The Company’s business involves various risks and uncertainties in addition to the normal risks of business, some of which are discussed in this section.
−Removed: It should be noted that the Company’s business may be adversely affected by general economic conditions and other forces beyond the Company’s control.
+Added: It should be noted that the Company’s business may be adversely affected by general economic conditions and other factors beyond the Company’s control.
In addition, other risks and uncertainties not presently known or that the Company currently believes to be immaterial may also adversely affect the Company’s business.
+Added: Some of the factors, events, and contingencies discussed below may have occurred in the past, but the disclosures below are not representations as to whether or not the factors, events, or contingencies have occurred in the past, and instead reflect our beliefs and opinions as to the factors, events or contingencies that could materially and adversely affect us in the future.
Any such risks or uncertainties, or any of the following risks or uncertainties, that develop into actual events could result in a material and adverse effect on the Company’s business, financial condition, results of operations, or liquidity.
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• Our prospects substantially depend on the success of our clinical-stage product candidates.
−Removed: If we and our licensees are unable to obtain approval for and commercialize these product candidates, our business could be materially harmed.
−Removed: • There are substantial risks inherent in attempting to commercialize our new drugs, and, as a result, we may not be able to successfully develop products for commercial use.
+Added: If we and our licensees are unable to obtain approval for and commercialize these product candidates, or successfully commercialize REDEMPLO, our business could be materially harmed.
+Added: • There are substantial risks inherent in attempting to commercialize our new drugs, and, as a result, we may not be able to successfully develop additional products for commercial use.
• Our product candidates are in clinical development, which is a lengthy and expensive process with uncertain outcomes and the potential for substantial delays.
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• Our clinical trials may not yield successful results for the product candidates that we may identify and pursue for their intended uses, which would prevent, delay or limit the scope of regulatory approval and commercialization.
−Removed: • Our clinical trials may reveal significant adverse events, toxicities or other side effects and may result in a safety profile that could inhibit regulatory approval or market acceptance of any of our product candidates.
+Added: • Our clinical trials may reveal significant adverse events, toxicities or other side effects and may result in a safety profile that could impede regulatory approval or market acceptance of any of our product candidates.
• Results of earlier studies or clinical trials may not be predictive of future clinical trial results, and initial studies or clinical trials may not establish an adequate safety or efficacy profile for our product candidates to justify proceeding to advanced clinical trials or an application for regulatory approval.
−Removed: • We face potential product liability exposure, and if successful claims are brought against us, we may incur substantial liability for a product candidate and may have to limit its commercialization.
−Removed: • The successful commercialization of our product candidates, if approved, will depend in part on the extent to which government authorities and health insurers establish adequate reimbursement levels and pricing policies.
−Removed: • Our commercialization, collaborative and other arrangements may give rise to disputes over commercial terms, contract interpretation and ownership or protection of our intellectual property and may adversely affect the commercial success of our products.
+Added: • We face potential product liability exposure, and if successful claims are brought against us, we may incur substantial liability from REDEMPLO, or any other approved product candidate, and may have to limit its commercialization.
+Added: • The successful commercialization of REDEMPLO, or any other product candidates, will depend in part on the extent to which government authorities and health insurers establish adequate reimbursement levels and pricing policies.
+Added: • Our commercialization, collaborative and other arrangements may give rise to disputes over commercial terms, contract interpretation, and ownership or protection of our intellectual property and may adversely affect the commercial success of our product candidates.
Risks Related to Regulatory Review and Approval of Our Candidates
−Removed: • A Fast Track product designation may not lead to a faster development or regulatory review or approval process, and it does not increase the likelihood that our product candidates will receive marketing approval.
+Added: • A Fast Track or Breakthrough Therapy product designation may not lead to a faster development or regulatory review or approval process, and it does not increase the likelihood that our product candidates will receive marketing approval.
• We and our licensees conduct clinical trials for product candidates outside the United States, and the FDA and comparable foreign regulatory authorities may not accept data from such trials.
• Even if we obtain FDA approval for products in the United States, we may never obtain approval to commercialize any product candidates outside of the United States, which would limit our ability to realize their full market potential.
−Removed: • Even if our product candidates are approved for commercialization, failure to comply with regulatory requirements or unanticipated problems with our products may result in various adverse actions such as the suspension or withdrawal of one or more of our products, closure of a facility or enforcement of substantial penalties or fines.
+Added: • If the FDA or comparable foreign regulatory authorities approve generic versions of REDEMPLO, or any other potential products that receive marketing approval, or such authorities do not grant REDEMPLO appropriate periods of data or market exclusivity before approving a generic version, the sales of REDEMPLO could be adversely affected.
+Added: • Failure to comply with regulatory requirements or unanticipated problems with our products may result in various adverse actions such as the suspension or withdrawal of one or more of our products, closure of a facility or enforcement of substantial penalties or fines.
• Pharmaceutical and biological product marketing is subject to substantial regulation in the U.S.
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• We are party to technology license agreements with third parties that require us to satisfy obligations to keep them effective and, if these agreements are terminated, our technology and our business could be seriously and adversely affected.
+Added: • We may be and have been subject to patent infringement claims, which could result in substantial costs and liability and prevent us from commercializing our potential products.
Risks Related to Our Business Model
• Our business model assumes we will generate revenue by, among other activities, marketing or out-licensing the products we develop.
−Removed: Our drug candidates are in various stages of development and we have no approved products based on RNA interference and our delivery technologies.
+Added: Our product candidates are in various stages of development and we have only one product based on RNAi and our delivery technologies approved in November 2025.
Accordingly, there is a limited amount of information about us upon which you can evaluate our business and prospects.
−Removed: • We may need to establish additional relationships with strategic and development partners to fully develop our drug candidates and market any approved products.
−Removed: • Our ability to generate milestone and royalty payments under our current and potential future licensing and collaboration agreements is substantially controlled by our partners, and as such, we will likely need other sources of financing to continue to develop our internal drug candidates.
+Added: • We may need to establish additional relationships with strategic and development partners to fully develop our product candidates and market any approved products.
+Added: • Our ability to generate milestone and royalty payments under our current and potential future licensing and collaboration agreements is substantially controlled by our partners, and as such, we will likely need other sources of financing to continue to develop our internal product candidates.
• We may lose a considerable amount of control over our intellectual property and may not receive anticipated revenues in strategic transactions, particularly where the consideration is contingent on the achievement of development or sales milestones.
−Removed: • We will need to achieve commercial acceptance of our drug candidates to generate revenues and achieve profitability .
−Removed: • If the market opportunities for our approved product candidates, if any, are smaller than we expect, it could materially adversely affect our financial condition and results of operations.
−Removed: • We have limited manufacturing capability and must rely on third-party manufacturers to manufacture our clinical supplies and commercial products, if and when approved, and if they fail to meet their obligations, the development and commercialization of our products could be adversely affected.
+Added: • We will need to achieve commercial acceptance of REDEMPLO and our other product candidates to generate revenues and achieve profitability .
+Added: • If the market opportunities for REDEMPLO, or any other approved product candidates, are smaller than we expect, it could materially and adversely affect our financial condition and results of operations.
+Added: • We have limited manufacturing capability and capacity and must rely on third-party manufacturers to manufacture certain of our clinical supplies and our commercial products, if and when approved, and if they fail to meet their obligations, the development and commercialization of our products could be adversely affected.
