for our product candidates are smaller than we believe they are, we may not meet our revenue expectations. Because the patient populations in the market for our product candidates may be small, we must be able to successfully identify patients and acquire a significant market share to achieve profitability and growth.

•We currently have limited marketing and sales capabilities for the commercialization of our product candidates.•

~~We face intense competition and rapid technological change and the possibility that our competitors may develop therapies that are similar, more advanced or more effective than ours.~~

•The commercial success of any of our current or future product candidates will depend upon the degree of market acceptance by physicians, patients, third-party payors and others in the medical community. Sales of our products depend substantially on the extent to which the costs of our product candidates will be paid for or reimbursed by healthcare management organizations or government authorities or third-party payors.•

~~We currently have limited marketing and sales capabilities for the commercialization of our product candidates.~~

•We are currently conducting and will continue to conduct clinical trials for our product candidates outside the United States, which could expose us to risks that could have a material adverse effect on our business, including risks in connection with the actions taken by the Russian Federation in Ukraine and surrounding areas.•

The commercial success of any of our current or future product candidates will depend upon the degree of market acceptance by physicians, patients, third-party payors and others in the medical community. Sales of our products depend substantially on the extent to which the costs of our product candidates will be paid for or reimbursed by healthcare management organizations or government authorities or third-party payors.

•We may not be able to develop peginterferon lambda for COVID-19 or file for a temporary use authorization with a foreign regulatory agency.•

We are currently conducting and will continue to conduct clinical trials for our product candidates outside the United States, which could expose us to risks that could have a material adverse effect on our business, including risks in connection with the recent actions taken by the Russian Federation in Ukraine and surrounding areas.

•	We intend to rely on a combination of exclusivity from Orphan Drug designation and our patent rights for our product candidates. If we are unable to maintain exclusivity from the combination of these approaches, then our ability to compete effectively in our markets may be harmed.

•The annual reassessment by the EMA of the risk-benefit balance for Zokinvy including information on the safe and effective use may not be positive, which could lead to a variation, suspension, revocation of our marketing authorization or requirement to fulfil additional specific obligations.•

If we are unable to maintain effective proprietary rights for our product candidates, or if the scope of the intellectual property protection is not sufficiently broad, our competitors could develop and commercialize product candidates similar or identical to ours.

•If we are unable to maintain effective proprietary rights for our product candidates, or if the scope of the intellectual property protection is not sufficiently broad, our competitors could develop and commercialize product candidates similar or identical to ours.•

We may be unsuccessful in obtaining or maintaining necessary rights to our product candidates through acquisitions and in-licenses. If we fail to comply with obligations in the agreements under which we license intellectual property and other rights from third parties or otherwise experience disruptions to our business relationships with our licensors, we could lose license rights that are important to our business.

•	~~We may not be successful in any efforts to identify, license, discover, develop or commercialize additional product candidates.~~

•We may be unsuccessful in obtaining or maintaining necessary rights to our product candidates through acquisitions and in-licenses. If we fail to comply with obligations in the agreements under which we license intellectual property and other rights from third parties or otherwise experience disruptions to our business relationships with our licensors, we could lose license rights that are important to our business.•

~~Healthcare~~ ~~legislative reform measures may have a material adverse effect on our business and results of operations.~~ ~~If we fail to comply with environmental, health and safety laws and regulations, we could become subject to fines or penalties or incur costs.~~

•We may not be successful in any efforts to identify, license, discover, develop or commercialize additional product candidates.•

~~We face potential product liability, and, if successful claims are brought against us, we may incur substantial liability and costs.~~

•Healthcare legislative reform measures may have a material adverse effect on our business and results of operations. If we fail to comply with environmental, health and safety laws and regulations, we could become subject to fines or penalties or incur costs.•

We are dependent upon information technology systems and any failure or security breach of such systems could result in a material disruption in the development of our product candidates or other business operations as well as result in statutory or contractual obligations or otherwise expose us to liability.

•We face potential product liability, and, if successful claims are brought against us, we may incur substantial liability and costs.•

The current COVID-19 pandemic has and may continue to adversely affect our financial condition and our business as well as those of third parties on which we rely on significant manufacturing, clinical or other business operations.

•We are dependent upon information technology systems and any failure or security breach of such systems could result in a material disruption in the development of our product candidates or other business operations as well as result in statutory or contractual obligations or otherwise expose us to liability.

•Our future success depends in part on our ability to attract, retain, and motivate qualified personnel.

•The current COVID-19 pandemic has and may continue to adversely affect our financial condition and our business as well as those of third parties on which we rely on significant manufacturing, clinical or other business operations.

Risks Related to our Financial Condition, Integration and Capital Requirements

We have incurred losses since our inception, have a limited operating history on which to assess our business, and anticipate that we will continue to incur significant losses for the foreseeable future.

We are a commercial-stage biopharmaceutical company with a limited operating history. We have incurred net losses in each year since our inception. For the three months ended March 31, ~~2022~~2023 and ~~2021,~~2022, we reported a net loss of ~~$22.6~~$22.8 million and ~~net income of $29.2~~$22.6 million, respectively. As of March 31, ~~2022,~~2023, we had an accumulated deficit of ~~$363.1~~$460.0 million. Our prior losses, combined with expected future losses, have had and may continue to have an adverse effect on our stockholders’ equity and working capital.

We believe that our currently available resources will be sufficient to fund our planned operations for at least the next 12 months following the issuance date of these ~~condensed~~ consolidated financial statements. Our assumption does not reflect the possibility that we may not be able to access a portion of our existing cash, cash equivalents and short-term securities due to market and other conditions. For example, on March 10, 2023, the Federal Deposit Insurance Corporation (FDIC) was appointed receiver of Silicon Valley Bank (SVB), where we maintain an operating account with a balance that exceeded the FDIC insurance limit. Although, the cash in our accounts at Silicon Valley Bank did not impact our operations or our conclusion that we have sufficient capital to fund our operations for at least the next 12 months, we cannot be certain that future market corrections or other conditions will not impact our ability to access our cash, cash equivalents and short-term securities. On March 12, 2023, the U.S. Treasury Department, the Federal Reserve and the FDIC jointly announced enabling actions that fully protect all depositors of SVB and that such depositors would have access to all of their funds starting March 13, 2023. On March 26, 2023, the FDIC announced that First Citizens BancShares would acquire the commercial banking business of SVB. We continue to maintain an operating account at SVB and have begun measures to reduce our deposit concentration risk. If other banks and financial institutions enter receivership or become insolvent in the future in response to financial conditions affecting the banking system and financial markets, our ability to access our existing cash, cash equivalents and short-term securities may be threatened.

We expect to continue to incur significant expenses and increasing operating losses for the foreseeable future and our expenses will increase substantially if and as we:

•	~~continue the clinical development of our product candidates;~~

•	~~in-license or acquire additional~~•continue the clinical development of our product candidates;

•	~~undertake the manufacturing or have manufactured our~~•in-license or acquire additional product candidates;

•undertake the manufacturing or have manufactured our product candidates;•

~~advance our programs into larger, more expensive clinical studies;~~

•advance our programs into larger, more expensive clinical studies;•

~~initiate additional nonclinical, clinical, or other studies for our product candidates;~~

•initiate additional nonclinical, clinical, or other studies for our product candidates;•

~~commercialize and provide expanded access to Zokinvy for the treatment of Progeria and processing-deficient progeroid laminopathies~~

•commercialize and provide expanded access to Zokinvy for the treatment of HGPS and processing-deficient PL•

~~identify and develop potential commercial opportunities, such as lonafarnib boosted with ritonavir, peginterferon lambda for HDV, and avexitide for HI and PBH;~~

•identify and develop potential commercial opportunities, such as lonafarnib-based regimens and peginterferon lambda for HDV, and avexitide for HI and PBH;•

~~seek regulatory and marketing approvals and reimbursement for our product candidates;~~

•seek regulatory and marketing approvals and reimbursement for our product candidates;•

~~establish a sales, marketing, and distribution infrastructure to commercialize any products for which we may obtain marketing approval and market ourselves;~~

•establish a sales, marketing, and distribution infrastructure to commercialize any products for which we may obtain marketing approval and market ourselves;•

~~seek to identify, assess, acquire, and/or develop other product candidates;~~

•seek to identify, assess, acquire, and/or develop other product candidates;•

~~make milestone, royalty or other payments under third-party license agreements;~~

•make milestone, royalty or other payments under third-party license agreements;•

~~develop and educate HDV markets;~~

•develop and educate HDV markets;•

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

•seek to maintain, protect, and expand our intellectual property portfolio;•

~~seek to attract and retain skilled personnel;~~

•seek to attract and retain skilled personnel;•

~~create additional infrastructure to support our operations as a public company and our product development and planned future commercialization efforts; and~~

•

create additional infrastructure to support our operations as a public company and our product development and planned future commercialization efforts; and experience any delays or encounter issues with the development and potential for regulatory approval of our clinical candidates such as safety issues, clinical trial accrual delays, longer follow-up for planned studies, additional major studies, or supportive studies necessary to support marketing approval.

Further, the net losses we incur may fluctuate significantly from quarter to quarter and year to year, such that a period-to-period comparison of our results of operations may not be a representative indication of our future performance.

Prior to 2021, we never generated any product revenue and may never be profitable.

We have one product approved for commercialization in the U.S. and EU for two ultra-rare diseases. Zokinvy works to (i) reduce the risk of mortality in ~~Progeria,~~HGPS, and ~~for treatment of~~(ii) treat processing-deficient progeroid laminopathies with either heterozygous LMNA mutation with progerin-like protein accumulation, or homozygous or compound heterozygous ZMPSTE24 ~~mutations,~~mutations. Zokinvy was approved by the FDA in November 2020 and launched commercially in the U.S. in January 2021. In July 2022, our MAA for Zokinvy was approved by the EC, under the exceptional circumstances procedure. The Marketing Authorization (MA) is subject to the EMA’s continued review on an annual basis of new efficacy and safety information which may become available. Our ability to generate substantial revenue and achieve profitability depends on our ability ~~alone or with strategic collaboration partners,~~ to (i) obtain the regulatory and marketing approvals necessary to commercialize Zokinvy in foreign jurisdictions, alone or with strategic collaboration partners, and (ii) to successfully complete the development of, and obtain the regulatory and marketing approvals necessary to commercialize, more of our product candidates in the U.S. or foreign jurisdictions. We do not anticipate generating significant product revenue for the foreseeable future. Our ability to generate future product revenue depends heavily on our success in many areas, including, but not limited to:

•	~~completing research and development of our product candidates;~~

•	~~obtaining additional and maintaining current regulatory and marketing approvals for~~•completing research and development of our product candidates;

•obtaining additional and maintaining current regulatory and marketing approvals for our product candidates;•

manufacturing product candidates and establishing and maintaining supply and manufacturing relationships with third parties that meet regulatory requirements and our supply needs in sufficient quantities to meet market demand for our product candidates, if approved;

•manufacturing product candidates and establishing and maintaining supply and manufacturing relationships with third parties that meet regulatory requirements and our supply needs in sufficient quantities to meet market demand for our product candidates, if approved;•

~~marketing, launching and commercializing product candidates for which we obtain regulatory and marketing approval, either directly or with a collaborator or distributor;~~

•marketing, launching and commercializing product candidates for which we obtain regulatory and marketing approval, either directly or with a collaborator or distributor;•

~~gaining market acceptance of our product candidates as treatment options;~~

•gaining market acceptance of our product candidates as treatment options;•

~~addressing any competing products;~~

•addressing any competing products;•

~~protecting and enforcing our intellectual property rights, including patents, trade secrets, and know-how;~~

•protecting and enforcing our intellectual property rights, including patents, trade secrets, and know-how;•

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

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

~~obtaining reimbursement or pricing for our product candidates that supports profitability; and~~

•obtaining reimbursement or pricing for our product candidates that supports profitability; and•

~~attracting, hiring, and retaining qualified personnel.~~

•attracting, hiring, and retaining qualified personnel.

Even if we obtain additional product approvals for commercial sale, we anticipate incurring significant costs associated with commercializing any approved product candidate. Our current pipeline of product candidates has been in-licensed from third parties and we will have to develop or acquire manufacturing capabilities in order to continue development and potential commercialization of our product candidates. Additionally, if we are not able to generate sufficient revenue from the sale of any approved products, we may never become profitable.

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

To the extent that we raise additional capital through the sale of equity, including pursuant to the 2022 ATM Facility, debt or other securities convertible into equity, ~~your~~stockholder ownership interest will be diluted, and the terms of these new securities may include liquidation or other preferences that adversely affect your rights as a common stockholder such as the Loan and Security Agreement we entered into with ~~Oxford Finance LLC (Oxford Finance)~~Innovatus Life Sciences Lending Fund I, LP (Innovatus) in ~~December 2016~~June 2022 (the ~~Oxford~~Innovatus Loan). The ~~Oxford~~Innovatus Loan was a ~~$25.0~~$75.0 million debt financing arrangement with ~~Oxford Finance~~Innovatus wherein we borrowed the first tranche of ~~$15.0~~$40.0 million upon closing of the debt financing in December 2016. In May 2018, we entered into an amendment to the Oxford Loan and borrowed $5.0 million. In August 2018, we drew the final $5.0 million upon achievement of certain clinical milestones. In March 2019, we entered into the third amendment to the Oxford Loan to refinance our outstanding principal balance of $23.3 million. Upon refinancing, the Oxford Loan was increased to $35.0 million in aggregate commitments, of which $30.0 million in principal is outstanding. On February 23, 2021, we entered into the fifth amendment to the Oxford Loan.June 2022. The ~~amendment extended the interest only period by 17 months until~~

September 1, 2022, followed by 19 equal monthly payments of principal and interest. On October 6, 2021, we entered into the sixth amendment to the Oxford Loan. As a result, the Amended Oxford Loan will bear interest at the LIBOR replacement rate which is the sum of the alternate benchmark rate and the LIBOR replacement spread. The OxfordInnovatus Loan is secured by perfected first priority liens on our ~~assets, excluding intellectual property but including a commitment by us to not allow any liens to be placed upon such intellectual property.~~assets. The ~~Oxford~~Innovatus Loan includes customary events of default, including failure to pay amounts due, breaches of covenants and warranties, material adverse effect events, certain cross defaults and judgments, and insolvency.

If we raise additional funds through collaborations, strategic alliances or licensing arrangements with third parties, we may have to relinquish valuable rights to our product candidates or future revenue streams or grant licenses on terms that are not favorable to us. Our ability to raise additional capital may be adversely impacted by worsening global economic conditions and continuing disruptions to and volatility in the credit and financial markets in the ~~United States~~U.S. and worldwide resulting from the ongoing COVID-19 pandemic. We cannot assure you that we will be able to obtain additional funding if and when necessary to fund our entire portfolio of product candidates to meet our projected plans. If we are unable to obtain funding

on a timely basis, we may be required to delay or discontinue one or more of our development programs or the commercialization of any product candidates or be unable to expand our operations or otherwise capitalize on potential business opportunities, which could materially affect our business, financial condition, and results of operations.

Covenants in the ~~Oxford~~Innovatus Loan restrict our business and operations in many ways, and if we do not effectively comply with our covenants, our financial conditions and results of operations could be adversely affected.

The ~~Oxford~~Innovatus Loan provides for up to ~~$35.0~~$75.0 million in term loans due on ~~March 1, 2024,~~August 31, 2027, of which ~~$30.0~~$40.0 million in principal is outstanding as of March 31, ~~2022.~~2023. All of our current and future assets, ~~except for intellectual property,~~ secure our borrowings under the ~~Oxford~~Innovatus Loan. The ~~Oxford~~Innovatus Loan requires that we comply with certain covenants applicable to us, including among other things, covenants restricting dispositions, changes in business, management, ownership or business locations, mergers or acquisitions, indebtedness, encumbrances, distributions, investments, transactions with affiliates and subordinated debt, any of which could restrict our business and operations, particularly our ability to respond to changes in our business or to take specified actions to take advantage of certain business opportunities that may be presented to us. Our failure to comply with any of the covenants could result in a default under the ~~Oxford~~Innovatus Loan, which could permit the lenders to declare all or part of any outstanding borrowings to be immediately due and payable. If we are unable to repay those amounts, the lenders under the ~~Oxford~~Innovatus Loan could proceed against the collateral granted to them to secure that debt, and our inability to use or dispose of those assets would seriously harm our business. In addition, should we be unable to comply with these covenants or if we default on any portion of our outstanding borrowings, the lenders can also impose a 5.0% penalty, restrict access to additional borrowings under the loan and security agreement, and accelerate the maturity of the debt. Any default under the ~~Oxford~~Innovatus Loan would materially affect our liquidity and ability to fund our operations and complete our planned clinical trials and regulatory filings would be substantially impaired.