• We rely on third parties to conduct our clinical trials, and if they fail to fulfill their obligations, the development of our products may be adversely affected.
−Removed: • We face competition from various entities including large pharmaceutical companies, small biotech companies, private companies, and research institutions.
• We may have difficulty expanding our operations successfully as we evolve our pipeline and move toward commercializing drugs.
• Because we use biological materials, hazardous materials, chemicals and radioactive compounds, if we do not comply with laws regulating the protection of the environment and health and human safety, our business could be adversely affected.
−Removed: • Our operations, including our relationships with healthcare providers, physicians and third-party payers, are subject to applicable anti-kickback, fraud and abuse, and other healthcare laws and regulations, which, in the event of a violation, exposes us to liability for criminal sanctions, civil penalties, and contractual damages, and reputational harm and diminished profits and future earnings.
+Added: • Our operations, including our relationships with healthcare providers, physicians, and third-party payers are subject to applicable anti-kickback, fraud and abuse, and other healthcare laws and regulations, which, in the event of a violation, exposes us to liability for criminal sanctions, civil penalties, contractual damages, and reputational harm and diminished profits and future earnings.
• The actions of distributors and specialty pharmacies could affect our ability to sell or market products profitably.
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If we are unable to comply with restrictions in our Sixth Street Financing Agreement, the repayment of our existing indebtedness could be accelerated.
−Removed: • If the estimates we make, or the assumptions on which we rely, in preparing our consolidated financial statements prove inaccurate, our actual results may vary from those reflected in our accruals.
• Our operating results may fluctuate significantly, which makes our future operating results difficult to predict and could cause our operating results to fall below expectations or our guidance.
−Removed: • The investment of our cash, cash equivalents and fixed income securities is subject to risks which may cause losses and affect the liquidity of these investments.
• Our ability to utilize net operating loss carryforwards and other tax benefits may be limited.
Risks Related to Investment and Securities
−Removed: • If securities or industry analysts do not publish research reports about our business or if they make adverse recommendations regarding an investment in our stock, our stock price and trading volume may decline.
• The market for purchases and sales of our common stock may be limited, and the sale of a limited number of shares could cause the price to fall sharply.
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• Drug development is time consuming, expensive and risky.
−Removed: • Regulatory standards are subject to change over time, making it difficult to accurately predict the likelihood of marketing approval even when clinical trials meet their endpoints.
+Added: • Evolving regulatory standards make it difficult to accurately predict the likelihood of marketing approval even when clinical trials meet their endpoints.
Risks Related to Our Discovery, Development, and Commercialization of Medicines
Our prospects substantially depend on the success of our clinical-stage product candidates.
−Removed: If we and our licensees are unable to obtain approval for and commercialize these product candidates, our business could be materially harmed.
−Removed: Our future success is substantially dependent on the ability of our company and our licensees to timely complete clinical trials and obtain marketing approval for, and then successfully commercialize our clinical-stage product candidates.
+Added: If we and our licensees are unable to obtain approval for and commercialize these product candidates, or successfully commercialize REDEMPLO, our business could be materially harmed.
+Added: Our future success is substantially dependent on the ability of the Company and our licensees to timely complete clinical trials and obtain marketing approval for, and then successfully commercialize our clinical-stage product candidates.
We are not permitted to market or promote our product candidates before we receive marketing approval from the FDA and comparable foreign regulatory authorities, and we may never receive such marketing approvals.
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• obtaining positive data that supports demonstration of efficacy, safety and tolerability profiles and durability of effect for our product candidates that are satisfactory to the FDA or any comparable foreign regulatory authority for marketing approval;
+Added: • successful inspections by FDA or any comparable foreign regulatory authority of our manufacturing facilities and clinical trial sites, including as part of the review process for marketing approval;
• successful and timely enrollment of appropriate patients for the indications included in our current and future clinical trials;
• potential variability of patient outcomes;
−Removed: • the extent of any required post-marketing approval commitments to applicable regulatory authorities;
+Added: • the extent of any required post-marketing approval commitments, potentially including post-marketing clinical trials or other studies, to applicable regulatory authorities;
• the establishment of and maintenance of sufficient internal manufacturing capabilities;
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• a continued acceptable safety profile following any marketing approval;
−Removed: • commercial acceptance by patients, the medical community and third-party payors;
+Added: • commercial acceptance by patients, the medical community and third-party payers;
• our ability to compete with other therapies.
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If we do not receive marketing approvals for such product candidates, we may not be able to continue our operations.
−Removed: There are substantial risks inherent in attempting to commercialize our new drugs, and, as a result, we may not be able to successfully develop products for commercial use.
−Removed: Scientific research and development requires significant amounts of capital and takes a long time to reach commercial viability if it can be achieved at all.
−Removed: To date, our research and development projects have not produced
−Removed: commercially viable drugs and may never do so.
+Added: There are substantial risks inherent in attempting to commercialize our new drugs, and, as a result, we may not be able to successfully develop additional products for commercial use.
+Added: Scientific research and development requires significant amounts of capital and even approved drug candidates take a long time to reach commercial viability if it can be achieved at all.
During the research and development process, we may experience technological barriers that we may be unable to overcome.
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For instance, ARO-RAGE has demonstrated the ability to reduce the expression of RAGE in the lung, however it has not been established that this will have an anti-inflammatory effect sufficient for a meaningful clinical benefit in patients with inflammatory lung disease.
−Removed: Further, it is also unknown at this time what may be required to gain favorable reimbursement .
−Removed: With respect to fazirsiran, it is also unknown at this time what changes in the liver may be required to gain regulatory approval and/or favorable reimbursement for a drug that reduces the production of mutant alpha-1 antitrypsin in the liver.
+Added: Further, it is also unknown at this time what may be required to gain adequate reimbursement by either commercial or government payers .
+Added: With respect to fazirsiran, it is also unknown at this time what changes in the liver may be required to gain regulatory approval and/or adequate reimbursement for a drug that reduces the production of mutant alpha-1 antitrypsin in the liver.
Similar uncertainties and risks exist that are specific to each of our development programs.
−Removed: Because of these and similar uncertainties, it is possible that no commercial products will be successfully developed.
If we are unable to successfully develop commercial products, we will be unable to generate revenue or build a sustainable or profitable business.
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The process of completing clinical testing and obtaining required approvals will take several years and require the use of substantial resources.
−Removed: For instance, we currently plan to study plozasiran in a cardiovascular outcomes trial, and cardiovascular outcomes trials are expensive clinical trials performed in a large number of subjects over several years.
Further, there can be no assurance that product candidates employing a new technology will be shown to be safe and effective in clinical trials or receive applicable regulatory approvals.
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We cannot be certain that current clinical trials or any future clinical trials, whether conducted by us or our licensees, will be successful.
−Removed: Additionally, any safety concerns observed in any one of our clinical trials in our targeted indications could limit the prospects for regulatory approval of our product candidates in those and other indications, which could have
−Removed: a material adverse effect on our business, financial condition and results of operation.
+Added: Additionally, any safety concerns observed in any one of our clinical trials in our targeted indications could limit the prospects for regulatory approval of our product candidates in those and other indications, which could have a material adverse effect on our business, financial condition and results of operation.
Success in clinical trials in a particular indication does not ensure that a product candidate will be successful in other indications.
Similarly, approval of a product candidate in a particular indication does not ensure that the product candidate will be successful in other indications.
−Removed: For instance, although plozasiran ’ s Phase 3 PALISADE trial for patients with FCS was successful in achieving its primary endpoint and all multiplicity-controlled key secondary endpoints, and we filed an NDA with the FDA on November 16, 2024 and sought regulatory approval with additional global regulatory authorities thereafter, there can be no guarantee that the FDA or another regulatory authority approves plozasiran for the treatment of FCS, and plozasiran may not succeed in achieving its clinical trial endpoints or be approved for the treatment of larger indications such as sHTG or ASCVD because the endpoints and clinical data required for approval in a rare disease indication are different from what is required for a broader patient population.
+Added: For instance, although REDEMPLO ’ s Phase 3 PALISADE trial for patients with FCS was successful in achieving its primary endpoint and all multiplicity-controlled key secondary endpoints, and we have filed for regulatory approval with global regulatory authorities, there can be no guarantee that global regulatory authorities that have not already approved REDEMPLO for the treatment of FCS will do so, and REDEMPLO may not succeed in achieving its clinical trial endpoints or be approved for the treatment of larger indications such as sHTG because the endpoints and clinical data required for approval in a rare disease indication are different from what is required for a broader patient population.
Moreover, results acceptable to support approval in one jurisdiction may be deemed inadequate by another regulatory authority to support regulatory approval in that other jurisdiction.
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Such safety concerns have led to labeling changes, restrictions on distribution through use of a REMS, or withdrawal of products from the market, and any of our product candidates may be subject to similar risks.
−Removed: Although to date our current drug candidates have generally evidenced an acceptable safety profile in clinical trials, patients treated with our products, if approved, may experience previously unreported adverse reactions or minor incidences of adverse reactions may manifest with greater frequency in subsequent larger trials, and it is possible that the FDA or other regulatory authorities may ask for additional safety data as a condition of, or in connection with, our efforts to obtain approval of our product candidates.
−Removed: If toxicities, adverse events or any other safety problems occur or are identified after our products, if any, reach the market, we may make the decision or be required by regulatory authorities to
−Removed: conduct additional clinical safety trials, amend the labeling of our products or add additional warnings to the labeling, recall our products, or even withdraw approval for our products.
+Added: Although to date our current product candidates have generally evidenced an acceptable safety profile in clinical trials, patients treated with REDEMPLO or any of our product candidates, if approved, may experience previously unreported adverse reactions or minor incidences of adverse reactions may manifest with greater frequency in subsequent larger trials, and it is possible that the FDA or other regulatory authorities may ask for additional safety data as a condition of, or in connection with, our efforts to obtain approval of our product candidates.
+Added: If toxicities, adverse events or any other
+Added: safety problems occur or are identified after our products reach the market, we may make the decision or be required by regulatory authorities to conduct additional clinical safety trials, amend the labeling of our products or add additional warnings to the labeling, recall our products, or even withdraw approval for our products.
Topline data may not accurately reflect the complete results of a particular study or trial.
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As a result, topline data should be viewed with caution until the final data are available.
−Removed: Further, others, including regulatory agencies, may not accept or agree with our assumptions, estimations, calculations, conclusions or analyses or may interpret or weigh the importance of data differently, which could impact the value of the particular program, the approvability or commercialization of the particular drug candidate or drug and our company in general.
+Added: Further, others, including regulatory agencies, may not accept or agree with our assumptions, estimations, calculations, conclusions or analyses or may interpret or weigh the importance of data differently, which could impact the value of the particular program, the approvability or commercialization of the particular drug candidate or drug and the Company in general.
In addition, the information we may publicly disclose regarding a particular study or clinical trial is based on what is typically extensive information, and you or others may not agree with what we determine is the material or otherwise appropriate information to include in our disclosure, and any information we determine not to disclose may ultimately be deemed significant with respect to future decisions, conclusions, views, activities or otherwise regarding a particular drug, drug candidate or our business.
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We may not commence or complete clinical trials involving any of our product candidates as projected or may not conduct them successfully.
−Removed: We face potential product liability exposure, and if successful claims are brought against us, we may incur substantial liability for a product candidate and may have to limit its commercialization.
−Removed: The use of our product candidates in clinical trials and the sale of any products for which we obtain marketing approval expose us to the risk of product liability claims.
+Added: We face potential product liability exposure, and if successful claims are brought against us, we may incur substantial liability from REDEMPLO, or any other approved product candidate, and may have to limit its commercialization.
+Added: The use of our product candidates in clinical trials and the sale of REDEMPLO, or any other products for which we obtain marketing approval expose us to the risk of product liability claims.
Product liability claims might be brought against us by clinical trial participants, consumers, healthcare providers, pharmaceutical companies, or others selling our products.
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Moreover, insurance coverage is becoming increasingly expensive and, in the future, we may not be able to maintain insurance coverage at a reasonable cost or in sufficient amounts to protect us against losses.
−Removed: The successful commercialization of our product candidates, if approved, will depend in part on the extent to which government authorities and health insurers establish adequate reimbursement levels and pricing policies.
−Removed: Sales of any approved drug candidate will depend in part on the availability of coverage and reimbursement from third-party payers such as government insurance programs, including Medicare and Medicaid, private health insurers, health maintenance organizations and other health care related organizations, who are increasingly challenging the price of medical products and services.
+Added: The successful commercialization of REDEMPLO, or any other approved product candidates, will depend in part on the extent to which government authorities and health insurers establish adequate reimbursement levels and pricing policies.
+Added: Sales of REDEMPLO, or any other approved drug candidate, will depend in part on the availability of coverage and reimbursement from third-party payers such as government insurance programs, including Medicare and Medicaid, private health insurers, health maintenance organizations and other health care related organizations, who are increasingly challenging the price of medical products and services.
Accordingly, coverage and reimbursement may be uncertain.
Adoption of any drug by the medical community may be limited if third-party payers will not offer adequate coverage.
−Removed: Additionally, significant uncertainty exists as to the reimbursement status of newly-approved drugs.
+Added: Additionally, significant uncertainty exists as to the reimbursement status of newly-approved drugs, including REDEMPLO.
Cost control initiatives may decrease coverage and payment levels for any drug and, in turn, the price that we will be able to charge and/or the volume of our sales.
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Any denial of private or government payer coverage or inadequate reimbursement could harm our business and reduce our revenue.
−Removed: With respect to our partnered product candidates, we will be reliant on that partner to obtain reimbursement from government and private payors for the drug, if approved, and any failure of that partner to establish adequate reimbursement could have a negative impact on our revenues and profitability.
+Added: With respect to our partnered product candidates, we will be reliant on that partner to obtain reimbursement from government and private payers for the drug, if approved, and any failure of that partner to establish adequate reimbursement could have a negative impact on our revenues and profitability.
In addition, both the federal and state governments in the United States and foreign governments continue to propose and pass new legislation, regulations, and policies affecting coverage and reimbursement rates, which are designed to contain or reduce the cost of health care.
Further federal and state proposals and healthcare reforms are likely, which could limit the prices that can be charged for the product candidates that we develop and may further limit our commercial opportunity.
−Removed: For example, the IRA includes several measures intended to lower the cost of prescription drugs and related healthcare reforms, including limits on price increases and subjecting an escalating number of drugs to annual price negotiations with CMS (The Centers for Medicare & Medicaid Services).