~~If the London Inter-Bank Offered Rate, or LIBOR, is discontinued, interest payments under the Oxford Loan may be calculated using another reference rate.~~

In July 2017, the Chief Executive of the United Kingdom Financial Conduct Authority (FCA), which regulates LIBOR, announced that the FCA intended to phase out the use of LIBOR by the end of 2021. In addition, the FCA and certain U.S. regulators have stated that, despite expected publications of U.S. dollar LIBOR through June 30, 2023, no new contracts using U.S. dollar LIBOR should be entered into after December 31, 2021. In the United States, the U.S. Federal Reserve, in conjunction with the Alternative Reference Rates Committee, a steering committee comprised of large U.S. financial institutions, has recommended that U.S. dollar LIBOR be replaced by the Secured Overnight Financing Rate, or SOFR, a new index calculated by short-term repurchase agreements, backed by US Treasury securities. LIBOR is used as a benchmark rate throughout the Oxford Loan. On October 6, 2021, we entered into the sixth amendment to the Oxford Loan (the Sixth Amendment) to replace the LIBOR benchmark rate with the LIBOR replacement rate upon a LIBOR transition event, as discussed more fully in Note 8 to the unaudited condensed consolidated financial statements included within Part II, Item 8 of this Quarterly Report on Form 10-Q. While we do not currently expect the impact of this change to be material, there remains uncertainty regarding the future utilization of LIBOR and the nature of any replacement rate, including the LIBOR replacement rate under the Sixth Amendment, and any potential effects of the transition away from LIBOR on us are not fully known. The transition process may involve, among other things, increased volatility and illiquidity in markets for instruments that currently rely on LIBOR and may result in increased borrowing costs, the effectiveness of related transactions such as hedges, or uncertainty under applicable documentation, including the Oxford Loan. As a result, our ability to refinance our credit agreement or other indebtedness or to hedge our exposure to floating rate instruments may be impaired, which would adversely affect the operations of our business.

Risks Related to the Development of our Product Candidates

We are dependent on the success of our product candidates, which are in various stages of clinical development. Certain of our product candidates have produced results in academic settings to date or for other indications than those that we contemplate, and we cannot give any assurance that we will generate data for any of our product candidates sufficient to receive regulatory approval in our planned indications, which will be required before they can be commercialized.

To date, we have invested substantially all of our efforts and financial resources to identify, acquire, and develop our portfolio of product candidates. Our future success is dependent on our ability to further develop, obtain regulatory approvals for, and commercialize one or more of these product candidates. Our NDA for Zokinvy to reduce the risk of mortality in ~~Progeria,~~HGPS, and for treatment of processing-deficient progeroid laminopathies (PL) with either heterozygous LMNA mutation with progerin-like protein accumulation, or homozygous or compound heterozygous ZMPSTE24 mutations, was approved in November 2020. Our MAA is currently under standard review with the EMA and we have received feedback from the CHMP with respect to our pending MAA requesting additional information relating to the demonstration of efficacy for Zokinvy. While we are working closely with the CHMP to address this feedback, we cannot be certain of the timing or outcome of such interactions. In addition, if the EMA rejects our MAA or we decide to withdraw our application, we may no longer be eligible for temporary reimbursement in France for the use of Zokinvy under the Autorisation Temporaire d'Utilisation (ATU) program, which was granted for a term of one year. Prior to the U.S. Zokinvy commercial launch in 2021, we had not generated revenue from sales of any ~~drugs~~products and may never be able to develop or commercialize additional product candidates. In addition, we have a commitment to provide access to Zokinvy for patients with ~~Progeria~~HGPS and ~~processing-deficient progeroid laminopathies~~PL with either heterozygous LMNA mutation with progerin-like protein accumulation, or homozygous or compound heterozygous ZMPSTE24 mutations, for no or minimal cost to those patients.

With respect to potential commercial products, we currently have ~~three~~two product candidates that are in Phase 3 clinical development, ~~lonafarnib for HDV, lambda~~lonafarnib-based regimens for HDV and peginterferon lambda for ~~COVID-19 through an investigator sponsored study, and two development programs focused on two separate indications that we believe have completed Phase 2 and are advancing towards~~HDV. Phase 3 study startup activities for avexitide ~~for~~in HI ~~and PBH.~~have been initiated. It may be years before our studies are ~~initiated~~completed, and ~~completed,~~new studies are initiated, if at all.

We provide our geographically diverse clinical sites with good clinical practice protocols. We review and monitor the execution of our protocols at our various sites in an effort to understand those protocols are being followed. There can be no assurance that the data we develop for our product candidates in our planned indications will be sufficient or complete enough to obtain regulatory approval. Likewise, there can be no assurance that the data obtained from foreign clinical trial sites in studies not conducted under an investigational new drug application, or IND, will be accepted in support of an application for regulatory approval or authorization for ~~use.~~

usein the U.S. Similarly, data obtained from foreign clinical trial sites may not be accepted by other foreign regulatory authorities in support of an application for regulatory approval or authorization for use in these jurisdictions.

•We are not permitted to market or promote any of our product candidates before we receive regulatory approval from the FDA or comparable foreign regulatory authorities, and we may never receive such regulatory approval for any of our current product candidates. We cannot be certain that any of our product candidates will be successful in clinical studies or receive regulatory approval. Further, our product candidates may not receive•

We are not permitted to market or promote any of our product candidates before we receive regulatory approval from the FDA or comparable foreign regulatory authorities, and we may never receive such regulatory approval for any of our current product candidates. We cannot be certain that any of our product candidates will be successful in clinical studies or receive regulatory approval. Further, our product candidates may not receive regulatory approval even if they are successful in clinical studies. If we do not receive regulatory approvals for our product candidates, we may not be able to continue our operations.

regulatory approval even if they are successful in clinical studies. If we do not receive regulatory approvals for our product candidates, we may not be able to continue our operations.

We may not be able to obtain FDA approval of any future NDA or BLA for our product candidates.

The clinical development, manufacturing, labeling, packaging, storage, recordkeeping, advertising, promotion, export, import, marketing and distribution and other possible activities relating to ~~lonafarnib,~~lonafarnib-based regimens, peginterferon lambda, avexitide and any other product candidate that we may develop in the future are subject to extensive regulation in the United States. Prior to the approval of our NDA for Zokinvy to reduce the risk of mortality in ~~Progeria,~~HGPS, and for treatment of ~~processing-deficient progeroid laminopathies~~PL with either heterozygous LMNA mutation with progerin-like protein accumulation, or homozygous or compound heterozygous ZMPSTE24 mutations, we had not submitted an application for approval or obtained FDA approval for any product.

Approval of an NDA or a BLA is not guaranteed, and the approval process is an expensive and uncertain process that may take several years. The FDA and foreign regulatory entities also have substantial discretion in the approval process. The number and types of preclinical studies and clinical trials that will be required for approval varies depending on the product candidate, the disease or the condition that the product candidate is designed to target and the regulations applicable to any particular product candidate. Data are subject to varying interpretation and the FDA may not agree that our clinical data support that any of our product candidates are safe and effective for the proposed therapeutic use. Despite the time and expense associated with preclinical studies and clinical trials, failure can occur at any stage, and we could encounter problems that require us to repeat or perform additional preclinical studies or clinical trials or generate additional chemistry, manufacturing and controls data, including ~~drug~~ product stability data. In previous studies, ECG abnormalities were observed in our lonafarnib program. ~~We do not expect that this will impact the conduct of the D-LIVR HDV study.~~ The FDA and similar foreign authorities could delay, limit or deny approval of a product candidate, and may ultimately approve the product for narrower indications or with unfavorable labeling that would impede our commercialization of the ~~drug.~~

product.

Approval procedures vary among countries and can involve additional product testing and additional administrative review periods, including obtaining reimbursement and pricing approval in select markets. The time required to obtain approval in other countries might differ from that required to obtain FDA approval. The regulatory approval process in other countries may include all of the risks associated with FDA approval as well as additional, presently unanticipated, risks. Regulatory approval in one country does not ensure regulatory approval in another, but a failure or delay in obtaining regulatory approval in one country may negatively impact the regulatory process in others, including the risk that our product candidates may not be approved for all indications requested and that such approval may be subject to limitations on the indicated uses for which the product may be marketed.

Clinical development is expensive, time consuming and involves significant risk. We cannot guarantee that any clinical studies will be conducted as planned or completed on schedule, if at all. A failure of one or more clinical studies can occur at any stage of development. Events that may prevent successful or timely completion of clinical development include but are not limited to:

•	inability to generate satisfactory preclinical, toxicology, or other in vivo or in vitro data or diagnostics to support the initiation or continuation of clinical studies necessary for product approval;

•inability to generate satisfactory preclinical, toxicology, or other in vivo or in vitro data or diagnostics to support the initiation or continuation of clinical studies necessary for product approval;•

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

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

~~delays in obtaining required Institutional Review Board (IRB) approval at each clinical study site;~~

•	~~failure to permit the conduct of a study by regulatory authorities, after review of an investigational new drug (IND) or equivalent foreign application or amendment;~~

•delays in obtaining required Institutional Review Board (IRB) approval at each clinical study site;•

~~delays in recruiting qualified patients, or patients dropping out of, in our clinical studies, including as a result of the evolving COVID-19 global pandemic;~~

•failure to permit the conduct of a study by regulatory authorities, after review of an investigational new drug (IND) or equivalent foreign application or amendment;•

~~feasibility of continuous trial execution in countries impacted by war, geopolitical conflict and other humanitarian crises;~~

•delays in recruiting qualified patients, or patients dropping out of, in our clinical studies, including as a result of the evolving COVID-19 global pandemic;•

~~failure by clinical sites or our CROs or other third parties to adhere to clinical study requirements or report complete findings;~~

•feasibility of continuous trial execution in countries impacted by war, geopolitical conflict and other humanitarian crises;•

~~failure to perform the clinical studies in accordance with the FDA’s good clinical practice (GCP) requirements, or applicable foreign regulatory guidelines;~~

•failure by clinical sites or our CROs or other third parties to adhere to clinical study requirements or report complete findings;•

~~occurrence of adverse events associated with our product candidates;~~

•failure to perform the clinical studies in accordance with the FDA’s good clinical practice (GCP) requirements, or applicable foreign regulatory guidelines;•

~~changes in regulatory requirements and guidance that require amending or submitting new clinical protocols;~~

•	~~the cost of clinical studies~~•occurrence of adverse events associated with our product candidates;

•changes in regulatory requirements and guidance that require amending or submitting new clinical protocols;•

negative or inconclusive results from our clinical trials which may result in our deciding, or regulators requiring us, to conduct additional clinical studies or abandon development programs in other ongoing or planned indications for a product candidate; and

•the cost of clinical studies of our product candidates;•

~~delays in reaching agreement on acceptable terms with third-party manufacturers and the time for manufacture of sufficient quantities of our product candidates for use in clinical studies.~~

•negative or inconclusive results from our clinical trials which may result in our deciding, or regulators requiring us, to conduct additional clinical studies or abandon development programs in other ongoing or planned indications for a product candidate; and

•delays in reaching agreement on acceptable terms with third-party manufacturers and the time for manufacture of sufficient quantities of our product candidates for use in clinical studies.

Any inability to successfully complete clinical development and obtain regulatory approval could result in additional costs to us or impair our ability to generate revenue. Clinical study delays could also shorten any periods during which our products have patent protection and may allow competitors to develop and bring products to market before we do, which could impair our ability to obtain or maintain Orphan Drug designation exclusivity and to successfully commercialize our product candidates and may harm our business and results of operations.

~~We may~~

Given we are not be able to receive an Emergency Use Authorization (EUA) from FDA ~~for~~in the U.S., we may not be able to receive a similar temporary use ~~of lambda in COVID-19, and, even if~~authorization from foreign regulatory agencies. If we do receive an EUA or similar temporary use authorization, absent ~~supplemental NDA or BLA approval~~a full marketing authorization for that indication, ~~such EUA~~our ability to sell our products would be revoked when the COVID-19 ~~emergency terminates.~~

Section 564 of the FDCA allows the FDA to authorize the shipment of drugs, biological products, or medical devices that either lack required approval, licensure, or clearance (unapproved products), or are approved but are to be used for unapproved ways to diagnose, treat, or prevent serious diseases or conditions in the event of an emergency declaration by the HHS Secretary.

~~On February 4, 2020, then-HHS Secretary Alex M. Azar II declared a~~ public health emergency for COVID-19, under 21 U.S.C. § 360bbb-3(b)(1), justifying the authorization of emergency use of unapproved therapeutic products, or unapproved uses of approved or cleared therapeutic products, to treat COVID-19. This determination was published in the Federal Register on February 7, 2020.

~~While this emergency declaration is effective, the~~terminates.

On October 5, 2022, we announced that, following feedback from FDA, ~~may authorize the use of an unapproved product or an unapproved use of an approved product if it concludes that:~~

•~~an agent referred to in the emergency declaration could cause a serious or life-threatening disease or~~ ~~condition;~~

•it is reasonable to believe that the authorized product may be effective in diagnosing, treating, or preventing that disease or condition or a serious or life-threatening disease or condition caused by an approved ~~product or a product marketed under an EUA;~~

•the known and potential benefits of the authorized product, when used for that disease or condition, outweigh known and potential risks, taking into consideration the material threat of agents identified in the emergency ~~declaration;~~

•~~there is no adequate, approved, and available alternative to the authorized product for diagnosing, preventing, or treating the relevant disease or~~ ~~condition;~~

•~~any other criteria prescribed by the FDA is satisfied.~~

~~Medical products that are granted~~we will not submit an EUA are only permitted to commercialize their products under the terms and conditions provided in the authorization. The FDCA authorizes FDA to impose such conditions on an EUA as may be necessary to protect the public health. Consequently, postmarketing requirements will vary across EUAs. In addition, FDA has, on occasion, waived requirementsapplication for ~~drugs marketed under an EUA.~~

Generally, EUAs for unapproved products or unapproved uses of approved products require that manufacturers distribute factsheets for healthcare providers, addressing significant known and potential benefits and risk, and the extent to which benefits and risks are unknown, and the fact that FDA has authorized emergency use; and, distribution of factsheets for recipients of the product, addressing significant known and potential benefits and risk, and the extent to which benefits and risks are unknown, the option to accept or refuse the product, the consequences of refusing, available alternatives and the fact that FDA has authorized emergency use.

Generally, EUAs for unapproved products and, per FDA’s discretion, EUAs for unapproved uses of approved products, include requirements for adverse event monitoring and reporting, and other recordkeeping and reporting requirements. Note, however, that approved products are already subject to equivalent requirements.

In addition, the FDA may include various requirements in an EUA as a matter of discretion as deemed necessary to protect the public health, including restrictions on which entities may distribute the product, and how to perform distribution (including requiring that distribution be limited to government entities), restrictions on who may administer the product, requirements for collection and analysis of safety and effectiveness data, waivers of cGMP, and restrictions applicable to prescription drugs or restricted devices (including advertising and promotion restrictions).

~~The FDA may revoke an EUA when it is determined that the underlying health emergency no longer exists or warrants such authorization, if the conditions~~peginterferon lambda for the ~~issuance~~treatment of ~~the EUA are no longer met, or if other circumstances make revocation appropriate~~patients with mild-to-moderate COVID-19. If we decide to ~~protect the public health or safety. We cannot predict how long, if ever,~~submit a future application for an EUA, ~~would remain in place.~~

~~We cannot predict with certainty whether we can support an application to receive an EUA. Even if we do submit an application,~~ we cannot predict whether FDA will grant an ~~EUA for the use of lambda in COVID-19.~~EUA. If we do not receive an EUA from FDA, we will not be able to commercialize ~~lambda in COVID-19~~ future products and may be required to conduct additional clinical trials for an EUA. Obtaining such an authorization is dependent upon a number of factors, which are not under our ~~control. For example, the TOGETHER study an investigator sponsored study conducted within a single country, Brazil. FDA may require a company-sponsored study with data from additional patient populations.~~control. Even if an EUA is received, we also cannot predict how long, if ever, an EUA would remain in place.

We do intend to pursue similar temporary use authorizations in non-U.S. jurisdictions.

Various regulatory pathways are available in jurisdictions outside the United States to make products available for emergency use. For example, regulatory authorities in certain EU Member States may temporarily authorize the distribution of an unauthorized drug in response to the suspected or confirmed spread of pathogenic agents such as the virus which is causing COVID-19. Obtaining such a temporary authorization is dependent upon a number of factors, which are not under our control. If such authorizations would be granted, they would only apply for a limited period of time. We might thus no longer be authorized to distribute our product under these authorizations if that time limit expired or the pandemic terminates.

The regulatory authorities in the EU or in other jurisdictions outside the U.S. may grant a conditional marketing authorization for medicinal products intended for the treatment of seriously debilitating or life-threatening diseases prior to the submission of comprehensive clinical data if that treatment is of major therapeutic advantage to the patients concerned or no other authorized treatment is available. In emergency situations, such a conditional marketing authorization may also be granted for these medicinal products where comprehensive preclinical or pharmaceutical data have not been supplied.

These conditional marketing authorizations are subject to specific conditions (e.g., completing on-going studies or conducting new studies) which must be fulfilled within a timeline specified in the marketing authorization. These marketing authorizations are valid for a short period of time (e.g., one year) which can usually be renewed. If we would apply for such a conditional marketing authorization the regulatory authority concerned may reject our application because it considers that the benefit-risk balance of our product is not favorable or it judges it unlikely that we would be able to provide comprehensive data. If we would obtain such a conditional marketing authorization we may not be able to complete (timely) the studies which the regulatory authority imposed as a condition for the marketing authorization or the data collected in the course of these studies may indicate that our product does not have a favorable benefit-risk profile. As a result, we may not be able to continue distributing our product because the conditional marketing authorization has been revoked or not renewed, or the regulatory authority refused finally to grant a regular marketing authorization.

Regulatory authorities in the EU or other jurisdictions outside the EU may make a product available for compassionate reasons to a group of patients with a chronically or seriously debilitating disease or whose disease is considered to be life-threatening, and who cannot be treated satisfactorily with an authorized medicinal product provided that the product is subject of an application for marketing authorization or is undergoing clinical trials. If we would request a regulatory authority to make our product available to patient under these conditions the regulatory authority may reject our request if, for example, it considers that the patients concerned can be treated satisfactorily with other products that are already authorized.

Programs which make products available under the conditions mentioned above are usually authorized for a limited period of time (e.g., one year). Regulatory authorities may not renew expiring authorizations for these programs if we terminate prematurely a clinical trial with our product or decide not to submit or to withdraw an application for marketing authorization in the jurisdiction concerned. That may, for example, happen because pharmacovigilance data or other data collected during our clinical trials indicate that our product does not have the appropriate benefit-risk balance.

Our product candidates may cause undesirable side effects or have other properties that could delay or prevent their regulatory approval, limit the commercial profile of an approved label, or result in significant negative consequences following marketing approval, if any.

Our lonafarnib product candidate has been studied in thousands of oncology patients, and the most common non-hematologic adverse events of any grade were gastrointestinal system disorders (nausea, anorexia, diarrhea and vomiting), weight loss, fatigue and rash. Use of Zokinvy to reduce the risk of mortality in ~~Progeria,~~HGPS, and for treatment of processing-deficient progeroid laminopathies with either heterozygous LMNA mutation with progerin-like protein accumulation, or homozygous or compound heterozygous ZMPSTE24 mutations, has been reported to cause ECG abnormalities, but these ECG abnormalities have not resulted in a risk of mortality for these patients. There is no guarantee that additional or more severe side effects or other properties will not be identified through ongoing clinical studies by other uses of lonafarnib for other indications or our own clinical trials. Our peginterferon lambda product candidate is well-characterized and has been studied in thousands of HBV and HCV patients, and the most common adverse events seen are moderate headache, pyrexia, fatigue, and myalgia. ALT flares that were seen result from vigorous antiviral immunological response to treatment, not due to direct hepatotoxicity. There is no guarantee that additional or more severe side effects will not be identified through ongoing clinical studies for other uses of peginterferon lambda. Undesirable side effects, other properties, and negative results for other indications may negatively impact the development and potential for approval of our product candidates for our proposed indications. For example, the ECG abnormalities seen with lonafarnib in HGPS and PL patients has the potential to impact the labeling for ~~lonafarnib combined with ritonavir~~lonafarnib-based regimens for HDV.Our avexitide product candidate has been studied in 39 HI patients and 54over 70 PBH patients, and the most common adverse events are injection site ~~bruising,~~bruising/reaction, nausea, and headache. There is no guarantee that additional or more severe side effects will not be identified through ongoing clinical studies for other uses of avexitide in clinical trials.

Additionally, even if one or more of our current product candidates receives marketing approval, and we or others later may identify undesirable side effects caused by such products, potentially significant negative consequences could result, including but not limited to:

•	~~regulatory authorities may withdraw approvals of such products;~~

•regulatory authorities may withdraw approvals of such products;•

~~regulatory authorities may require additional warnings on the label;~~

•regulatory authorities may require additional warnings on the label;•

we may be required to create a Risk Evaluation and Mitigation Strategy (REMS) plan, which could include a medication guide outlining the risks of such side effects for distribution to patients, a communication plan for healthcare providers, and/or other elements to assure safe use;

•we may be required to create a Risk Evaluation and Mitigation Strategy (REMS) plan, which could include a medication guide outlining the risks of such side effects for distribution to patients, a communication plan for healthcare providers, and/or other elements to assure safe use;•

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

•	~~our reputation may suffer.~~

Manufacturers and manufacturers’ facilities are required to continuously comply with FDA and comparable foreign regulatory authority requirements, including ensuring that quality control and manufacturing procedures conform to current Good Manufacturing Practices (cGMP) regulations and corresponding foreign regulatory manufacturing requirements. As such, we and our contract manufacturers will be subject to continual review and inspections to assess compliance with cGMP and adherence to commitments made in any NDA, BLA, or MAA.

In addition, our reliance on third-party manufacturers exposes us to the following additional risks:

•	~~We may be unable to identify manufacturers on acceptable terms or at all;~~

•We may be unable to identify manufacturers on acceptable terms or at all;•

~~Our third-party manufacturers might be unable to timely formulate and manufacture our product or produce the quantity and quality required to meet our clinical and commercial needs, if any;~~

•Our third-party manufacturers might be unable to timely formulate and manufacture our product or produce the quantity and quality required to meet our clinical and commercial needs, if any;•

~~Contract manufacturers may not be able to execute our manufacturing procedures appropriately;~~

•Contract manufacturers may not be able to execute our manufacturing procedures appropriately;•

Our future contract manufacturers may not perform as agreed or may not remain in the contract manufacturing business for the time required to supply our clinical trials or to successfully produce, store and distribute our products;

•Our future contract manufacturers may not perform as agreed or may not remain in the contract manufacturing business for the time required to supply our clinical trials or to successfully produce, store and distribute our products;•

Manufacturers are subject to ongoing periodic unannounced inspection by the FDA and corresponding state agencies to ensure strict compliance with cGMP and other government regulations and corresponding foreign standards. We do not have control over third-party manufacturers’ compliance with these regulations and standards;

•Manufacturers are subject to ongoing periodic unannounced inspection by the FDA and corresponding state agencies to ensure strict compliance with cGMP and other government regulations and corresponding foreign standards. We do not have control over third-party manufacturers’ compliance with these regulations and standards;•

~~We may not own, or may have to share, the intellectual property rights to any improvements made by our third-party manufacturers in the manufacturing process for our product candidates; and~~

•We may not own, or may have to share, the intellectual property rights to any improvements made by our third-party manufacturers in the manufacturing process for our product candidates; and•

~~Our third-party manufacturers could breach or terminate their agreement with us.~~

•Our third-party manufacturers could breach or terminate their agreement with us.

Each of these risks could delay our clinical trials, the approval of any of our product candidates by the FDA or comparable foreign regulatory authorities or the commercialization of our product candidates or result in higher costs or deprive us of potential product revenue. In addition, we rely on third parties to perform release testing on our product candidates prior to delivery to patients. If these tests are not conducted appropriately and test data is not reliable, patients could be put at risk of serious harm and could result in product liability suits.

The manufacturing of medical products is complex and requires significant expertise and capital investment, including the development of advanced manufacturing techniques and process controls. Manufacturers of biologic products often

encounter difficulties in production, particularly in scaling up and validating initial production and absence of contamination. These problems include difficulties with production costs and yields, quality control, including stability of the product, quality assurance testing, operator error, shortages of qualified personnel, as well as compliance with strictly enforced federal, state and foreign regulations. Furthermore, if contaminants are discovered in our supply of our product candidates or in the manufacturing facilities, such manufacturing facilities may need to be closed for an extended period of time to investigate and remedy the contamination. We cannot assure you that any stability or other issues relating to the manufacture of our product candidates will not occur in the future. Additionally, our manufacturers may experience manufacturing difficulties due to resource constraints or as a result of labor disputes or unstable political environments. If our manufacturers were to encounter any of these difficulties, or otherwise fail to comply with their contractual obligations, our ability to provide our product candidates to patients in clinical trials would be jeopardized. Any delay or interruption in the supply of clinical trial supplies could delay the completion of clinical trials, increase the costs associated with maintaining clinical trial programs and, depending upon the period of delay, require us to commence new clinical trials at additional expense or terminate clinical trials completely.

If the market opportunities for our product candidates are smaller than we believe they are, we may not meet our revenue expectations and, even assuming approval of a product candidate, our business may suffer. Because the patient populations in the market for our product candidates may be small, we must be able to successfully identify patients and acquire a significant market share to achieve profitability and growth.

We focus our product development principally on treatments for rare and ultra-rare diseases. Given the small number of patients who have the diseases that we are targeting, our eligible patient population and pricing estimates may differ significantly from the actual market addressable by our product candidate. Our projections of both the number of people who have these diseases, as well as the subset of people with these diseases who have the potential to benefit from treatment with our product candidates, are based on our beliefs and estimates. These estimates have been derived from a variety of sources, including the scientific literature, patient foundations, or market research, and may prove to be incorrect. Further, new studies may change the estimated incidence or prevalence of these diseases. The number of patients may turn out to be lower than expected. For example, ~~for lonafarnib~~although we believe that our lonafarnib-based regimens and peginterferon lambda ~~HDV is associated with hepatitis B virus infection, which is a pre-requisite for the replication of HDV. Although we believe that the~~ data are supportive of antiviral activity against HDV, there can be no assurance that our clinical trials will successfully address this condition. Likewise, the potentially addressable patient population for each of our product candidates may be limited or may not be amenable to treatment with our product candidates, and new patients may become increasingly difficult

to identify or gain access to, which would adversely affect our results of operations and our business. Moreover, we expect that the sales of Zokinvy to patients with ~~Progeria, or processing-deficient progeroid laminopathies with either heterozygous LMNA mutation with progerin-like protein accumulation, or homozygous or compound heterozygous ZMPSTE24 mutations,~~progeria will have limited profits given the ultra-rare nature of these diseases.

We face intense competition and rapid technological change and the possibility that our competitors may develop therapies that are similar, more advanced, or more effective than ours, which may adversely affect our financial condition and our ability to successfully commercialize our product candidates.

The biotechnology and pharmaceutical industries are intensely competitive and subject to rapid and significant technological change. We are currently aware of various existing therapies that may compete with our product candidates. For example, we have competitors both in the United States and internationally, including multinational pharmaceutical companies, specialty pharmaceutical companies and biotechnology companies. Some of the pharmaceutical and biotechnology companies we expect to compete with include Gilead Sciences, ~~Merck, Roche, Holding, Actelion~~Vir Biotechnology, Janssen Pharmaceuticals, ~~US, Johnson & Johnson,~~ Replicor, ~~Arrowhead Pharmaceuticals, Novartis International,~~ Zealand Pharmaceuticals, Xeris Pharmaceuticals, Rezolute, Hanmi Pharmaceutical, and Crinetics Pharmaceuticals as well as other smaller companies or biotechnology startups and large multinational pharmaceutical companies. Many of our competitors have substantially greater financial, technical, and other resources, such as larger research and development staff and experienced marketing and manufacturing organizations. Additional mergers and acquisitions in the biotechnology and pharmaceutical industries may result in even more resources being concentrated in our competitors. As a result, these companies may obtain regulatory approval more rapidly than we are able to and may be more effective in selling and marketing their products as well. Smaller or early-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large, established companies. Competition may increase further as a result of advances in the commercial applicability of technologies and greater availability of capital for investment in these industries. Our competitors may succeed in developing, acquiring, or licensing on an exclusive basis, products that are more effective or less costly than any product candidate that we may develop, or achieve earlier patent protection, regulatory approval, product commercialization, and market penetration than we do. Additionally, technologies developed by our competitors may render our potential product candidates uneconomical or obsolete, and we may not be successful in marketing our product candidates against competitors.

Although we commercially launched Zokinvy following its FDA approval, we have limited marketing and sales experience. If we are unable to establish sales and marketing capabilities or enter into agreements with third parties to market and sell our product candidates, we may be unable to generate any revenue.

Although certain of our employees may have marketed, launched and sold other pharmaceutical products in the past while employed at other companies, we have limited recent experience selling and marketing our product candidates and we currently have a small sales and marketing organization. To successfully commercialize Zokinvy and additional products that may result from our development programs, we will need to invest in and expand these capabilities, either on our own or with others, which would be expensive, difficult and time consuming. Any failure or delay in the timely development of our internal commercialization capabilities could adversely impact the potential for success of our products.

Further, given our recent, limited experience in marketing and selling biopharmaceutical products, we may rely on future collaborators to commercialize our products. If collaborators do not commit sufficient resources to commercialize our future products and we are unable to develop the necessary marketing and sales capabilities on our own, we will be unable to generate sufficient product revenue to sustain or grow our business. We may be competing with companies that currently have extensive and well-funded marketing and sales operations, in particular in the markets our product candidates are intended to address. Without appropriate capabilities, whether directly or through third-party collaborators, we may be unable to compete successfully against these more established companies. In addition, we have established an expanded access program in order to make Zokinvy available for patients with ~~Progeria and processing-deficient progeroid laminopathies,~~progeria, which requires additional resources and costs to support.

The commercial success of any of our current or future product candidates will depend upon the degree of market acceptance by physicians, patients, third-party payors, and others in the medical community.

Even with the approvals from the FDA and comparable foreign regulatory authorities, the commercial success of our products will depend in part on the health care providers, patients, and third-party payors accepting our product candidates as medically useful, cost-effective, and safe. Any product that we bring to the market may not gain market acceptance by physicians, patients, third-party payors and other health care providers. The degree of market acceptance of any of our products will depend on a number of factors, including without limitation:

•	~~the timing of our receipt of any marketing and commercialization licensures;~~

•the timing of our receipt of any marketing and commercialization licensures;•

~~the terms of any licensures and the countries in which licensures are obtained;~~

•the terms of any licensures and the countries in which licensures are obtained;•

~~the efficacy of the product as demonstrated in clinical studies and potential advantages over competing treatments;~~

•the safety, efficacy, purity and/or potency of the product as demonstrated in clinical studies and potential advantages over competing treatments;•

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

•the prevalence and severity of the disease and any side effects;•

~~the clinical indications for which approval is granted, including any limitations or warnings contained in a product’s approved labeling;~~

•the clinical indications for which approval is granted, including any limitations or warnings contained in a product’s approved labeling;•

~~the convenience and ease of administration;~~

•the convenience and ease of administration;•

~~the cost of treatment;~~

•the cost of treatment;•

~~the willingness of the patients and physicians to accept these therapies or any new methods of administration;~~

•the willingness of the patients and physicians to accept these therapies or any new methods of administration;•

~~the marketing, sales and distribution support for the product;~~

•the marketing, sales and distribution support for the product;•

~~the publicity concerning our products or competing products and treatments;~~

•the publicity concerning our products or competing products and treatments;•

~~the success of our physician education programs;~~

•the success of our physician education programs;•

~~availability of alternative effective treatments for the disease indications our product candidates are intended to treat and the relative risks, benefits and costs of those treatments; and~~

•availability of alternative effective treatments for the disease indications our product candidates are intended to treat and the relative risks, benefits and costs of those treatments; and•

~~the pricing and availability of third-party insurance coverage and reimbursement.~~

•the pricing and availability of third-party insurance coverage and reimbursement.

Even if a product displays a favorable safety, efficacy, ~~and safety~~purity and/or potency profile upon approval, market acceptance of the product remains uncertain. Efforts to educate the medical community and third-party payors on the benefits of the products may require significant investment and resources and may never be successful. If our products fail to achieve an adequate level of acceptance by physicians, patients, third-party payors, and other health care providers, we will not be able to generate sufficient revenue to become or remain profitable.