−Removed: We cannot be sure whether additional legislation or rulemaking related to the IRA will be issued or enacted, or what impact, if any, such changes will have on the profitability of any of our drug candidates, if approved for commercial use, in the future.
−Removed: There also may be future changes unrelated to the IRA that result in reductions in potential coverage and reimbursement levels for our product candidates, if approved and commercialized, and we cannot predict the scope of any future changes or the impact that those changes would have on our operations.
+Added: For example, the IRA includes several measures intended to lower the cost of prescription drugs and related healthcare reforms, including limits on price increases and subjecting an escalating number of drugs to annual price negotiations with the Centers for Medicare & Medicaid Services ("CMS").
+Added: In addition, an executive order issued by the White House on May 12, 2025, directs the Department of Health and Human Services (the “HHS”) to implement a “Most Favored Nation” drug pricing policy.
+Added: See also “ The healthcare system is under significant financial pressure to reduce costs, which could reduce payment and reimbursement rates for drugs.
+Added: ” And the recently-enacted One Big Beautiful Bill Act (the “OBBBA”) imposes new restrictions on funding for government health care programs and on individual eligibility for coverage under those programs, which may lead to lower reimbursements for drugs covered by those programs.
+Added: We cannot be sure whether additional legislation or rulemaking related to these developments will be issued or enacted, or what impact, if any, such changes will have on the profitability of any of our drug candidates, if approved for commercial use, in the future.
+Added: There also may be future changes unrelated to these that result in reductions in potential coverage and reimbursement levels for our product candidates, if approved and commercialized, and we cannot predict the scope of any future changes or the impact that those changes would have on our operations.
If future reimbursement for approved product candidates, if any, is substantially less than we project, or rebate obligations associated with them are substantially greater than we expect, our future net revenue and profitability could be materially diminished.
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Although we may obtain orphan designations in the treatment of certain diseases our products are intended to treat, the designation may not be applicable to any particular product we might get approved and that product may not be the first product to receive approval for that indication.
−Removed: Under the Orphan Drug Act, the first product with an orphan designation receives market exclusivity, which prohibits the FDA from approving the “same” drug for the same indication.
+Added: Under the Orphan Drug Act, the first approved product with an orphan designation receives market exclusivity, which prohibits the FDA from approving the “same” drug for the same indication.
The FDA has stated that drugs can be the “same” even when they are not identical but has not provided guidance with respect to how it will determine “sameness” for RNAi drugs.
−Removed: It is possible that another RNAi drug could be approved for the treatment of a disease that one of our orphan products is intended to treat before our product is approved, which means that we may not
−Removed: obtain orphan drug exclusivity and could also potentially be blocked from approval until the first product’s orphan drug exclusivity period expires or we demonstrate, if we can, that our product is superior.
+Added: It is possible that another RNAi drug could be approved for the treatment of a disease that one of our orphan products is intended to treat before our product is approved, which means that we may not obtain orphan drug exclusivity and could also potentially be blocked from approval until the first product’s orphan drug exclusivity period expires or we demonstrate, if we can, that our product is superior.
Further, even if we obtain orphan drug exclusivity for a product, that exclusivity may not effectively protect the product from competition because different drugs can be approved for the same condition.
Even after an orphan drug is approved and granted orphan drug exclusivity, the FDA can subsequently approve the same drug for the same condition if the FDA concludes that the later drug is safer, more effective or makes a major contribution to patient care.
+Added: In addition, a designated Orphan Drug may not receive orphan drug exclusivity if it is approved for a use that is broader than the disease for which it received orphan designation.
+Added: Recent court decisions have created uncertainty in the application and interpretation of orphan drug exclusivity.
Further, orphan drug exclusivity can be lost if the FDA later determines that the request for designation was materially defective or if the applicant is unable to assure the availability of sufficient quantities of the drug to meet the needs of patients with the disease or condition for which the drug was designated.
+Added: Orphan Drug designation neither shortens the development time or regulatory review time of a drug nor gives the drug any advantage in the regulatory review or approval process.
Our success depends on the attraction and retention of senior management and scientists with relevant expertise.
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Risks Related to Regulatory Review and Approval of Our Product Candidates
−Removed: Breakthrough Therapy designation for Plozasiran and/or Fazirsiran (formerly ARO-AAT) may not lead to a faster development or review process.
−Removed: We have been granted a Breakthrough Therapy designation for plozasiran in the United States for the treatment of FCS and fazirsiran in the United States for the treatment of liver disease associated with AATD.
+Added: Breakthrough Therapy designation for Fazirsiran (formerly ARO-AAT) and other of our current or future product candidates and other of our current or future product candidates may not lead to a faster development or review process.
+Added: We have been granted a Breakthrough Therapy designation for fazirsiran in the United States for the treatment of liver disease associated with AATD, and we may seek Breakthrough Therapy designation for other current or future product candidates.
Breakthrough Therapy designation is intended to facilitate the development and expedite the review of new therapies to treat serious conditions with unmet medical needs by providing sponsors with the opportunity for frequent interactions and additional drug development guidance with the FDA and its senior managers.
−Removed: Breakthrough Therapy designation applies to the combination of the drug candidate and the specific indication for which it is being studied.
+Added: Breakthrough Therapy designation applies to the combination of the product candidate and the specific indication for which it is being studied.
Product candidates that receive Breakthrough Therapy designation may receive more frequent interactions with the FDA regarding the product candidate’s development plan and clinical trials and may be eligible for the FDA’s Rolling Review.
−Removed: Despite receiving Breakthrough Therapy designation, plozasiran and/or fazirsiran may not actually benefit from faster clinical development or regulatory review or approval any sooner than other product candidates that do not have such designation, or at all.
−Removed: Furthermore, such a designation does not increase the likelihood that plozasiran or fazirsiran will receive marketing approval in the United States.
−Removed: The FDA may also rescind Breakthrough Therapy designation if it determines that plozasiran or fazirsiran no longer meets the relevant criteria.
+Added: Despite receiving Breakthrough Therapy designation, fazirsiran or other product candidates may not actually benefit from faster clinical development or regulatory review or approval any sooner than other product candidates that do not have such designation, or at all.
+Added: For example, although we received Breakthrough Therapy designation for REDEMPLO in the United States for the treatment of FCS, REDEMPLO was ultimately reviewed on a standard timeline.
+Added: Furthermore, such a designation does not increase the likelihood that fazirsiran or other product candidates will receive marketing approval in the United States.
+Added: The FDA may also rescind Breakthrough Therapy designation if it determines that fazirsiran or other product candidates no longer meets the relevant criteria.
A Fast Track product designation may not lead to faster development or regulatory review or approval process, and it does not increase the likelihood that our product candidates will receive marketing approval.
−Removed: We have received a Fast Track product designation for plozasiran in the United States for the treatment of FCS, and we may seek Fast Track designation for other of our current or future product candidates.
+Added: We have received a Fast Track product designation for fazirsiran in the United States for the treatment of liver disease associated with AATD, and we may seek Fast Track designation for other of our current or future product candidates.
The Fast Track designation is a program offered by the FDA designed to facilitate drug development and to expedite the review of new drugs that are intended to treat serious or life-threatening conditions.
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The receipt of such a designation for a product candidate may not result in a faster development process, review, or approval compared to drugs considered for approval under conventional FDA procedures and does not assure ultimate marketing approval by the FDA.