Failure to obtain or maintain adequate reimbursement or insurance coverage for new or current products could limit our ability to market those products and decrease our ability to generate revenue.

We cannot be sure that reimbursement will be available for our products and, if coverage and reimbursement are available, what the level of reimbursement will be. Coverage may also be more limited than the indications for which the product is approved by the FDA or comparable foreign regulatory authorities. Reimbursement may impact the demand for, or the price of, our products.

The pricing, coverage and reimbursement of our products must be sufficient to support our commercial efforts and other development programs and the availability and adequacy of coverage and reimbursement by governmental and private payors are essential for most patients to be able to afford expensive treatments, particularly in Orphan Drug designated indications where the eligible patient population is small. Sales of our products will depend substantially, both domestically and abroad, on the extent to which the costs of our product candidates will be paid for or reimbursed by health maintenance, managed care, pharmacy benefit and similar healthcare management organizations, or government authorities, private health insurers, and other third-party payors. If coverage and reimbursement are not available, or are available only in limited amounts, we may have to subsidize or provide products for free or we may not be able to successfully commercialize our products. For example, Zokinvy for patients with ~~Progeria~~HGPS and processing-deficient progeroid laminopathies provided under an expanded access program may not result in reimbursement.

In addition, there is significant uncertainty related to the insurance coverage and reimbursement for newly approved products. In the United States, the principal decisions about coverage and reimbursement for new drugs are typically made by the Centers for Medicare & Medicaid Services (CMS), an agency within the U.S. Department of Health and Human Services (HHS), as CMS decides whether and to what extent a new drug will be covered and reimbursed under Medicare. Private payors ~~tend to~~often follow the coverage reimbursement policies established by CMS to a substantial degree. It is difficult to predict what CMS and other payors will decide with respect to ~~reimbursement~~coverage for products such as ours and what reimbursement ~~codes~~ our products may receive.

The process for determining whether a third-party payor will provide coverage for a drug product typically is separate from the process for setting the price of a drug product or for establishing the reimbursement rate that the payor will pay for the drug product once coverage is approved. Third-party payors may limit coverage to specific drug products on an approved list, also known as a formulary, which might not include all of the FDA-approved drugs for a particular indication. A decision by a third-party payor not to cover Zokinvy or any of our product candidates once approved could reduce ~~physician~~ utilization of such products and have a material adverse effect on our sales, results of operations and financial condition. Moreover, a third-party payor’s decision to provide coverage for a drug product does not imply that an adequate reimbursement ~~rate~~ will be ~~approved.~~available. Adequate third-party payor reimbursement may not be available to enable us to maintain price levels sufficient to realize an appropriate return on our investment in product development. Additionally, coverage and reimbursement for drug products can differ significantly from payor to payor. One third-party payor’s decision to cover a particular medical product or service does not ensure that other payors will also provide coverage for the medical product or service or will provide coverage at an adequate reimbursement rate. As a result, the coverage determination process will require us to provide scientific and clinical support for the use of our products to each payor separately and will be a time-consuming process.

Third-party payors are increasingly challenging the prices charged for medical products and services, examining the medical necessity and reviewing the cost-effectiveness of drug products and medical services, in addition to questioning safety and efficacy. If ~~these~~ third-party payors do not consider our products to be cost-effective compared to other available therapies, they may not cover our products after FDA approval or, if they do, the level of payment may not be sufficient to allow us to sell our products at a profit. Additionally, coverage policies and third‑party reimbursement rates may change at any time. Therefore, even if favorable coverage and reimbursement status is attained for one or more of our products, less favorable coverage policies and reimbursement rates may be implemented in the future. If we are unable to obtain and maintain sufficient third‑party coverage and adequate reimbursement, the commercial success of our products may be greatly hindered and our financial condition and results of operations may be materially and adversely affected.

Outside the United States, international operations are generally subject to extensive governmental price controls and other price-restrictive regulations, and we believe the increasing emphasis on cost-containment initiatives in Europe, Canada, and other countries has and will continue to put pressure on the pricing and usage of products. In many countries, the prices of products are subject to varying price control mechanisms as part of national health systems. Price controls or other changes in pricing regulation could restrict the amount that we are able to charge for our products. Accordingly, in markets outside the United States, the potential revenue may be insufficient to generate commercially reasonable revenue and profits.

Moreover, increasing efforts by governmental and third-party payors in the United States and abroad to limit or reduce healthcare costs may result in restrictions on coverage and the level of reimbursement for new products and, as a result, ~~they may not cover~~inadequate coverage or ~~provide adequate~~ payment for our products.

In the EU, coverage and reimbursement status of our products, if approved, are provided for by the national laws of the EU Member States. In the EU, pricing and reimbursement schemes vary widely from Member State to Member State. Some Member States provide that products can only be effectively marketed after a reimbursement price has been agreed. Some Member States may require the completion of additional studies in order to compare the cost-effectiveness of a particular drug candidate to currently available therapies (so called health technology assessment, or HTA) in order to obtain reimbursement or pricing approval. EU Member States may approve a specific price for a product or it may instead adopt a system of direct or indirect controls on the profitability of the Company placing the product on the market. Other Member States may allow companies to fix their own prices for products, but monitor and control prescription volumes and issue guidance to physicians to limit prescriptions. Recently, many countries in the EU have increased the amount of discounts required on pharmaceuticals and these efforts could continue as countries attempt to manage healthcare expenditures, especially in light of the severe fiscal and debt crises experienced by many countries in the EU. The downward pressure on healthcare costs in general, particularly prescription drugs, has become intense. As a result, increasingly high barriers are being erected to the entry of new products. Political, economic and regulatory developments may further complicate pricing negotiations, and pricing negotiations may continue after reimbursement has been obtained. Reference pricing used by various EU Member States, and parallel trade (arbitrage between low-priced and high-priced Member States), can further reduce prices. There can be no assurance that any country that has price controls or reimbursement limitations for drug products will allow favorable reimbursement and pricing arrangements for any of our products, if approved in those countries.

We expect to experience pricing pressures in connection with products due to ~~the increasing trend toward managed~~increased and continued efforts to limit or reduce healthcare ~~including the increasing influence of health maintenance organizations and additional legislative changes.~~spending. The downward pressure on healthcare costs in general, particularly prescription drugs, has and is expected to continue to increase in the future. As a result, profitability of our products may be more difficult to achieve even if they receive regulatory approval.

We intend to rely on a combination of exclusivity from Orphan Drug designation as well as patent rights for our product candidates and any future product candidates. If we are unable to obtain or maintain exclusivity from the combination of these approaches, we may not be able to compete effectively in our markets.

Our business strategy is to focus on product candidates for which Orphan Drug designation may be obtained in the major markets of the world. In addition, we rely or will rely upon a combination of patents, trade secret protection, and confidentiality agreements to protect the intellectual property related to our technologies and product candidates. ~~For example, the portfolio of patents licensed from Merck expires before the anticipated launch date of lonafarnib.~~ Our success depends in large part on our and our licensors’ ability to obtain regulatory exclusivity and maintain patent and other intellectual property protection in the United States and in other countries with respect to our proprietary technology and products.

Under the Orphan Drug Act, the FDA may designate a product as an Orphan Drug if it is intended to treat a rare disease or condition, defined as a patient population of fewer than 200,000 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~~product will be recovered from sales in the United States. In the European Union (the EU), the EMA’s Committee for Orphan Medicinal Products (COMP) 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 five in 10,000 persons in the EU. Additionally, designation is granted for products intended for the diagnosis, prevention, or treatment of a life-threatening, seriously debilitating or serious and chronic condition when, without incentives, it is unlikely that sales of the drug in the EU would be sufficient to justify the necessary investment in developing the drug or biological product or where there is no satisfactory method of diagnosis, prevention, or treatment, or, if such a method exists, the medicine must be of significant benefit to those affected by the condition.

In the United States, Orphan Drug designation entitles a party to financial incentives such as opportunities for grant funding towards clinical trial costs, tax advantages, and user-fee waivers. In addition, if a product receives the first FDA approval for the indication for which it has Orphan Drug designation, the product is entitled to Orphan Drug exclusivity, which means the FDA may not approve any other application to market the same ~~drug~~product for the same indication for a period of seven years, except in limited circumstances, such as a showing of clinical superiority over the product with orphan exclusivity or where the manufacturer is unable to assure sufficient product quantity.

Congress is considering updates to the Orphan Drug provisions of the FDCA in response to a recent decision by the U.S. Court of Appeals for the 11th Circuit. Any changes to the Orphan Drug provisions could change our opportunities for, or likelihood of success in obtaining, Orphan Drug exclusivity and would materially adversely affect our business, financial condition, results of operations, cash flows and prospects.

In the EU, Orphan Drug designation entitles a party to financial incentives such as reduction of fees or fee waivers and ten years of market exclusivity following drug or biological product approval. This period may be reduced to six years if the Orphan Drug designation criteria are no longer met, including where it is shown that the product is sufficiently profitable not to justify maintenance of market exclusivity.

Because the extent and scope of patent protection for our products may in some cases be limited, Orphan Drug designation is especially important for our products for which Orphan Drug designation may be available. For eligible ~~drugs,~~products, we plan to rely on the exclusivity period under the Orphan Drug Act to maintain a competitive position. If we do not obtain or maintain Orphan Drug exclusivity for our drug ~~products~~ and ~~biologic~~biological products that do not have broad patent protection, our competitors may then sell the same drug to treat the same condition sooner than if we had obtained Orphan Drug exclusivity and our revenue will be reduced.

Patent term extensions under the Hatch-Waxman Act in the United States and under supplementary protection certificates in ~~Europe~~the EU may be available to extend the patent or data exclusivity terms of products. With respect to ~~lonafarnib,~~lonafarnib-based regimens, peginterferon lambda and avexitide, a substantial portion of the potential commercial opportunity will likely rely on patent term extensions, and we cannot provide any assurances that any such patent term extensions will be obtained and, if so, for how long. As a result, we may not be able to maintain exclusivity for our products for an extended period after regulatory approval, which would negatively impact our business and results of operations. If we do not have sufficient patent terms or regulatory exclusivity to protect our products, our business and results of operations will be adversely affected.

Third parties may assert that we are using or exploiting their proprietary technology without authorization. There may be third-party patents or patent applications with claims to materials, formulations, methods of manufacture, or methods for treatment related to the use or manufacture of our product candidates. Even if we conduct freedom to operate analyses, we would expect to do so only with respect to certain of our product candidates as they move through development. Accordingly, there may be third-party patents that would impair our ability to commercialize product candidates and we cannot assure you that we could obtain a license, or even if available, whether such license might be obtained on commercially reasonable terms. Even in those situations where we conduct a freedom to operate analysis, there can be no assurance that we would identify all relevant or necessary patents and patent applications that may apply to the manufacture and commercialization of our product candidates. Because patent applications can take many years to issue, there may be currently pending patent applications that may later result in issued patents that our product candidates may infringe, and if patents issue with respect to any such application and we become aware of such issuance, we would have to determine its impact on our efforts to develop and commercialize our product candidates and the strategy for obtaining a license or contesting any such issued patent.

Our product candidates marketed under NDAs may be subject to generic competition.

Although we are not currently involved in any intellectual property litigation, we may be involved in lawsuits to protect or enforce our patents or the patents of our licensors, which could be expensive, time consuming, and unsuccessful.

Although a substantial amount of our effort will focus on the continued clinical testing, potential approval, and commercialization of our existing product candidates, the success of our business is also expected to depend in part upon our ability to identify, license, discover, develop, or commercialize additional product candidates. Research programs to identify new product candidates require substantial technical, financial, and human resources. We may focus our efforts and resources on potential programs or product candidates that ultimately prove to be unsuccessful. Our research programs or licensing efforts may fail to yield additional product candidates for clinical development and commercialization for a number of reasons, including but not limited to the following:

•	~~our research or business development methodology or search criteria and process may be unsuccessful in identifying potential product candidates;~~

•	~~we may not be able or willing to assemble sufficient resources to acquire or discover additional~~•our research or business development methodology or search criteria and process may be unsuccessful in identifying potential product candidates;

•we may not be able or willing to assemble sufficient resources to acquire or discover additional product candidates;•

~~our product candidates may not succeed in preclinical or clinical testing;~~

•our product candidates may not succeed in preclinical or clinical testing;•

~~our potential product candidates may be shown to have harmful side effects or may have other characteristics that may make the products unmarketable or unlikely to receive marketing approval;~~

•our potential product candidates may be shown to have harmful side effects or may have other characteristics that may make the products unmarketable or unlikely to receive marketing approval;•

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

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

~~product candidates we develop may be covered by third parties’ patents or other exclusive rights;~~

•product candidates we develop may be covered by third parties’ patents or other exclusive rights;•

~~the market for a product candidate may change during our program so that such a product may become unreasonable to continue to develop;~~

•the market for a product candidate may change during our program so that such a product may become unreasonable to continue to develop;•

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

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

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

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

If any of these events occur, we may be forced to abandon our development efforts for a program or programs, or we may not be able to identify, license, discover, develop, or commercialize additional product candidates, which would have a material adverse effect on our business and could potentially cause us to cease operations.

Healthcare legislative reform measures may have a material adverse effect on our business and results of operations.

In the United States, there have been and continue to be a number of legislative initiatives to ~~contain~~reform the delivery and payment for healthcare ~~costs.~~items and services. For example, in March 2010, the Patient Protection and Affordable Care Act ~~as amended by the Health Care and Education Reconciliation Act (the “ACA”)~~(ACA) was passed, which substantially changed the way health care is financed by both governmental and private insurers, and significantly impacts the U.S. pharmaceutical industry. This law was designed to expand access to health insurance coverage for uninsured and underinsured individuals while at the same time containing overall healthcare costs. The framework of the ACA and other healthcare reforms continues to evolve as a result of executive, legislative, regulatory, and administrative developments. For example, for calendar years 2021 and 2022, the American Rescue Plan Act of 2021 temporarily increased premium tax credit assistance established under the ACA to help eligible individuals cover premiums for health insurance purchased through the health insurance marketplace and removed the 400% federal poverty level limit that otherwise applies for purposes of eligibility to receive premium tax credits. The Inflation Reduction Act of 2022(IRA) extended this increased tax credit assistance and removal of the 400% federal poverty limit through 2025. There have also

been ~~executive, judicial and Congressional~~legal challenges to ~~numerous provisions~~certain aspects of the ACA. While Congress has not passed comprehensive repeal legislation, it has enacted laws that modify certain provisions of the ACA such as removing penalties, starting January 1, 2019, for not complying with the ACA’s individual mandate to carry health insurance and delaying the implementation of certain ACA-mandated fees. In addition, the 2020 federal spending package permanently eliminated, effective January 1, 2020, the ACA-mandated “Cadillac” tax on high-cost employer-sponsored health coverage and medical device tax and, effective January 1,On June 17, 2021, also eliminated the health insurer tax. On December 14, 2018, a Texas U.S. District Court Judge ruled that the ACA is unconstitutional in its entirety because the “individual mandate” was repealed by Congress as part of the Tax Cuts and Jobs Act of 2017. Additionally, on December 18, 2019, the U.S. Court of Appeals for the 5th Circuit upheld the District Court ruling that that the individual mandate was unconstitutional and remanded the case back to the District Court to determine whether the remaining provisions of the ACA are invalid as well. The U.S. Supreme Court is currently reviewing this case, although it is unclear when a decision will be made. On February 10, 2021, the Biden administration withdrew the federal government’s support for overturning the ACA. Although the U.S. Supreme Court ~~has not yet ruled~~dismissed a recent judicial challenge to the ACA brought by several states without specifically ruling on the constitutionality of the ACA, on January 28, 2021, President Biden issued an executive order to initiate a special enrollment period for purposes of obtaining health insurance coverage through the ACA marketplace, which began on February 15, 2021 and will remain open through August 15, 2021. The executive order also instructs certain governmental agencies to review and reconsider their existing policies and rules that limit access to healthcare, including among others, reexamining Medicaid demonstration projects and waiver programs that include work requirements, and policies that create unnecessary barriers to obtaining access to health insurance coverage through Medicaid or the ACA. It is unclear how ~~the U.S. Supreme Court ruling, other such litigation, and~~ the healthcare reform measures of the Biden administration or other efforts, if any, to challenge, repeal, amend or replace the ACA will impact the ACA and our business.

Also, there has been heightened governmental scrutiny ~~recently~~ over pharmaceutical pricing practices in light of the rising cost of prescription drugs and biologics. Such scrutiny has resulted in ~~several recent~~ Congressional and federal agency inquiries regarding pricing and related practices, as well as proposed and enacted federal and state legislation and regulation designed to, among other things, bring more transparency to product pricing, review the relationship between pricing and manufacturer patient programs, and reform government program reimbursement methodologies for ~~products~~products. For example,, the ~~Trump administration used several means~~American Rescue Plan Act of 2021 included among its provisions a sunset of the ACA’s cap on pharmaceutical manufacturers’ rebate liability under the Medicaid Drug Rebate Program. Previously, under the ACA, manufacturers’ rebate liability was capped at 100% of the average manufacturer price for a covered outpatient drug. Effective January 1, 2024, manufacturers’ Medicaid Drug Rebate Program rebate liability will no longer be capped, potentially resulting in a manufacturer paying more in Medicaid Drug Rebate Program rebates than it receives on the sale of certain covered outpatient drugs. The Biden Administration has continued to ~~propose or implement~~support legislative reforms to lower prescription drug prices. In August 2022, President Biden signed into law the IRA, which implements substantial changes to the Medicare program, including drug pricing ~~reform, including through federal budget proposals, executive orders~~reforms and ~~policy initiatives. For example, on July 24, 2020 and September 13, 2020,~~changes to the Trump administration announced several executive orders related to drug pricing that seeks to implement several of the administration’s proposals. As a result, the FDA released a final rule on September 24, 2020, effective November 30, 2020, providing guidance for states to build and submit importation plans for drugs from Canada. Further, on November 20, 2020, HHS finalized a regulation removing safe harbor protection for price reductions from pharmaceutical manufacturers to plan sponsors underMedicare Part D ~~either directly~~benefit design.Among other reforms, the Inflation Reduction Act of 2022 imposes inflation rebates on drug manufacturers for products reimbursed under Medicare Parts B and D if the prices of those products increase faster than inflation; implements changes to the Medicare Part D benefit that, beginning in 2025, will cap benefit annual out-of-pocket spending at $2,000, while imposing new discount obligations for pharmaceutical manufacturers; and, beginning in 2026, establishes a “maximum fair price” for a fixed number of pharmaceutical and biological products covered under Medicare Parts B and D following a price negotiation process with the Centers for Medicare and Medicaid Services. The IRA explicitly excludes from price negotiation orphan drugs designated for only one rare disease or ~~through pharmacy benefit managers, unless~~condition and for which the only approved indication is for such disease or condition. However, those drugs with multiple orphan designations are not explicitly excluded from drug price ~~reduction is required by law. The implementation of~~negotiation. CMS continues to release guidance implementing the ~~rule has been delayed by~~IRA and the Biden administration continues to direct the Department of Health and Human Services to consider new healthcare payment and delivery models that would lower drug costs and promote access to innovative therapies for beneficiaries enrolled in the Medicare and Medicaid programs.We cannot predict the likelihood, nature or extent of healthcare or drug pricing reforms that may arise from ~~January 1, 2022~~future legislation or administration action nor can we predict how, or to ~~January 1, 2023 in response~~what extent, the drug pricing policies or future healthcare reforms will affect our products. However, we expect these initiatives to ongoing litigation. The rule also creates a new safe harbor for price reductions reflected at the point-of-sale, as well as a safe harbor for certain fixed fee arrangements between pharmacy benefit managers and manufacturers, the implementation of which have also been delayed until January 1, 2023. On November 20, 2020, CMS issued an interim final rule implementing President Trump’s Most Favored Nation executive order, which would tie Medicare Part B payments for certain physician-administered drugs to the lowest price paid in other economically advanced countries, effective January 1, 2021. On December 28, 2020, the United States District Court in Northern California issued a nationwide preliminary injunction against implementation of the interim final rule. It is unclear whether the Biden administration will work to reverse these measures or pursue similar policy initiatives. increase pressure on drug pricing.

At the state level, legislatures have increasingly passed legislation and implemented regulations designed to control pharmaceutical and biological product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing. Any ~~repeal and replace~~ legislation at the state or federal level aimed at further healthcare reform may have the effect of limiting the amounts that government agencies will pay for healthcare products and services. ~~Policy~~For example, an emerging trend at the state level is the establishment of prescription drug affordability boards, some of which will prospectively permit certain states to establish upper payment limits for drugs that the state has determined to be “high-cost”.In addition, policy changes, including potential modification or repeal of all or parts of the ACA or the implementation of new health care legislation, could result in significant

changes to the health care system, which may prevent us from being able to generate revenue, attain profitability or commercialize our drugs. We expect that additional state and federal healthcare reform measures will be adopted in the future, any of which could limit the amounts that federal and state governments will pay for healthcare products and services, which could result in reduced demand or lower pricing for our product candidates, or additional pricing pressures.

In the United States, the EU and other potentially significant markets for our product candidates, government authorities and third-party payors are increasingly attempting to limit or regulate the price of medical products and services, particularly for new and innovative products and therapies, which has resulted in lower average selling prices. For example, in the United States, there have been several recent Congressional inquiries and proposed bills designed to, among other things, bring more transparency to drug pricing, review the relationship between pricing and manufacturer patient programs, and reform government program reimbursement methodologies for drugs. Furthermore, theThe increased emphasis on managed healthcare in the United States and on country and regional pricing and reimbursement controls in the EU will put additional pressure on product pricing, reimbursement and usage, which may adversely affect our future product sales and results of operations. These pressures can arise from rules and practices of managed care groups, judicial decisions and governmental laws and regulations related to Medicare, Medicaid and healthcare reform, pharmaceutical reimbursement policies and pricing in general. Further, it is possible that additional governmental action is taken in response to the COVID-19 pandemic.

We may be subject, directly or indirectly, to foreign, federal and state healthcare fraud and abuse laws, false claims laws, and health information privacy and security laws. If we are unable to comply, or have not fully complied, with such laws, we could face substantial penalties, sanctions or other liability.

Our operations may be subject to various foreign, federal and state fraud and abuse laws, including, without limitation, the federal Anti-Kickback Statute, the federal False Claims Act, physician sunshine laws, the EU GDPR and/or the UK GDPR and other regulations. These laws may impact, among other things, our research, sales, marketing, education and ~~education~~patient assistance programs. In addition, we may be subject to patient privacy regulation by foreign, federal, and state governments in which we conduct our business. The laws that may affect our ability to operate include:

•

the federal Anti-Kickback Statute, which prohibits, among other things, persons from knowingly and willfully soliciting, receiving, offering or paying remuneration, directly or indirectly, to induce, or in return for, the purchase or recommendation of an item or service reimbursable under a federal healthcare program, such as the Medicare and Medicaid programs;

•the federal Anti-Kickback Statute, which prohibits, among other things, persons from knowingly and willfully soliciting, receiving, offering or paying anything of value as remuneration, directly or indirectly, to induce, or in return for, the purchase or recommendation of an item or service reimbursable under a federal healthcare program, such as the Medicare and Medicaid programs;•

federal civil and criminal false claims laws and civil monetary penalty laws, which prohibit, among other things, individuals or entities from knowingly presenting, or causing to be presented, claims for payment from Medicare, Medicaid, or other third-party payors that are false or fraudulent;

•federal civil and criminal false claims laws and civil monetary penalty laws, which prohibit, among other things, individuals or entities from knowingly presenting, or causing to be presented, claims for payment from Medicare, Medicaid, or other third-party payors that are false or fraudulent;•

~~HIPAA, which created new federal criminal statutes that prohibit executing a scheme to defraud any healthcare benefit program and making false statements relating to healthcare matters;~~

•HIPAA, which created new federal criminal statutes that prohibit executing a scheme to defraud any healthcare benefit program and making false statements relating to healthcare matters;•

HIPAA and its implementing regulations impose certain requirements on certain covered entity healthcare providers, health plans, and healthcare clearinghouse and their business associates that perform certain services involving the use or disclosure of individually identifiable health information as well as their covered subcontractors, relating to the privacy, security, and transmission of individually identifiable health information;

•HIPAA and its implementing regulations impose certain requirements on certain covered entity healthcare providers, health plans, and healthcare clearinghouse and their business associates that perform certain services involving the use or disclosure of individually identifiable health information as well as their covered subcontractors, relating to the privacy, security, and transmission of individually identifiable health information;•

The Physician Payments Sunshine Act, which requires manufacturers of drugs, devices, biologics, and medical supplies to report annually to HHS information related to payments and other transfers of value to physicians (defined to include doctors, dentists, optometrists, podiatrists, and chiropractors) and teaching hospitals, and ownership and investment interests held by physicians and their immediate family members and applicable group purchasing organizations. Beginning in 2022, such obligations will include payments and other transfers of value provided in the previous year to certain other healthcare professionals, including physician assistants, nurse practitioners, clinical nurse specialists, anesthesiologist assistants, certified nurse anesthetists, and certified nurse-midwives;

•The Physician Payments Sunshine Act, which requires manufacturers of drugs, devices, biologics, and medical supplies to report annually to HHS information related to payments and other transfers of value to physicians (defined to include doctors, dentists, optometrists, podiatrists, and chiropractors), teaching hospitals, physician assistants, nurse practitioners, clinical nurse specialists, anesthesiologist assistants, certified registered nurse anesthetists, and certified nurse midwives, as well as ownership and investment interests held by physicians and their immediate family members and applicable group purchasing organizations;•

~~the Federal Food, Drug, and Cosmetic Act (FDCA), which, among other things, prohibits the adulteration and misbranding of drugs and biological products;~~

•the Federal Food, Drug, and Cosmetic Act (FDCA), which, among other things, prohibits the adulteration and misbranding of drugs and biological products;•

state law equivalents of each of the above federal laws, such as anti-kickback and false claims laws that may apply to items or services reimbursed by any third-party payors, including commercial insurers, state laws that require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government, or otherwise restrict payments that may be made to healthcare providers and other potential referral sources; state laws that 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 local laws requiring the registration of pharmaceutical sales representatives; and state laws governing the privacy and security of health information in certain circumstances, many of which differ from each other in significant ways and may not have the same effect, thus complicating compliance efforts; and

•state law equivalents of each of the above federal laws, such as anti-kickback and false claims laws that may apply to items or services reimbursed by any third-party payors, including commercial insurers, state laws that require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government, or otherwise restrict payments that may be made to healthcare providers and other potential referral sources; state laws that 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 local laws requiring the registration of pharmaceutical sales representatives; and state laws governing the privacy and security of health information in certain circumstances, many of which differ from each other in significant ways and may not have the same effect, thus complicating compliance efforts; and federal and state laws requiring the disclosure of certain drug pricing information; and

•the EU GDPR and/or the UK GDPR (together, GDPR) and other EU Member State or English data protection legislation, which require data controllers and processors to (i) implement administrative, physical, technical, and organizational safeguards to protect personal information; (ii) establish an appropriate and valid legal basis for processing personal information (iii) comply with accountability transparency requirements regarding the processing of personal information, which require controllers to demonstrate and record compliance with the GDPR and to provide more detailed information to data subjects regarding processing; (iv) comply with data protection rights of data subjects including a right of access to and rectification of personal information, a right to obtain restriction of processing or to object to processing of personal information, a right to ask for a copy of personal information to be provided to a third party in a useable format and erasing personal information in certain circumstances; (v) report certain personal data breaches to the relevant supervisory authority without undue delay (and no later than 72 hours, where feasible); (vi) obtain explicit consent for collection of sensitive personal information such as health data; and (vii) consider data protection as any new products or services are developed and to limit the amount of personal information processed. In addition, the GDPR prohibits the international transfer of personal information outside of the EU and/or the UK including to the U.S., unless made to a country•

the EU GDPR and/or the UK GDPR (together, GDPR) and other EU Member State or English data protection legislation, which require data controllers and processors to (i) implement administrative, physical, technical, and organizational safeguards to protect personal information; (ii) establish an appropriate and valid legal basis for processing personal information (iii) comply with accountability transparency requirements regarding the processing of personal information, which require controllers to demonstrate and record compliance with the GDPR and to provide more detailed information to data subjects regarding processing ; (iv) comply with data protection rights of data subjects including a right of access to and rectification of personal information, a right to obtain restriction of processing or to object to processing of personal information, a right to ask for a copy of personal information to be provided to a third party in a useable format and erasing personal information in certain circumstances; (v) report certain personal data breaches to the relevant supervisory authority without undue delay (and no later than 72 hours, where feasible); (vi) obtain explicit consent for collection of sensitive personal information such as health data; and (vii) consider data protection as any new products or services are developed and to limit the amount of personal information processed. In addition, the GDPR prohibits the international transfer of personal information outside of the EU and/or the UK including to the U.S., unless made to a country deemed to have adequate data privacy laws by the European Commission and/or the UK or a data transfer mechanism in accordance with the GDPR (as applicable) has been put in place.

deemed to have adequate data privacy laws by the European Commission and/or the UK or a data transfer mechanism in accordance with the GDPR (as applicable) has been put in place.

Because of the breadth of these laws and the narrowness of the statutory exceptions and safe harbors available, it is possible that some of our business activities could be subject to challenge under one or more of such laws. In addition, recent health care reform legislation has strengthened these laws.

If our operations are found to be in violation of any of the laws described above or any other governmental regulations that apply, we may be subject to penalties, including significant civil, criminal and administrative penalties, damages, disgorgement, fines, sanctions, exclusion from participation in government health care programs, such as Medicare and Medicaid, imprisonment, corporate integrity oversight and reporting obligations, contractual damages, reputational harm, diminished profits and future earnings, and the curtailment or restructuring of our operations, any of which could adversely affect our ability to operate our business and our results of operations.

If we fail to comply with our reporting and payment obligations under the Medicaid Drug Rebate Program or other governmental pricing programs in the US, we could be subject to additional rebate or discount requirements, fines, sanctions and exposure under other laws which could have an adverse effect on our business, results of operations and financial condition.

The Company’s product is subject to government mandated rebates under the Medicaid Drug Rebate Program and other government health care programs in the United States. These programs generally require us to pay rebates or otherwise provide discounts to government payors in connection with drugs that are dispensed to beneficiaries of these programs. In some cases, such as with the Medicaid Drug Rebate Program, rebates are calculated based on pricing metrics we are required to report on a monthly and quarterly basis to the government agencies that administer the programs. These pricing metrics are complex and may vary across products and programs. Additionally, the requirements of government health care programs change frequently and are often subject to interpretation by regulatory agencies and the courts. Tracking these updates and maintaining compliance will be costly and time consuming. Further, errors in the submission of our pricing data, failure to make necessary pricing disclosures, and/or overcharging government payors (or failing to identify overpayments) could result in allegations against us under the federal False Claims Act and other laws and regulations, as well as subject us to potential termination of our rebate agreement with CMS. Responding to government investigations or enforcement actions and/or making necessary refunds to government payors would be expensive and time consuming and could have an adverse effect on our business, results of operations and financial condition.

The withdrawal of the United Kingdom from the EU, commonly referred to as “Brexit,” may adversely impact our ability to obtain regulatory approvals of our product candidates in the EU, result in restrictions or imposition of taxes and duties for importing our product candidates into the EU, and may require us to incur additional expenses in order to develop, manufacture and commercialize our product candidates in the EU.

In June 2016, the electorate in the UK voted in favor of leaving the EU (commonly referred to as “Brexit”). Thereafter, in March 2017, the country formally notified the EU of its intention to withdraw pursuant to Article 50 of the Lisbon Treaty and the UK formally left the EU on January 31, 2020. A transition period began on February 1, 2020, during which EU pharmaceutical law remained applicable to the UK. This transition period ended on December 31, 2020.

The EU-UK Trade and Cooperation Agreement (TCA) was agreed on December 24, 2020. The UK and EU agreed that the TCA would apply provisionally from January 1, 2021, the TCA was ratified on April 30, 2021 and came into force on May 1, 2021.

Since the regulatory framework in the UK covering the quality, safety and efficacy of pharmaceutical products, clinical trials, marketing authorization, commercial sales and distribution of pharmaceutical products is derived from EU Directives and Regulations, Brexit could materially impact the future regulatory regime which applies to products and the approval of product candidates in the UK, as UK legislation now has the potential to diverge from EU legislation. It remains to be seen how Brexit will fully impact regulatory requirements for product candidates and products in the UK in the long-term.