+Added: For example, although we received Fast Track designation for REDEMPLO in the United States for the treatment of FCS, REDEMPLO was ultimately reviewed on a standard timeline.
In addition, the FDA may later decide that the products no longer meet the designation conditions.
+Added: We may seek priority review designation for one or more of our product candidates, but we might not receive such designation, and even if we do, such designation may not lead to faster development or regulatory review or approval process.
+Added: If the FDA determines that a product candidate offers a treatment for a serious condition and, if approved, the product would provide a significant improvement in safety or effectiveness, the FDA may designate the product candidate for priority review.
+Added: A priority review designation means that the goal for the FDA to review an application is six months from the filing date, rather than the standard review period of ten months.
+Added: We may request priority review for our product candidates.
+Added: The FDA has broad discretion with respect to whether or not to grant priority review status to a product candidate, so even if we believe a particular product candidate is eligible for such designation or status, the FDA may decide not to grant it.
+Added: Moreover, a priority review designation does not necessarily mean a faster development or regulatory review or approval process or necessarily confer any advantage with respect to approval compared to conventional FDA procedures.
+Added: Receiving priority review from the FDA does not guarantee approval within the six-month review cycle or at all.
We intend to deliver some of our product candidates via drug delivery devices that will have their own regulatory, development, supply and other risks.
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Even if approval is obtained for our products, we may also be dependent on those third-party companies continuing to maintain such approvals or clearances, if required, for their drug delivery devices once they have been received.
−Removed: Failure of third-party companies to supply the devices, to successfully complete studies on the devices in a timely manner, or to obtain or maintain required approvals or clearances of the devices could result in increased development costs, delays in or failure to obtain regulatory
−Removed: approval and delays in product candidates reaching the market or in gaining approval or clearance for expanded labels for new indications.
+Added: Failure of third-party companies to supply the devices, to successfully complete studies on the devices in a timely manner, or to obtain or maintain required approvals or clearances of the devices could result in increased development costs, delays in or failure to obtain regulatory approval and delays in product candidates reaching the market or in gaining approval or clearance for expanded labels for new indications.
We and our licensees con duct clinical trials for product candidates outside the United States, and the FDA and comparable foreign regulatory authorities may not accept data from such trials.
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There can be no assurance that the FDA or any comparable foreign regulatory authority will accept data from trials conducted outside of the United States or the applicable jurisdiction.
−Removed: Most of our clinical trials involve study subjects outside of the United States , including most of our phase 1 clinical trials (which often enroll study subjects in Australia and New Zealand), and our Phase 3 clinical trials of plozasiran, for which we have enrolled (with respect to FCS and sHTG) and plan to enroll (with respect to ASCVD) cohorts outside the United States.
+Added: Most of our clinical trials involve study subjects outside of the United States , including most of our Phase 1 clinical trials (which often enroll study subjects in Australia and New Zealand), and our Phase 3 clinical trials of plozasiran and zodasiran, for which we have enrolled and plan to enroll cohorts outside the United States.
If the FDA or any comparable foreign regulatory authority does not accept such data, it would result in the need for additional trials, which would be costly and time-consuming and delay aspects of our business plan, and which may result in product candidates that we may develop not receiving approval or clearance for commercialization in the applicable jurisdiction.
Even if we obtain FDA approval for products in the United States, we may never obtain approval to commercialize any product candidates outside of the United States, which would limit our ability to realize their full market potential.
−Removed: In order to market any products outside of the United States, we must establish and comply with numerous and varying regulatory requirements of other countries regarding safety and effectiveness.
+Added: In order to market any products outside of the United States, we must establish and comply with numerous and varying regulatory requirements of other countries regarding safety and effectiveness, and the chemistry, manufacturing and controls for the product.
Clinical trials conducted in one country may not be accepted by regulatory authorities in other countries, and regulatory approval in one country does not mean that regulatory approval will be obtained in any other country.
−Removed: Approval processes vary among countries and can involve additional product testing and validation and additional or different administrative review periods from those in the United States, including additional preclinical studies or clinical trials.
+Added: Approval processes and requirements vary among countries and can involve additional product testing and validation and additional or different administrative review periods from those in the United States, including additional preclinical studies or clinical trials.
In many jurisdictions outside the United States, a product candidate must be approved for reimbursement before it can be approved for sale in that jurisdiction.
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If we fail to comply with regulatory requirements in international markets or to obtain and maintain required approvals, or if regulatory approval in international markets is delayed, our target market will be reduced and our ability to realize the full market potential of our products will be harmed.
−Removed: Even if our product candidates are approved for commercialization, failure to comply with regulatory requirements or unanticipated problems with our products may result in various adverse actions such as the suspension or withdrawal of one or more of our products, closure of a facility or enforcement of substantial penalties or fines.
−Removed: If regulatory approval to sell any of our product candidates is received, regulatory agencies will subject any marketed product(s) and the facilities where they are manufactured to continual review and periodic inspection.
−Removed: If previously unknown problems with a product, manufacturing and laboratory facilities or regulatory requirements are discovered, such as adverse events of unanticipated severity or frequency, problems with a manufacturing process or laboratory facility, or failure to comply with applicable regulatory approval requirements, a regulatory agency may impose restrictions or penalties on that product or on us.
+Added: If the FDA or comparable foreign regulatory authorities approve generic versions of REDEMPLO, or any other potential products that receive marketing approval, or such authorities do not grant REDEMPLO appropriate periods of data or market exclusivity before approving a generic version, the sales of REDEMPLO could be adversely affected.
+Added: Once an NDA is approved, the drug covered thereby becomes a “reference-listed drug” in the FDA’s publication, “Approved Drug Products with Therapeutic Equivalence Evaluations.” Manufacturers may seek marketing approval of generic versions of reference-listed drugs through submission of ANDAs in the United States.
+Added: Generic drugs may be significantly less costly to bring to market than the reference-listed drug and companies that produce generic drugs are generally able to offer them at lower prices.
+Added: Thus, following the introduction of a generic drug, a significant percentage of the sales of any branded product or reference-listed drug is typically lost to the generic drug.
+Added: The FDA may not approve an ANDA or a 505(b)(2) NDA for a generic drug until any applicable period of non-patent exclusivity for the reference-listed drug has expired.
+Added: The FDCA provides a period of five years of non-patent exclusivity for a new drug containing a new chemical entity.
+Added: During the exclusivity period, the FDA may not accept for review an ANDA or a 505(b)(2) NDA submitted by another company for another version of such product candidate where the applicant does not own or have a legal right of reference to all the data required for approval.
+Added: However, an application may be submitted after four years if it contains a certification of patent invalidity or non-infringement.
+Added: The FDCA also provides three years of marketing exclusivity for an NDA, 505(b)(2) NDA or supplement to an approved NDA if new clinical investigations, other than bioavailability studies, that were conducted or sponsored by the applicant are deemed by the FDA to be essential to the approval of the application, for example, for new indications, dosages or strengths of an existing product candidate.
+Added: This three-year exclusivity covers only the conditions associated with the new clinical investigations and does not prohibit the FDA from approving ANDAs for product candidates containing the original active agent for other conditions of use.
+Added: Five-year and three-year exclusivity will not delay the submission or approval of a full NDA.
+Added: However, an applicant submitting a full NDA would be required to conduct or obtain a right of reference to all of the nonclinical studies and adequate and well-controlled clinical trials necessary to demonstrate safety and effectiveness.