~~The UK Medicines and Healthcare products Regulatory Agency (MHRA) has published detailed guidance for industry and organizations to follow from January 1, 2021 now~~

At present, the ~~transition period is over, which will be updated as the UK’s regulatory position on medicinal products evolves over time. The~~ regulatory framework for medicines that existed before the end of the transition period has effectively been preserved in UK domestic legislation as ‘retained EU law’ which has prevented substantial divergence to the regulation of ~~medicines.~~medicines so far. However, ~~some changes to~~ the UK ~~legislation have been immediately necessary, including~~Government has now introduced the ~~implementation~~Retained EU Law (Revocation and Reform) Bill 2022 which intends to end the “special status” of retained EU law under UK law. If enacted into law, this would facilitate departure from retained EU law, and may lead to greater regulatory divergence between the EU and UK in the future. In comparison, as matters currently stand, under the terms of the Northern Ireland Protocol ~~(NIP)~~(the NIP), ~~pursuant to which,~~implemented by the EU ~~pharmaceutical legal framework acquis continues~~(Withdrawal Agreement) Act 2020, Northern Ireland is treated for the same purposes as if it were still an EU Member

State, and must remain aligned to ~~apply~~the EU single market and customs rules. The UK government has also introduced a bill ‘Northern Ireland Protocol Bill’ which if enacted into law would enable the government to unilaterally disapply parts of the NIP which may lead to changes to the regulatory environment in Northern Ireland, ~~(subject~~and may trigger retaliatory measures against the UK by the EU. However, on February 27, 2023, the UK government and the EU Commission reached political agreement on a package of proposed amendments to ~~periodic consent of~~the NIP (Windsor Framework). According to the UK government, if these proposals are implemented, this would lead to a “carve-out from EU rules” and, amongst other measures, the UK medicines regulator (MHRA) would be responsible for approving medicines for the whole UK market, meaning that medicinal products available in Northern Ireland will not have to comply with EU law but rather with UK law, so medicinal products would be able to freely circulate between Northern Ireland and Great Britain. Furthermore, the UK government has said that it will withdraw the Northern Ireland ~~Legislative Assembly), and only products compliant with EU law can be placed~~Protocol Bill under the Windsor Framework if it is implemented. The future regulatory framework for medicines in ~~the~~ Northern Ireland ~~market - adding~~will remain uncertain until the proposals are passed into law. The EU-UK Trade and Cooperation Agreement allows for future deviation from the current regulatory framework and it is not known if and/or when any deviations may occur, which may have an ~~extra layer of regulatory complexity. As companies~~impact on Eiger’s business.

Companies now need to comply with a separate UK regulatory legal framework in order to commercialize medicinal products in Great Britain (namely, England, Wales and Scotland, as EU law ~~continues to apply~~currently applies in Northern Ireland). For instance, Great Britain will no longer be covered by centralized marketing authorizations ~~(under~~(as matters stand, under the Northern Irish Protocol, centralized marketing authorizations will continue to be recognized in Northern Ireland). All medicinal products with a current centralized marketing authorization were automatically converted to Great Britain marketing authorizations on January 1, 2021. For a period of ~~two~~three years from January 1, 2021, the MHRA may rely on a decision taken by the European Commission on the approval of a new marketing authorization in the centralized procedure, in order to more quickly grant a new Great Britain marketing authorization. A separate application will, however, still be required.

The ~~UK government is currently trying~~MHRA has also introduced new procedures aimed at accelerating regulatory approvals and time to ~~renegotiate fundamental aspects of the Northern Ireland Protocol so this is an unpredictable area for companies in the near future. The Trade and Cooperation Agreement signed between the UK~~market, including ‘rolling reviews’ and the ~~EU allows~~Innovative Licensing and Access Pathway (ILAP) although eligibility requirements apply.

The TCA and the proposed Bills allow for future deviation from the current regulatory framework and it is not known if and/or when any deviations may occur, which may have an impact on development, manufacture, marketing authorization, commercial sales and distribution of pharmaceutical products.

Our employees, principal investigators, consultants and commercial partners may engage in misconduct or other improper activities, including non-compliance with regulatory standards and requirements and insider trading.

We are exposed to the risk of fraudulent conduct or other illegal activity by our employees, independent contractors, principal investigators, consultants, commercial partners and vendors. Misconduct by these parties could include intentional, reckless and/or negligent conduct that fails to: comply with the regulations of the FDA and non-U.S. regulators, provide accurate information to the FDA and non-U.S. regulators, comply with healthcare fraud and abuse laws in the United States and abroad, report financial information or data accurately or disclose unauthorized activities to us. In particular, promotion, sales, marketing and certain business arrangements in the healthcare industry are subject to extensive laws intended to prevent fraud, misconduct, kickbacks, self-dealing and other abusive practices. These laws may restrict or prohibit a wide range of pricing, discounting, marketing and promotion, sales commission, customer incentive programs and other business arrangements. Such misconduct could also involve the improper use of information obtained in the course of patient recruitment or clinical trials, which could result in regulatory sanctions and cause serious harm to our reputation. We have adopted a code of business conduct and ethics applicable to all of our employees, but it is not always possible to identify and deter employee misconduct, and the precautions we take to detect and prevent this activity may not be effective in controlling unknown or unmanaged risks or losses or in protecting us from governmental investigations or other actions or lawsuits stemming from a failure to comply with these laws or 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.

We face potential product liability, and, if successful claims are brought against us, we may incur substantial liability and costs. If the use or misuse of our product candidates harm patients or is perceived to harm patients even when such harm is unrelated to our product candidates, our regulatory approvals could be revoked or otherwise negatively impacted, and we could be subject to costly and damaging product liability claims.

The use or misuse of our product candidates in clinical trials and the sale of any products for which we obtain marketing approval exposes us to the risk of product liability claims. Product liability claims might be brought against us by consumers, healthcare providers, pharmaceutical companies or others selling or otherwise coming into contact with our

products. There is a risk that our product candidates may induce adverse events. If we cannot successfully defend against product liability claims, we could incur substantial liability and costs. In addition, regardless of merit or eventual outcome, product liability claims may result in:

•	~~impairment of our business reputation;~~

•impairment of our business reputation;•

~~initiation of investigations by regulators;~~

•initiation of investigations by regulators;•

~~withdrawal of clinical trial participants;~~

•withdrawal of clinical trial participants;•

~~costs due to related litigation;~~

•costs due to related litigation;•

~~distraction of management’s attention from our primary business;~~

•distraction of management’s attention from our primary business;•

~~substantial monetary awards to patients or other claimants;~~

•substantial monetary awards to patients or other claimants;•

~~the inability to commercialize our product candidates;~~

•the inability to commercialize our product candidates;•

~~product recalls, withdrawals or labeling, marketing or promotional restrictions; and~~

•product recalls, withdrawals or labeling, marketing or promotional restrictions; and•

~~decreased demand for our product candidates, if approved for commercial sale.~~

•decreased demand for our product candidates, if approved for commercial sale.

We believe our current product liability insurance coverage is appropriate in light of our clinical programs; however, we may not be able to maintain insurance coverage at a reasonable cost or in sufficient amounts to protect us against losses due to liability. If and when we obtain marketing approval for product candidates, we intend to increase our insurance coverage to include the sale of commercial products; however, we may be unable to obtain product liability insurance on commercially reasonable terms or in adequate amounts. On occasion, large judgments have been awarded in class action lawsuits based on drugs or medical treatments that had unanticipated adverse effects. A successful product liability claims or series of claims brought against us could cause our stock price to decline and, if judgments exceed our insurance coverage, could adversely affect our results of operations and business.

Patients with the diseases targeted by our product candidates are often already in severe and advanced stages of disease and have both known and unknown significant pre-existing and potentially life-threatening health risks. During the course of treatment, patients may suffer adverse events, including death, for reasons that may or may not be related to our product candidates. Such events could subject us to costly litigation, require us to pay substantial amounts of money to injured patients, delay, negatively impact or end our opportunity to receive or maintain regulatory approval to market our products, or require us to suspend or abandon our commercialization efforts. Even in a circumstance in which we do not believe that an adverse event is related to our products, the investigation into the circumstance may be time-consuming or inconclusive. These investigations may interrupt our sales efforts, delay our regulatory approval process in other countries, or impact and limit the type of regulatory approvals our product candidates receive or maintain. As a result of these factors, a product liability claim, even if successfully defended, could have a material adverse effect on our business, financial condition or results of operations.

If we fail to comply with environmental, health and safety laws and regulations, we could become subject to fines or penalties or incur costs that could have a material adverse effect on the success of our business.

Our research and development activities and our third-party manufacturers’ and suppliers’ activities involve the controlled storage, use, and disposal of hazardous materials, including the components of our product candidates and other hazardous compounds. We and our manufacturers and suppliers are subject to laws and regulations governing the use, manufacture, storage, handling, and disposal of these hazardous materials. In some cases, these hazardous materials and various wastes resulting from their use are stored at our and our manufacturers’ facilities pending their use and disposal. We cannot eliminate the risk of contamination, which could cause an interruption of our commercialization efforts, research and development efforts and business operations, environmental damage resulting in costly clean-up and liabilities under applicable laws and regulations governing the use, storage, handling, and disposal of these materials and specified waste products. Although we believe that the safety procedures utilized by our licensors and our third-party manufacturers for handling and disposing of these materials generally comply with the standards prescribed by these laws and regulations, we cannot guarantee that this is the case or eliminate the risk of accidental contamination or injury from these materials. In such an event, we may be held liable for any resulting damages and such liability could exceed our resources and state or federal or other applicable authorities may curtail our use of certain materials and/or interrupt our business operations. Furthermore, environmental laws and regulations are complex, change frequently, and have tended to become more stringent. We cannot predict the impact of such changes and cannot be certain of our future compliance. We do not currently carry biological or hazardous waste insurance coverage.

We are currently conducting and will continue to conduct clinical trials in foreign countries, which could expose us to risks that could have a material adverse effect on the success of our business and the delivery of clinical trial data.

We have conducted in the past and are currently conducting clinical trials in the United States, Canada, Australia, Turkey, Germany, Pakistan, New Zealand, Mongolia, Spain, France, Bulgaria, Romania, Taiwan, Sweden, Italy, Belgium, Switzerland, United Kingdom, Greece, Moldova, Ukraine, Russia, and Israel, and accordingly, we are subject to risks associated with doing business globally, including commercial, political, and financial risks. Emerging regions, such as Eastern Europe, Latin America, Asia, and Africa, as well as more developed markets, such as the United Kingdom, France, Germany, and Australia, provide clinical study opportunities for us. In addition, we are subject to potential disruption caused by military conflicts; potentially unstable governments or legal systems; civil or political upheaval or unrest; local labor policies and conditions; possible expropriation, nationalization, or confiscation of assets; problems with repatriation of foreign earnings; economic or trade sanctions; closure of markets to imports; anti-American sentiment; terrorism or other types of violence in or outside the United States; health pandemics; and a significant reduction in global travel. For example, both Turkey and Pakistan are key regions for clinical activity relating to Hepatitis Delta Virus, and further outbreaks of violence and political instability in the region could disrupt our clinical operations or otherwise limit our ability to access or conduct clinical studies in those regions. Certain countries have closed their borders due to COVID-19 preventing activation of clinical sites. ~~Recent actions~~Actions taken by the Russian Federation in Ukraine and surrounding areas have destabilized the region and caused the adoption of comprehensive sanctions by, among others, the EU, the United States and the UK, which restrict a wide range of trade and financial dealings with Russia and Russian persons, as well as certain regions in Ukraine, including by imposing stricter export controls, prohibiting dealings with major Russian banks and credit institutions, and prohibiting trade with the Donetsk, Luhansk, Kherson and ~~Luhansk~~Zaporizhzhia regions of Ukraine. In addition, clinical site initiation and patient enrollment may be delayed, and we may not be able to access sites for initiation, monitoring and data collection in regions affected by the Russian invasion of Ukraine, including due to the prioritization of hospital resources away from clinical trials or as a result of ~~government imposed~~government-imposed curfews, warfare, violence or other governmental action or events that restrict movement. Some patients may not be able to comply with clinical trial protocols if the conflict impedes patient movement or interrupts healthcare services. We could also experience disruptions in our supply chain or limits to our ability to obtain sufficient materials for our ~~drug~~ products in certain regions. D-LIVR is a global Phase 3 trial that has enrolled 407 patients across 116 clinical trial sites in 22 countries, including five sites in Ukraine. While we believe that the study is more than adequately powered to demonstrate statistical significance over placebo even if patients from Ukraine discontinue from the study, impacts related to the Russian invasion of Ukraine may have a material adverse effect on our ability to adequately conduct the D-LIVR trial in the region. Our success will depend, in part, on our ability to overcome the challenges we encounter with respect to these risks and other factors affecting U.S. companies with global operations. If our global clinical trials were to experience significant disruption due to these risks or for other reasons, it could have a material adverse effect on our operations and prospects.

We or the third parties upon whom we depend may be adversely affected by earthquakes, natural epidemics or other natural disasters and our business continuity and disaster recovery plans may not adequately protect us from a serious disaster.

Earthquakes, health epidemics or other natural disasters could severely disrupt our operations and have a material adverse effect on our business. If a natural disaster, power outage or other event occurred that prevented us from using all or a significant portion of our headquarters, damaged critical infrastructure, such as the manufacturing facilities of our third-party CMOs, or otherwise disrupted operations, it may be difficult or, in certain cases, impossible for us to continue our business for a substantial period of time. For example, in December 2019, an outbreak of a novel strain of coronavirus (COVID-19) originated in Wuhan, China. Since certain starting materials of certain of our products obtained from third-party chemical suppliers are manufactured in China and Japan, an outbreak of communicable diseases in the region, or the perception that such an outbreak could occur, and the measures taken by the governments of countries affected, could adversely affect our business, financial condition or results of operations by limiting our ability to manufacture product within or outside for example China, Japan, Italy, Canada, and the United States, forcing temporary closure of facilities that we rely upon or increasing the costs associated with obtaining starting materials and then clinical supplies of our product candidates. The extent to which the coronavirus impacts our results will depend on future developments, which are highly uncertain and cannot be accurately predicted, including new information which may emerge concerning the severity of the coronavirus and the actions to contain the coronavirus or treat its impact, among others. In addition, our corporate headquarters is located in the San Francisco Bay Area, which has in the past experienced severe earthquakes, ~~and~~ other natural disasters, and ~~is currently experiencing~~ an outbreak of COVID-19. We do not carry earthquake insurance. We have limited disaster recovery and business continuity plans in place currently and our business would be impaired in the event of a serious disaster or similar event. We may incur substantial expenses to develop and implement any disaster recovery and business continuity plans, which could have a material adverse effect on our business.

Our business is currently adversely affected by and could be materially adversely affected in the future by the effects of disease outbreaks, epidemics and pandemics including the evolving effects of the COVID-19 outbreak. We have a significant number of clinical trial sites in countries that have been directly affected by COVID-19. We depend on manufacturing operations for various stages of our supply chain in countries that have been directly affected by COVID-19. COVID-19 continues to adversely affect our business and could materially and adversely affect our operations and those of our manufacturers and other third parties with whom we conduct business.

Our business has been adversely affected by COVID-19 and could be materially and adversely impacted by COVID-19 or other health epidemics in regions where we have significant manufacturing facilities, concentrations of clinical trial sites or other business operations.

The COVID-19 pandemic has presented a substantial public health and economic challenge around the world and is affecting employees, patients, community and business operations, as well as the U.S. economy and financial markets. Theongoing effects of the pandemic and government and other responses thereto, including shelter-in-place orders and our work-from-home policies, may continue to negatively impact productivity, disrupt our business and delay our clinical programs and timelines, the magnitude of which will depend, in part, on the length and severity of ~~the~~any restrictions and other limitations on our ability to conduct our business in the ordinary course. These and similar, and perhaps more severe, disruptions in our operations could negatively impact our business, operating results and financial condition.

Additionally, some of our suppliers of certain materials used in the production of our drug products are located in China, Japan, Canada, Italy and the United States. While many of these materials may be obtained by more than one supplier, including suppliers outside of China, Japan, Canada, Italy and the United States, port closures and other restrictions resulting from the coronavirus outbreak in the region may disrupt our supply chain or limit our ability to obtain sufficient materials for our drug products.

In addition, our clinical trials have been and may continue to be affected by the COVID-19 pandemic. Site initiation and patient enrollment has been delayed, due to prioritization of hospital resources toward the COVID-19 pandemic, travel restrictions imposed by governments, and the inability to access sites for initiation and monitoring. In our D-LIVR trial, the COVID-19 pandemic has delayed enrollment in our global clinical trial, some patients may not be able to comply with clinical trial protocols if quarantines impede patient movement or interrupt healthcare services, we may be unable to obtain blood samples for testing, and we may not be able to provide study drug to patients.