+Added: Manufacturers may seek to launch generic drugs following the expiration of the marketing exclusivity period, even if we still have patent protection for such drugs.
+Added: Competition that REDEMPLO, or any other potential product candidates, may face from generic drugs could materially and adversely impact our future revenue, profitability and cash flows and substantially limit our ability to obtain a return on the investments we have made in those products.
+Added: Our future revenues, profitability and cash flows could also be materially and adversely affected and our ability to obtain a return on the investments we have made in REDEMPLO or other product candidates may be substantially limited if REDEMPLO, or any other potential products, product candidates, are not afforded the appropriate periods of non-patent exclusivity.
+Added: Failure to comply with regulatory requirements or unanticipated problems with our products may result in various adverse actions such as the suspension or withdrawal of one or more of our products, closure of a facility or enforcement of substantial penalties or fines.
+Added: Regulatory agencies subject any marketed product(s), such as REDEMPLO, and the facilities where they are manufactured to continual review and periodic inspection.
+Added: If previously unknown problems with a product, manufacturing and laboratory facilities or regulatory requirements are discovered, such as AEs of unanticipated severity or frequency,
+Added: problems with a manufacturing process or laboratory facility, or failure to comply with applicable regulatory approval requirements, a regulatory agency may impose restrictions or penalties on that product or on us.
Such restrictions or penalties may include, among other things:
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and any failure by us or our commercial and collaborative partners to comply with applicable statutes or regulations can adversely affect our business.
−Removed: Any marketing activities associated with our product candidates, if approved for commercialization , will be subject to numerous federal and state laws governing the marketing and promotion of pharmaceutical and biological products.
+Added: Any marketing activities associated with REDEMPLO, or any other product candidates approved for commercialization , will be subject to numerous federal and state laws governing the marketing and promotion of pharmaceutical and biological products.
The FDA regulates post-approval promotional labeling and advertising to ensure that they conform to statutory and regulatory requirements.
In addition to FDA restrictions, the marketing of prescription drugs is subject to laws and regulations prohibiting fraud and abuse under government healthcare programs.
−Removed: Similarly, many states have similar statutes or regulations that apply to items and services reimbursed under Medicaid and other state programs, and, in some states, such statutes or regulations apply regardless of the payor.
+Added: Similarly, many states have similar statutes or regulations that apply to items and services reimbursed under Medicaid and other state programs, and, in some states, such statutes or regulations apply regardless of the payer.
In addition, government authorities may also seek to hold us responsible for any failure of our commercialization or collaborative partners to comply with applicable statutes or regulations.
−Removed: If we, or our commercial or collaborative partners, fail to comply with applicable FDA regulations or other laws or regulations relating to the marketing of our product candidates, if approved for commercialization, we could be subject to criminal prosecution, civil penalties, seizure of products, injunctions and exclusion of our product candidates from reimbursement under government programs, as well as other regulatory or investigatory actions against our future product candidates, our commercial or collaborative partners or us.
+Added: If we, or our commercial or collaborative partners, fail to comply with applicable FDA regulations or other laws or regulations relating to the marketing of REDEMPLO, or any other approved product candidates, we could be subject to criminal prosecution, civil penalties, seizure of products, injunctions and exclusion of our product candidates from reimbursement under government programs, as well as other regulatory or investigatory actions against our future product candidates, our commercial or collaborative partners or us.
See also “ Our operations, including our relationships with healthcare providers, physicians and third-party payers, are subject to applicable anti-kickback, fraud and abuse, and other healthcare laws and regulations, which, in the event of a violation, exposes us to liability for criminal sanctions, civil penalties, and contractual damages, and reputational harm and diminished profits and future earnings.
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Such patent applications may not be available for licensing or may not be economically feasible to license.
−Removed: Certain of our patents may not be granted or may not contain claims of the necessary breadth because, for example, prior patents exist.
+Added: Certain of our patents may not be granted or may not contain claims of the necessary breadth because, for example, prior patents or publications exist.
If a particular patent is not granted, the value of the invention described in the patent would be diminished.
Further, even if these patents are granted, they may be difficult to enforce.
−Removed: Even if ultimately successful, efforts to enforce our patent rights could be expensive, distracting for management, cause our patents to be invalidated or held unenforceable, and thus frustrate commercialization of products.
−Removed: Even if patents are issued and are enforceable, others may develop similar, superior or parallel technologies to any technology developed by us and not infringe on our patents.
−Removed: Our technology may prove to infringe upon patents or rights owned by others.
Patent prosecution and maintenance is expensive, and we may be forced to curtail prosecution or maintenance if our cash resources are limited.
Thus, the patents held by or licensed to us may not afford us any meaningful competitive advantage.
−Removed: In addition, the laws of some foreign countries in which we do business, including through our joint ventures, do not protect intellectual property rights to the same extent or in the same manner as the laws of the United States.
+Added: Even if ultimately successful in obtaining patent protection, efforts to enforce our patent rights could be expensive, distracting for management, cause our patents to be invalidated or held unenforceable, and thus frustrate commercialization of products.
+Added: Even if patents are issued and are enforceable, others may develop similar, superior or parallel technologies to any technology developed by us and not infringe on our patents.
+Added: Additionally, our technology may be accused of infringing and may ultimately prove to infringe upon patents or rights owned by others.
+Added: The Company may be subject to intellectual property litigation that could negatively impact our ability to commercialize REDEMPLO and our product candidates, if approved.
+Added: For example, on September 10, 2025, the Company filed a Complaint for Declaratory Judgment in the United States District Court for the District of Delaware against Ionis Pharmaceuticals, Inc.
+Added: (“Ionis”) to declare that the United States Patent No.
+Added: 9,593,333 (“the ’333 patent”) is invalid and not infringed by the Company’s planned commercialization of investigational plozasiran, and on September 11, 2025, Ionis filed a Complaint for Patent Infringement against the Company in the United States District Court for the Central District of California alleging patent infringement of the ’333 patent.
+Added: In addition, the laws of some foreign countries in which we do business, including through our joint ventures, do not protect intellectual property rights to the same extent or in the
+Added: same manner as the laws of the United States.
Moreover, if we or our licensors fail to maintain the patents and patent applications covering our product candidates or technologies, including as a result of geopolitical events such as civil or political unrest (including the ongoing conflicts between Ukraine and Russia and Israel and Palestine), we may not be able to use such patents and patent applications or stop a competitor from marketing products that are the same as or similar to our product candidates.
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Additionally, the USPTO and patent offices in other jurisdictions have often required that patent applications directed to pharmaceutical and/or biotechnology-related inventions be limited or narrowed substantially to cover only the specific innovations exemplified in the patent application, thereby limiting the scope of protection against competitive challenges.
−Removed: Accordingly, even if we or our
−Removed: licensors are able to obtain patents, the patents might be substantially narrower than anticipated.
+Added: Accordingly, even if we or our licensors are able to obtain patents, the patents might be substantially narrower than anticipated.
Thus, there is no assurance as to the degree and range of protections any of our patents, if issued, may afford us or whether patents will be issues.
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If we fail to satisfy our obligations under these agreements, the terms of the licenses may be materially modified, such as by rendering currently exclusive licenses non-exclusive, or may give our licensors the right to terminate their respective agreement with us, which could limit our ability to implement our current business plan and harm our business and financial condition.