Further, as a result of the COVID-19 pandemic, the extent and length of which is uncertain, we may be required to develop and implement additional clinical study policies and procedures designed to help protect study participants from the COVID-19 virus, which may include using telemedicine visits, remote monitoring of patients and clinical sites, and measures to ensure that data from clinical studies that may be disrupted as result of the pandemic are collected pursuant to the study protocol and consistent with GCPs, with any material protocol deviation reviewed and approved by the site IRB. Missed scheduled patient appointments, any interruption in study drug supply, or other consequences that may result in incomplete data being generated during a study as a result of the pandemic must be adequately documented

The FDA and ~~justified. For example, on March 18, 2020, the FDA issued guidance on conducting~~

~~clinical trials during the pandemic, which describes a number of considerations for sponsors of clinical trials impacted by the pandemic, including the requirement to include~~EMA have in the clinical study report (or as a separate document) contingency measures implemented to manage the study, any disruption of the study as a result of the COVID-19 pandemic; a list of all study participants by unique subject identifier and by investigational site that were affected by the COVID-19 pandemic, and a description of how the individual’s participation was altered; and analyses and corresponding discussions that address the impact of implemented contingency measures (e.g., participant discontinuation from investigational product and/or study, alternative procedures used to collect critical safety and/or efficacy data) on the safety and efficacy results reported for the study.

~~Further, the FDA and EMA~~past suspended, may continue to suspend, prioritize or delay certain foreign inspections, and if there continues to be a suspension or delay in inspections, our product application reviews and potential approvals could be impacted or delayed. In response to the COVID-19 pandemic, on March 10, 2020 the FDA announced its intention to postpone most inspections of foreign manufacturing facilities. On March 18, 2020, the FDA announced its intention to temporarily postpone routine surveillance inspections of domestic manufacturing facilities and provided guidance regarding the conduct of clinical trials. Subsequently, on July 10, 2020, the FDA announced its intention to resume certain on-site inspections of domestic manufacturing facilities subject to a risk-based prioritization system. In May 2021, the FDA updated its guidance, first published in August 2020, clarifying how it intends to conduct inspections during the COVID-19 pandemic, including how it plans to determine which inspections are “mission critical.” In November 2021, FDA provided an update to the May 2021 “Resiliency Roadmap for FDA Inspectional Oversight” noting completion of “mission critical” work over the previous year. In the update, FDA noted that it “is continuing to complete mission-critical work, prioritize other higher-tiered inspectional needs (e.g., for-cause inspections), and carry out surveillance inspections using risk-based approaches for evaluating public health impact.” Further, ongoing surges in COVID-19 case numbers with the emergence of new variants ~~(e.g., the Omicron variant in late 2021)~~and sub-variants have contributed to interruptions in FDA’s surveillance ~~capabilities. In light~~capabilities, and such disruptions may persist in the future as a result of ~~high positivity rates and hospitalizations, FDA made temporary changes in late 2021, including temporarily postponing certain inspection activities from December 29, 2021 to January 19, 2022.~~ ~~On February 2, 2022, FDA announced that it would resume domestic surveillance inspections across all product areas on February 7, 2022.~~future surges. We cannot predict whether, and when, FDA will decide to pause or resume inspections due to the COVID-19 pandemic.

The FDA intends to use the roadmap as a risk-based assessment system to identify the categories of regulatory activity that can occur within a given geographic area, ranging from mission critical inspections to resumption of all regulatory activities. On-going surges, new variants, or additional factors may further affect inspection timelines.

Regulatory authorities outside the United States may adopt similar restrictions or other policy measures in response to the COVID-19 pandemic, including providing guidance regarding the conduct of clinical trials. If global health concerns continue to prevent the FDA or other regulatory authorities from conducting their regular inspections, or impact reviews or other regulatory activities, it could significantly impact the ability of the FDA or other foreign regulatory authorities to timely review and process our regulatory submissions, which could have a material adverse effect on our business.

While we expect the COVID-19 pandemic to continue to adversely affect our business operations, the extent of the impact on our clinical development and regulatory efforts and the value of and market for our common stock will depend on future developments that are highly uncertain and cannot be predicted with confidence at this time, such as the ultimate duration of the pandemic, travel restrictions, quarantines, social distancing and business closure requirements in the U.S. and in other countries, and the effectiveness of actions taken globally to contain and treat COVID-19. In addition, to the extent the ongoing COVID-19 pandemic adversely affects our business and results of operations, it may also have the effect of heightening many of the other risks and uncertainties described elsewhere in this ‘‘Risk Factors’’ section.

Risks Related to Ownership of our Common Stock

The market price of our common stock has been and may continue to be highly volatile, and you may not be able to resell some or all of your shares at a desired market price.

The market price of our common stock has been and is likely to continue to be volatile. Our stock price could be subject to wide fluctuations in response to a variety of factors, including the following:

•	~~results or delays in preclinical studies or clinical trials;~~

•results or delays in preclinical studies or clinical trials;•

~~our decision to initiate a clinical trial, not to initiate a clinical trial or to terminate an existing clinical trial;~~

•our decision to initiate a clinical trial, not to initiate a clinical trial or to terminate an existing clinical trial;•

~~unanticipated serious safety concerns related to the use of any of our product candidates;~~

•unanticipated serious safety concerns related to the use of any of our product candidates;•

~~reports of adverse events in other gene therapy products or clinical trials of such products;~~

•reports of adverse events in other gene therapy products or clinical trials of such products;•

~~inability to obtain additional funding;~~

•inability to obtain additional funding;•

~~any delay in filing an IND, NDA, BLA, or MAA for any of our product candidates and any adverse development or perceived adverse development with respect to the FDA’s review of that IND, NDA, or BLA;~~

•any delay in filing an IND, NDA, BLA, or MAA for any of our product candidates and any adverse development or perceived adverse development with respect to the FDA’s review of that IND, NDA, or BLA(or the EMA’s review of that MAA);•

~~our ability to obtain regulatory approvals for our product candidates, and delays or failures to obtain such approvals;~~

•our ability to obtain regulatory approvals for our product candidates, and delays or failures to obtain such approvals;•

~~failure of any of our product candidates, if approved, to achieve commercial success;~~

•failure of any of our product candidates, if approved, to achieve commercial success;•

~~failure to obtain Orphan Drug designation;~~

•failure to obtain or maintain Orphan Drug designation;•

~~failure to maintain our existing third-party license and supply agreements;~~

•failure to maintain our existing third-party license and supply agreements;•

~~failure by our licensors to prosecute, maintain, or enforce our intellectual property rights;~~

•failure by our licensors to prosecute, maintain, or enforce our intellectual property rights;•

~~changes in laws or regulations applicable to our product candidates;~~

•changes in laws or regulations applicable to our product candidates;•

~~any inability to obtain adequate supply of our product candidates or the inability to do so at acceptable prices;~~

•any inability to obtain adequate supply of our product candidates or the inability to do so at acceptable prices;•

~~adverse regulatory authority decisions;~~

•adverse regulatory authority decisions;•

~~introduction of new products, services, or technologies by our competitors;~~

•introduction of new products, services, or technologies by our competitors;•

~~failure to meet or exceed financial and development projections we may provide to the public;~~

•failure to meet or exceed financial and development projections we may provide to the public;•

~~failure to meet or exceed the financial and development projections of the investment community;~~

•	~~the perception~~•failure to meet or exceed the financial and development projections of ~~the pharmaceutical industry by the public, legislatures, regulators, and~~ the investment community;

•the perception of the pharmaceutical industry by the public, legislatures, regulators, and the investment community;•

~~announcements of significant acquisitions, strategic partnerships, joint ventures, or capital commitments by us or our competitors;~~

•announcements of significant acquisitions, strategic partnerships, joint ventures, or capital commitments by us or our competitors;•

~~disputes or other developments relating to proprietary rights, including patents, litigation matters, and our ability to obtain patent protection for our technologies;~~

•disputes or other developments relating to proprietary rights, including patents, litigation matters, and our ability to obtain patent protection for our technologies;•

~~additions or departures of key personnel;~~

•additions or departures of key personnel;•

~~significant lawsuits, including patent or stockholder litigation;~~

•significant lawsuits, including patent or stockholder litigation;•

~~if securities or industry analysts do not publish research or reports about our business, or if they issue adverse or misleading opinions regarding our business and stock;~~

•if securities or industry analysts do not publish research or reports about our business, or if they issue adverse or misleading opinions regarding our business and stock;•

~~changes in the market valuations of similar companies;~~

•changes in the market valuations of similar companies;•

~~general market or macroeconomic conditions;~~

•general market or macroeconomic conditions;•

~~sales of our common stock by us or our stockholders in the future;~~

•sales of our common stock by us or our stockholders in the future;•

~~trading volume of our common stock;~~

•trading volume of our common stock;•

~~announcements by commercial partners or competitors of new commercial products, clinical progress or the lack thereof, significant contracts, commercial relationships or capital commitments;~~

•announcements by commercial partners or competitors of new commercial products, clinical progress or the lack thereof, significant contracts, commercial relationships or capital commitments;•

~~adverse publicity relating to the hepatitis market generally, including with respect to other products and potential products in such markets;~~

•adverse publicity relating to the hepatitis market generally, including with respect to other products and potential products in such markets;•

~~the introduction of technological innovations or new therapies that compete with potential products of ours;~~

•the introduction of technological innovations or new therapies that compete with potential products of ours;•

~~changes in the structure of health care payment systems; and~~

•changes in the structure of health care payment systems; and•

~~period-to-period fluctuations in our financial results.~~

•period-to-period fluctuations in our financial results.

Moreover, the stock markets in general have experienced substantial volatility that has often been unrelated to the operating performance of individual companies, including very recently in connection with the ongoing COVID-19 pandemic, which has resulted in decreased stock prices for many companies notwithstanding the lack of a fundamental change in their underlying business models or prospects. These broad market and industry factors, including potentially worsening economic conditions and other adverse effects or developments relating to the ongoing COVID-19 pandemic, may also adversely affect the trading price of our common stock.

In the past, following periods of volatility in the market price of a company’s securities, stockholders have often instituted class action securities litigation against those companies. Such litigation, if instituted, could result in substantial costs and diversion of management attention and resources, which could significantly harm our profitability and reputation.

We will incur costs and demands upon management as a result of complying with the laws and regulations affecting public companies.

We have incurred and will continue to incur significant legal, accounting and other expenses associated with public company reporting requirements. We also incur costs associated with corporate governance requirements, including requirements under the Sarbanes-Oxley Act, as well as rules implemented by the SEC and The Nasdaq Stock Market LLC. These rules and regulations impose significant legal and financial compliance costs and make some activities more time-consuming and costly. For example, our management team consists of certain executive officers who have not previously managed and operated a public company. These executive officers and other personnel will need to devote substantial time to gaining expertise regarding operations as a public company and compliance with applicable laws and regulations. In addition, it may be more difficult for us to attract and retain qualified individuals to serve on our board of directors or as executive officers, which may adversely affect investor confidence and could cause our business or stock price to suffer.

Anti-takeover provisions in our charter documents and under Delaware law could make an acquisition of us more difficult and may prevent attempts by our stockholders to replace or remove our management.

Provisions in our certificate of incorporation and bylaws may delay or prevent an acquisition or a change in management. These provisions include a classified board of directors, a prohibition on actions by written consent of our stockholders and the ability of the board of directors to issue preferred stock without stockholder approval. In addition, because we are incorporated in Delaware, we are governed by the provisions of Section 203 of the ~~DGCL,~~Delaware General Corporation Law, which prohibits stockholders owning in excess of 15% of our voting stock from merging or combining with us. Although we believe these provisions collectively will provide for an opportunity to receive higher bids by requiring potential acquirers to negotiate with our board of directors, they would apply even if the offer may be considered beneficial by some stockholders. In addition, these provisions may frustrate or prevent any attempts by our stockholders to replace or remove then current management by making it more difficult for stockholders to replace members of the board of directors, which is responsible for appointing the members of management.

We do not anticipate that we will pay any cash dividends in the foreseeable future.

We expect to retain our future earnings to fund the development and growth of our business. As a result, capital appreciation, if any, of our common stock will be the sole source of gain for our stockholders, if any, for the foreseeable future.

Future sales of shares by existing stockholders could cause our stock price to decline.

If existing stockholders sell, or indicate an intention to sell, substantial amounts of our common stock in the public market after legal restrictions on resale lapse, the trading price of our common stock could decline. Certain of our existing stockholders, including Columbia Threadneedle Investments, 683 Capital Management, BlackRock Institutional Trust, and The Vanguard Group, and their respective affiliated entities, own substantial ownership interest in our common stock and any decision to sell a significant number of shares may negatively impact the price of our common stock.

The ownership of our common stock is highly concentrated, and it may prevent stockholders from influencing significant corporate decisions and may result in conflicts of interest that could cause our stock price to decline.

Our executive officers, directors and 5% stockholders and their affiliates beneficially own or control a significant portion of the outstanding shares of our common stock. Accordingly, these executive officers, directors, 5% stockholders and their affiliates, acting as a group, have substantial influence over the outcome of corporate actions requiring stockholder approval, including the election of directors, any merger, consolidation or sale of all or substantially all of our assets or any other significant corporate transactions. These stockholders may also delay or prevent a change of control of us, even if such a change of control would benefit our other stockholders. The significant concentration of stock ownership may adversely affect the trading price of our common stock due to investors’ perception that conflicts of interest may exist or arise.

Our net operating loss carryforwards and certain other tax attributes are now subject to limitations.


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

	~~Page No.~~
		Page No.
PART I. FINANCIAL INFORMATION
Item 1. Financial Statements:			3
Condensed Consolidated Balance Sheets as of March 3 1 , 2023 (unaudited) and December 31, 2022			3
Condensed Consolidated Statements of Operations for the three months ended March 31, 2023 and 2022 (unaudited)			4
Condensed Consolidated Statements of Comprehensive ~~(Loss) Income~~Loss for the three months ended Mar ch 3 1 , 202 3 and 202 2 (unaudited)			5
Condensed Consolidated Statements of Stockholders’ Equity for the three months ended March 31, 2023 and 2022 (unaudited)			6
Condensed Consolidated Statements of Cash Flows for the three months ended March 31, 2023 and 2022 (unaudited)			7
Notes to the Condensed Consolidated Financial Statements (unaudited)			8
Item 2. Management’s Discussion and Analysis of Financial Condition and Results of Operations			19 20
Item 3. Quantitative and Qualitative Disclosures About Market Risk			27
Item 4. Controls and Procedures			27

PART II. OTHER INFORMATION			28
Item 1. Legal Proceedings			28
Item 1A. Risk Factors			28
Item 2. Unregistered Sales of Equity Securities and Use of Proceeds			66 69
Item 3. Defaults Upon Senior Securities			66 69
Item 4. Mine Safety Disclosures			66 69
Item 5. Other Information			66 69
Item 6. Exhibits			67 70
Signatures			68 71

	March 31,			December 31,
	2022			2021				March 31, 2023		December 31, 2022
	(Unaudited)							(Unaudited)
Assets							Assets
Current assets:							Current assets:
Cash and cash equivalents	$	46,562		$	22,221		Cash and cash equivalents	$	15,181	$	25,798
Short-term debt securities		86,155			66,594		Short-term debt securities	60,091		73,150
Accounts receivable, net		2,287			2,576		Accounts receivable, net	3,891		1,749
Inventories		1,910			2,612		Inventories	5,338		2,853
Prepaid expenses and other current assets		10,442			9,361		Prepaid expenses and other current assets	12,410		13,985
Total current assets		147,356			103,364		Total current assets	96,911		117,535
Long-term debt securities		—			17,262
Property and equipment, net		545			613		Property and equipment, net	804		696
Operating lease right-of-use assets		521			653		Operating lease right-of-use assets	446		561
Other assets		4,907			4,510		Other assets	1,067		1,347
Total assets	$	153,329		$	126,402		Total assets	$	99,228	$	120,139
Liabilities and Stockholders’ Equity							Liabilities and Stockholders’ Equity
Current liabilities:							Current liabilities:
Accounts payable	$	9,218		$	7,765		Accounts payable	$	11,858	$	8,975
Accrued liabilities		14,255			13,699		Accrued liabilities	11,706		15,655
Current portion of operating lease liabilities		590			628		Current portion of operating lease liabilities	435		491
Current portion of long-term debt, net		12,549			7,809
Total current liabilities		36,612			29,901		Total current liabilities	23,999		25,121
Long-term debt, net		19,446			23,986
Debt, net of current portion							Debt, net of current portion	39,989		39,625
Operating lease liabilities		4			116		Operating lease liabilities	1		83
Total liabilities		56,062			54,003		Total liabilities	63,989		64,829
Stockholders’ equity:							Stockholders’ equity:
Common stock		41			35		Common stock	44		44
Additional paid-in capital		460,808			412,930		Additional paid-in capital	495,342		492,759
Accumulated other comprehensive loss		(522	)		(149	)	Accumulated other comprehensive loss	(170)		(300)
Accumulated deficit		(363,060	)		(340,417	)	Accumulated deficit	(459,977)		(437,193)
Total stockholders’ equity		97,267			72,399		Total stockholders’ equity	35,239		55,310
Total liabilities and stockholders’ equity	$	153,329		$	126,402		Total liabilities and stockholders’ equity	$	99,228	$	120,139

	Three Months Ended
	March 31,							Three Months Ended March 31,
	2022			2021				2023		2022
Product revenue, net	$	2,673		$	3,646		Product revenue, net	$	4,118	$	2,673
Costs and operating expenses:							Costs and operating expenses:
Cost of sales		110			53		Cost of sales	118		110
Research and development		17,570			13,842		Research and development	16,748		17,570
Selling, general and administrative		6,813			5,564		Selling, general and administrative	9,515		6,813
Total costs and operating expenses		24,493			19,459		Total costs and operating expenses	26,381		24,493
Loss from operations		(21,820	)		(15,813	)	Loss from operations	(22,263)		(21,820)
Interest expense		(886	)		(885	)	Interest expense	(1,285)		(886)
Interest income		45			51		Interest income	711		45
Other income, net		27			45,914
(Loss) income before provision for income taxes		(22,634	)		29,267
Other (expense) income, net							Other (expense) income, net	55		27
Loss before provision for income taxes							Loss before provision for income taxes	(22,782)		(22,634)
Provision for income taxes		9			19		Provision for income taxes	2		9
Net (loss) income	$	(22,643	)	$	29,248
Net (loss) income per common share:
Basic	$	(0.64	)	$	0.86
Diluted	$	(0.64	)	$	0.85
Net loss							Net loss	$	(22,784)	$	(22,643)
Net loss per common share:							Net loss per common share:
Basic and diluted							Basic and diluted	$	(0.52)	$	(0.64)
Weighted-average common shares outstanding:							Weighted-average common shares outstanding:
Basic		35,253,147			33,886,896
Diluted		35,253,147			34,220,895
Basic and diluted							Basic and diluted	44,145,635		35,253,147

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

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

	Common Stock				Additional Paid-In		Accumulated Other Comprehensive			Accumulated			Total Stockholders’
	Shares		Amount		Capital		Loss			Deficit			Equity
Balance at December 31, 2021		34,568,821	$	35	$	412,930	$	(149	)	$	(340,417	)	$	72,399
Issuance of common stock upon offering at-the-market, net of $1,288 of commissions		5,841,786		6		45,604		—			—			45,610
Issuance of common stock upon exercise of stock options		15,995		—		144		—			—			144
Vesting of common stock issued under Product Development Agreement		—		—		19		—			—			19
Issuance of common stock upon ESPP purchase		18,130		—		64		—			—			64
Issuance of common stock upon release of restricted stock units		85,106		—		—		—			—			—
Stock-based compensation expense		—		—		2,047		—			—			2,047
Unrealized loss on available-for-sale debt securities, net		—		—		—		(373	)		—			(373	)
Net loss		—		—		—		—			(22,643	)		(22,643	)
Balance at March 31, 2022		40,529,838	$	41	$	460,808	$	(522	)	$	(363,060	)	$	97,267


	Common Stock			Additional Paid-In Capital		Accumulated Other Comprehensive Loss		Accumulated Deficit		Total Stockholders’ Equity
	Shares	Amount
Balance at December 31, 2021	34,568,821	$	35	$	412,930	$	(149)	$	(340,417)	$	72,399
Issuance of common stock upon offering at-the-market, net of $1,288 of commissions	5,841,786	6		45,604		—		—		45,610
Issuance of common stock upon exercise of stock options	15,995	—		144		—		—		144
Vesting of common stock issued under Product Development Agreement	—	—		19		—		—		19
Issuance of common stock upon ESPP purchase	18,130	—		64		—		—		64
Issuance of common stock upon release of restricted stock units	85,106	—		—		—		—		—
Stock-based compensation expense	—	—		2,047		—		—		2,047
Unrealized loss on available-for-sale debt securities, net	—	—		—		(373)		—		(373)
Net loss	—	—		—		—		(22,643)		(22,643)
Balance at March 31, 2022	40,529,838	$	41	$	460,808	$	(522)	$	(363,060)	$	97,267


	March 31, 2022									March 31, 2023
	Level 1		Level 2		Level 3		Total			Level 1		Level 2		Level 3		Total
Financial assets:									Financial assets:
Money market funds	$	40,483	$	—	$	—	$	40,483	Money market funds	$	12,631	$	—	$	—	$	12,631
Corporate debt securities		—		33,264		—		33,264	Corporate debt securities	—		19,783		—		19,783
Commercial paper		—		10,904		—		10,904	Commercial paper	—		4,990		—		4,990
U.S. government bonds		—		41,987		—		41,987	U.S. government bonds	—		35,318		—		35,318
Total	$	40,483	$	86,155	$	—	$	126,638	Total	$	12,631	$	60,091	$	—	$	72,722


	December 31, 2021									December 31, 2022
	Level 1		Level 2		Level 3		Total			Level 1		Level 2		Level 3		Total
Financial assets:									Financial assets:
Money market funds	$	13,520	$	—	$	—	$	13,520	Money market funds	$	11,546	$	—	$	—	$	11,546
Commercial paper									Commercial paper	—		8,913		—		8,913
Corporate debt securities		—		41,511		—		41,511	Corporate debt securities	—		28,642		—		28,642
U.S. government bonds		—		42,345		—		42,345	U.S. government bonds	—		39,563		—		39,563
Total	$	13,520	$	83,856	$	—	$	97,376	Total	$	11,546	$	77,118	$	—	$	88,664


	March 31, 2022										March 31, 2023
	Amortized cost		Unrealized gain		Unrealized loss			Estimated Fair Value			Amortized cost		Unrealized gain		Unrealized loss		Estimated Fair Value
Cash equivalents:										Cash equivalents:
Money market funds	$	40,483	$	—	$	—		$	40,483	Money market funds	$	12,631	$	—	$	—	$	12,631
Total cash equivalents	$	40,483	$	—	$	—		$	40,483	Total cash equivalents	$	12,631	$	—	$	—	$	12,631
Debt securities:										Debt securities:
Corporate debt securities	$	33,461	$	—	$	(197	)	$	33,264	Corporate debt securities	$	19,820	$	—	$	(37)	$	19,783
Commercial paper		10,904		—		—			10,904	Commercial paper	4,990		—		—		4,990
U.S. government bonds		42,312		—		(325	)		41,987	U.S. government bonds	35,314		8		(4)		35,318
Total debt securities	$	86,677	$	—	$	(522	)	$	86,155	Total debt securities	$	60,124	$	8	$	(41)	$	60,091
Classified as:										Classified as:
Cash equivalents								$	40,483	Cash equivalents							$	12,631
Short-term debt securities									86,155	Short-term debt securities							60,091
								$	126,638								$	72,722


	March 31, 2023		December 31, 2022
Face value of debt	$	40,756	$	40,531
Exit fee	2,600		2,600
Unamortized debt discount associated with exit fee, debt issuance costs and loan origination fees	(3,367)		(3,506)
Total debt, net	$	39,989	$	39,625

	Shares Available for Grant			Number of Options			Weighted- Average Exercise Price		Weighted- Average Remaining Contractual Life (in Years)		Aggregate Intrinsic Value
Outstanding as of December 31, 2021		1,327,645			5,262,185		$	10.24		7.25	$	530
Additional shares authorized		1,728,441			—
Granted		(1,353,300	)		1,353,300		$	5.17
Restricted stock units granted		(298,150	)		—
Exercised		—			(15,995	)	$	8.98
Forfeited or cancelled		109,039			(109,039	)	$	12.06
Restricted stock units forfeited		33,225			—
Outstanding as of March 31, 2022		1,546,900			6,490,451		$	9.16		7.75	$	7,636
Vested and exercisable as of March 31, 2022					3,115,184		$	11.07		6.22	$	1,934


	Three Months Ended March 31,			Three Months Ended March 31,
	2022	2021		2023	2022
Expected term (in years)	5.27-6.08	5.27-6.08	Expected term (in years)	0.86-6.08	5.27-6.08
Volatility	68.71%-70.75%	72.39%-100.87%	Volatility	90.21%-156.25%	68.71%-70.75%
Risk free interest rate	1.76%-2.41%	0.62%-1.16%	Risk free interest rate	3.56%-4.85%	1.76%-2.41%
Dividend yield	—	—	Dividend yield	—	—

~~Delaware~~		~~33-0971591~~


	March 31,		December 31,
	2022		2021			March 31, 2023		December 31, 2022
Raw materials	$	1,056	$	1,056	Raw materials	$	4,290	$	1,703
Work-in-progress		781		1,468	Work-in-progress	834		884
Finished goods		73		88	Finished goods	214		266
Total inventories	$	1,910	$	2,612	Total inventories	$	5,338	$	2,853

	Shares			Weighted- Average Grant Date Fair Value
Unvested shares as of December 31, 2021		623,000		$	8.63
							Shares	Weighted- Average Grant Date Fair Value
Unvested shares as of December 31, 2022						Unvested shares as of December 31, 2022	641,407	$	7.08
Granted		298,150		$	5.22	Granted	54,167	$	2.26
Vested		(85,106	)	$	10.09	Vested	(192,147)	$	5.12
Forfeited		(33,225	)	$	8.33	Forfeited	(13,456)	$	7.44
Unvested shares as of March 31, 2022		802,819		$	7.22
Unvested shares as of March 31, 2023						Unvested shares as of March 31, 2023	489,971	$	7.31


Undiscounted lease payments	March 31, 2022		Undiscounted lease payments	March 31, 2023
Remaining in 2022		501
2023		115
Remaining in 2023			Remaining in 2023	$	375
2024		1	2024	84
2025		1	2025	1
Total undiscounted payments		618	Total undiscounted payments	460
Less: imputed interest		24	Less: imputed interest	24
Present value of future lease payments		594	Present value of future lease payments	436
Less: current portion of operating lease liabilities		590	Less: current portion of operating lease liabilities	435
Operating lease liabilities	$	4	Operating lease liabilities	$	1


	Three Months Ended March 31,						$			%				Three Months Ended March 31,				$ Change
	2022			2021			Change			Change				2023		2022
Product revenue, net	$	2,673		$	3,646		$	(973	)		(27	)%	Product revenue, net	$	4,118	$	2,673			$	1,445			54	%
Total revenue													Total revenue	4,118		2,673		1,445				54	%
Costs and operating expenses:													Costs and operating expenses:
Cost of sales		110			53			57			108	%	Cost of sales	118		110		8				7	%
Research and development		17,570			13,842			3,728			27	%	Research and development	16,748		17,570		(822)				(5)	%
Selling, general and administrative		6,813			5,564			1,249			22	%	Selling, general and administrative	9,515		6,813		2,702				40	%
Total costs and operating expenses		24,493			19,459			5,034			26	%	Total costs and operating expenses	26,381		24,493		1,888				8	%
Loss from operations		(21,820	)		(15,813	)		(6,007	)		38	%	Loss from operations	(22,263)		(21,820)		(443)				2	%
Interest expense		(886	)		(885	)		(1	)		0	%	Interest expense	(1,285)		(886)		(399)				45	%
Interest income		45			51			(6	)		(12	)%	Interest income	711		45		666				*
Other income, net		27			45,914			(45,887	)	*
(Loss) income before provision for income taxes		(22,634	)		29,267			(51,901	)		(177	%)
Other (expense) income, net													Other (expense) income, net	55		27		28				104	%
Loss before provision for income taxes													Loss before provision for income taxes	(22,782)		(22,634)		(148)				1	%
Provision for income taxes		9			19			(10	)		(53	%)	Provision for income taxes	2		9		(7)				(78)	%
Net (loss) income	$	(22,643	)	$	29,248		$	(51,891	)		(177	%)
Net loss													Net loss	$	(22,784)	$	(22,643)	$	(141)			1	%

~~Exhibit~~ ~~Number~~
Exhibit Number						Description of Document

3.1						Amended and Restated Certificate of Incorporation of Celladon Corporation (incorporated by reference to Exhibit 3.1 to the Current Report on Form 8-K of Celladon Corporation, filed with the SEC on February 10, 2014).

3.2						Amended and Restated Bylaws of Celladon Corporation (incorporated by reference to Exhibit 3.2 to the Current Report on Form 8-K, filed with the SEC on February 10, 2014).

3.3						Agreement and Plan of Merger and Reorganization, dated as of November 18, 2015, by and among Celladon Corporation, Celladon Merger Sub, Inc., and Eiger BioPharmaceuticals, Inc. (incorporated by reference to Exhibit 2.1 to the Current Report on Form 8-K filed with the SEC on November 19, 2015).

3.4						Certificate of Amendment of Amended and Restated Certificate of Incorporation of Celladon Corporation (incorporated by reference to Annex D to the Registration Statement on Form S-4, as amended (File No. 333-208521), originally filed with the SEC on December 14, 2015).

~~3.4~~ 3.5						Certificate of Amendment of Amended and Restated Certificate of Incorporation of Celladon Corporation (incorporated by reference to Annex E to the Registration Statement on Form S-4, as amended (File No. 333-208521), originally filed with the SEC on December 14, 2015).

10.1						Separation Agreement and General Rel e ase, dated as of February 6, 2023, by and between Eiger BioPharmaceuticals, Inc. and David A. Cory (incorporated by reference to Exhibit 10.41 to the Annual Report on Form 10-K (File No. 001-36183) filed with the SEC on March 17, 2023).

10.2						Offer Letter Agreement, dated as January 9, 2023, by and between Eiger BioPharmaceuticals, Inc. and David Apelian (incorporated by reference to Exhibit 10.42 to the Annual Report on Form 10-K (File No. 001-36183) filed with the SEC on March 17, 2023).

10.3						Second Amendment to Lease, dated February 16, 2023, by and between Eiger BioPharmaceuticals, Inc. and the McDonald Family Co. LLC. (incorporated by reference to Exhibit 10.43 to the Annual Report on Form 10-K (File No. 001-36183) filed with the SEC on March 17, 2023).

31.1**						Certification of Principal Executive Officer required by Rule 13a-14(a) or Rule 15d-14(a).

31.2**						Certification of Principal Financial Officer required by Rule 13a-14(a) or Rule 15d-14(a).

32.1+						Certifications of Principal Executive Officer and Principal Financial Officer required by Rule 13a-14(b) or Rule 15d-14(b) and Section 1350 of Chapter 63 of Title 18 of the United States Code (18 U.S.C. §1350).

101.INS**						Inline XBRL Instance Document- the instance document does not appear in the Interactive Data File because its XBRL tags are embedded within the Inline XBRL document.

101.SCH**						Inline XBRL Taxonomy Extension Schema Document

101.CAL**						Inline XBRL Taxonomy Extension Calculation Linkbase Document

101.DEF**						Inline XBRL Taxonomy Extension Definition Linkbase Document

101.LAB**						Inline XBRL Taxonomy Extension Label Linkbase Document

101.PRE**						Inline XBRL Taxonomy Extension Presentation Linkbase Document

104						The cover page from the Company’s Quarterly Report on Form 10-Q for the quarter ended March 31, ~~2022,~~2023, has been formatted in Inline XBRL.


	Eiger BioPharmaceuticals, Inc.

Date: May ~~5, 2022~~ 11, 2023	By:	~~By:~~		/s/ David ~~A. Cory~~ Apelian
				David ~~A. Cory~~ Apelian
				Director, ~~President and~~Interim Chief Executive Officer
				(Principal Executive Officer)

			Eiger BioPharmaceuticals, Inc.

Date: May ~~5, 2022~~ 11, 2023	By:	~~By:~~		/s/ ~~Sriram Ryali~~ William G. Kachioff
				~~Sriram Ryali~~ William G. Kachioff
				Chief Financial Officer
				(Principal Financial Officer)

(State or Other Jurisdiction of

Incorporation or Organization)

(I.R.S. Employer

Identification No.)

2155 Park Boulevard
Palo Alto, CA

(Address of Principal Executive Offices)

(Zip Code)