−Removed: We may be subject to patent infringement claims, which could result in substantial costs and liability and prevent us from commercializing our potential products.
+Added: We may be and have been subject to patent infringement claims, which could result in substantial costs and liability and prevent us from commercializing our potential products.
Because the intellectual property landscape in the fields in which we participate is rapidly evolving and interdisciplinary, it is difficult to conclusively assess our freedom to operate without infringing on third-party rights.
−Removed: However, if granted marketing approval, we are currently aware of certain patent rights held by third parties that, if found to be valid and enforceable, could be alleged to render one or more of our drug candidates infringing.
−Removed: If a claim should be brought and is successful, we may be required to pay substantial damages, be forced to abandon any affected drug candidates and/or seek a license from the patent holder.
−Removed: In addition, any patent infringement claims brought against us, whether or not successful, may cause us to incur significant expenses and divert the attention of our management and key personnel from other business concerns.
+Added: However, if granted marketing approval, we are currently aware of certain patent rights held by third parties that, if found to be valid and enforceable, could be alleged to render one or more of our drug products or candidates infringing.
+Added: For example, a s t he Company previously reported in Form 8-K filed on September 12, 2025, Ionis Pharmaceuticals, Inc.
+Added: (“Ionis”) filed a complaint for patent infringement against the Company in the United States District Court for the Central District of California alleging patent infringement of United States Patent No.
+Added: 9,593,333 (“the ’333 patent”) (the "Ionis Claim"), which may impact our planned commercialization of REDEMPLO .
+Added: See also “ Our ability to protect our patents and other proprietary rights is uncertain, exposing us to the possible loss of competitive advantage.” If the Ionis Claim or any potential future claim by another party is successful, we may be required to pay substantial damages, be forced to abandon any affected drug product and/or product candidates and/or seek a license from the patent holder.
+Added: In addition, the Ionis Claim and any future patent infringement claims brought against us, whether or not successful, may cause us to incur significant expenses and divert the attention of our management and key personnel from other business concerns.
These could negatively affect our results of operations and prospects.
We cannot be certain that patents owned or licensed by us will not be challenged, potentially successfully, by others.
−Removed: In addition, if our product candidates are found to infringe the intellectual property rights of third parties, these third parties may assert infringement claims against our customers, licensees and other parties with whom we have business relationships, and we may be required to indemnify those parties for any damages they suffer as a result of these claims.
+Added: In addition, if our products and/or product candidates are found to infringe the intellectual property rights of third parties, these third parties may assert infringement claims against our customers, licensees and other parties with whom we have business relationships, and we may be required to indemnify those parties for any damages they suffer as a result of these claims.
The claims may require us to initiate or defend protracted and costly litigation on behalf of customers, licensees, and other parties regardless of the merits of these claims.
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In these countries, the patent owner may have limited remedies, which could materially diminish the value of such patent.
−Removed: If we or any of our licensors is forced to grant a license to third parties with respect to any patents relevant to our business, our competitive position may be impaired, and our business, financial condition, results of operations and prospects may be adversely affected.
+Added: If we or any of our licensors are forced to grant a license to third parties with respect to any patents relevant to our business, our competitive position may be impaired, and our business, financial condition, results of operations and prospects may be adversely affected.
The intellectual property systems in other countries can be destabilized or unpredictable as a result of geopolitical events such as civil or political unrest (including the ongoing conflicts between Ukraine and Russia and Israel and Palestine).
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Our business model assumes we will generate revenue by, among other activities, marketing or out-licensing the products we deve lop.
−Removed: Our drug candidates are in various stages of development and we have no approved products based on RNA interference and our delivery technologies.
+Added: Our product candidates are in various stages of development and we currently have only one product based on RNAi and our delivery technologies which was approved in November 2025.
Accordingly, there is a limited amount of information about us upon which you can evalua te our business and prospects.
−Removed: We have no approved drugs and thus have not begun to market or generate revenues from the commercialization of any product candidates.
−Removed: Because no drug candidates generated with our product platform have been approved, we have not yet demonstrated an ability to successfully overcome many of the risks and uncertainties frequently encountered by companies in new and rapidly evolving fields, particularly in the biopharmaceutical area.
+Added: We have not begun to generate revenues from the commercialization of REDEMPLO or any product candidates.
+Added: As such, we have not yet demonstrated an ability to successfully overcome many of the risks and uncertainties frequently encountered by companies in new and rapidly evolving fields, particularly in the biopharmaceutical area.
For example, to execute our business plan, we will need to successfully:
−Removed: • Execute product development activities using technologies that have not yet generated an approved product;
+Added: • execute product development activities using technologies that have not yet generated revenues;
• build, maintain, and protect a strong intellectual property portfolio;
−Removed: • Demonstrate safety and efficacy of our drug candidates in multiple human clinical studies;
+Added: • demonstrate safety and efficacy of our product candidates in multiple human clinical studies;
• receive FDA approval and approval from similar foreign regulatory bodies;
• gain market acceptance for the development and commercialization of any drugs we develop;
−Removed: • Ensure our products are reimbursed by commercial and/or government payors at a rate that permits commercial viability;
+Added: • ensure our products are reimbursed by commercial and/or government payers at a rate that permits commercial viability;
• develop and maintain successful strategic relationships with suppliers, distributors, and commercial licensing partners;
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If we are unsuccessful in accomplishing these objectives, we may not be able to develop products, raise capital, expand our business or continue our operations.
−Removed: We may need to establish additional relationships with strategic and development partners to fully develop our drug candidates and market any approved products.
−Removed: Over the past several years we have entered into license and collaboration agreements with Takeda, Janssen, Amgen, Horizon, GSK and Visirna.
−Removed: Our business strategy includes securing additional collaborations with other pharmaceutical and biotech companies to support the development of our RNAi therapeutics and other drug candidates.
+Added: We may need to establish additional relationships with strategic and development partners to fully develop our product candidates and market any approved products.
+Added: Over the past several years we have entered into license and collaboration agreements with Takeda, Janssen, Amgen, Horizon, GSK, Sarepta, Visirna and Novartis Pharma AG (“Novartis”).
+Added: Our business strategy includes securing additional collaborations with other pharmaceutical and biotech companies to support the development of our RNAi therapeutics and other product candidates.
We do not possess all of the financial and development resources necessary to develop and commercialize all of the products that may result from our technologies.
−Removed: Unless we expand our own product development capacity and enhance our own internal marketing capability, we may need to make arrangements with other strategic partners to develop and commercialize any drug candidates that may be approved.
+Added: Unless we expand our own product development capacity and enhance our own internal marketing capability, we may need to make arrangements with other strategic partners to develop and commercialize any product candidates that may be approved.
We may not be able to attract such partners, and even if we are able to enter into such partnerships, the terms may be less favorable than anticipated.
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If we do not find appropriate partners, or if our existing arrangements or future agreements are not successful, our ability to develop and commercialize products could be adversely affected.
−Removed: Even if we are able to find collaborative partners, the overall success of the development and commercialization of product candidates in those programs will depend largely on the efforts of other parties and will be beyond our control, particularly as partnered programs progress and our licensees may elect to assume greater control over these programs.
+Added: Even if we are able to find collaborative partners, the overall success of the development and commercialization of product candidates in those programs will depend largely on the efforts of other parties and will be beyond our control, particularly
+Added: as partnered programs progress and our licensees may elect to assume greater control over these programs.
In addition, in the event we pursue our commercialization strategy through collaboration or licenses to third parties, there are a variety of technical, business and legal risks, including:
−Removed: • We may not be able to control the amount and timing of resources that our collaborators may be willing or able to devote to the development or commercialization of our drug candidates or to their marketing and distribution;
−Removed: • Disputes may arise between us and our collaborators that result in the delay or termination of the research, development or commercialization of our drug candidates or that result in costly litigation or arbitration that diverts our management’s resources.
+Added: • we may not be able to control the amount and timing of resources that our collaborators may be willing or able to devote to the development or commercialization of our product candidates or to their marketing and distribution;
+Added: • disputes may arise between us and our collaborators that result in the delay or termination of the research, development or commercialization of our product candidates or that result in costly litigation or arbitration that diverts our management’s resources.
The occurrence of any of the above events or other related events could impair our ability to generate revenues and harm our business and financial condition.
−Removed: Our ability to generate milestone and royalty payments under our current and potential future licensing and collaboration agreements is substantially controlled by our partners, and as such, we will likely need other sources of financing to continue to develop our internal drug candidates.
−Removed: Under our licensing and collaboration agreements with Amgen, Takeda, GSK and Visirna, our partners substantially control clinical development and commercialization for all of the candidates covered under those agreements in their relevant territories.
+Added: Our ability to generate milestone and royalty payments under our current and potential future licensing and collaboration agreements is substantially controlled by our partners, and as such, we will likely need other sources of financing to continue to develop our internal product candidates.
+Added: Under our licensing and collaboration agreements with Amgen, Takeda, GSK, Sarepta, Visirna, Sanofi, and Novartis, our partners substantially control clinical development and commercialization for all of the candidates covered under those agreements in their relevant territories.
To the extent that (i) our partners’ interests in advancing these candidates or targets changes, (ii) unforeseen scientific issues with the candidates arise, or (iii) the pace at which our partners move the candidates through clinical trials toward commercialization slows, our ability to collect milestones and royalties may be significantly diminished.
−Removed: This would further cause us to rely upon other sources of financing to continue to develop our other internal drug candidates.
+Added: This would further cause us to rely upon other sources of financing to continue to develop our other internal product candidates.
We may lose a considerable amount of control over our intellectual property and may not receive anticipated revenues in strategic transactions, particularly where the consideration is contingent on the achievement of development or sales milestones.
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If the acquirers of our technologies fail to achieve performance milestones, we may not receive a significant portion of the total value of any sale, license or other strategic transaction.
−Removed: We will need to achieve commercial acceptance of our drug candidates to generate revenues and achieve profitability.
+Added: We will need to achieve commercial acceptance of REDEMPLO and our product candidates to generate revenues and achieve profitability.
Even if our research and development efforts yield technologically feasible applications, we may not successfully develop commercial products.
−Removed: Drug development takes years of study in human clinical trials prior to regulatory approval, and, even if we are successful in getting regulatory approval of our drug candidates, it may not be on a timely basis.
−Removed: During our drug development period, superior competitive technologies may be introduced which could diminish or extinguish the potential commercial uses for our drug candidates.
+Added: Drug development takes years of study in human clinical trials prior to regulatory approval, and, even if we are successful in getting regulatory approval of our product candidates, it may not be on a timely basis.
+Added: During our drug development period, superior competitive technologies may be introduced which could diminish or extinguish the potential commercial uses for our product candidates.
Additionally, the degree to which the medical community and consumers will adopt any product we develop is uncertain.
−Removed: The rate and degree of market acceptance of our products will depend on a number of factors, including the establishment and demonstration in the medical community of the clinical efficacy and safety of our products, their potential advantage over alternative treatments, and the costs to patients and third-party payors, including insurance companies and Medicare.
+Added: The rate and degree of market acceptance of our products will depend on a number of factors, including the establishment and demonstration in the medical community of the clinical efficacy and safety of our products, their potential advantage over alternative treatments, and the costs to patients and third-party payers, including commercial insurance companies and government health care programs.
Recent efforts in the United States and abroad to reduce overall healthcare spending has put significant pressure on the price of prescription drugs and certain companies have been publicly criticized for the relatively high cost of their therapies.
These pressures may force us to sell any approved drugs at a lower price than we or analysts may anticipate or may result in lower levels of reimbursement and coverage from third parties.
−Removed: Moreover, a s no drug candidates generated with our product platform has been approved for commercialization, we have not generated any revenue from product sales.
−Removed: Our ability to generate significant revenue and achieve profitability depends on our ability, alone or with potential strategic collaboration partners, to complete the development of and obtain the regulatory and marketing approvals necessary to commercialize our drug candidates and introduce products that will be accepted by the medical community .
−Removed: The commercial success of our products, if approved, will depend on many factors, including, but not limited to:
−Removed: • the availability of coverage and adequate and timely reimbursement from managed care plans, private insurers, government payors (such as Medicare and Medicaid and similar foreign authorities) and other third-party payors for our products ;
−Removed: • patients’ ability and willingness to pay out-of-pocket for our products in the absence of coverage and/or adequate reimbursement from third-party payors;
+Added: Moreover , we have not yet generated any revenue from product sales.
+Added: Our ability to generate significant revenue and achieve profitability depends on our ability, alone or with potential strategic collaboration partners, to complete the development of and obtain the regulatory and marketing approvals necessary to commercialize our product candidates and introduce products that will be accepted by the medical community .
+Added: The commercial success of REDEMPLO or any of our product candidates, if approved, will depend on many factors, including, but not limited to:
+Added: • the availability of coverage and adequate and timely reimbursement from managed care plans, private insurers, government payers (such as Medicare and Medicaid and similar foreign authorities) and other third-party payers for our products ;
+Added: • patients’ ability and willingness to pay out-of-pocket for our products in the absence of coverage and/or adequate reimbursement from third-party payers;
• patient demand for our products ;
+Added: • the overall health benefits and costs savings that patients derive from REDEMPLO;
• our ability to establish and enforce intellectual property rights in and to our products ;
• our ability to avoid third-party patent interference, intellectual property challenges or intellectual property infringement claims.
−Removed: We cannot predict whether significant commercial market acceptance for our products, if approved, will ever develop, and we cannot reliably estimate the projected size of any such potential market.
+Added: We cannot predict whether significant commercial market acceptance for REDEMPLO or any of our products, if approved, will ever develop, and we cannot reliably estimate the projected size of any such potential market.
Our revenue growth and achievement of consistent profitability will depend substantially on our ability to introduce products that will be accepted by the medical community.
If we are unable to cost-effectively achieve acceptance of our technology among the medical establishment and patients, or if the associated products do not achieve wide market acceptance, our business will be materially and adversely affected.
−Removed: If the market opportunities for our approved product candidates, if any, are smaller than we expect, it could materially adversely affect our financial condition and results of operation.
−Removed: If the market opportunity for our products, if approved, is smaller than we expect, we may never become or remain profitable nor generate sufficient revenue growth to sustain our business even if we obtain significant market share for them.
+Added: If the market opportunities for REDEMPLO or any other approved product candidates, are smaller than we expect, it could materially adversely affect our financial condition and results of operation.
+Added: If the market opportunity for REDEMPLO or any other approved products, is smaller than we expect, we may never become or remain profitable nor generate sufficient revenue growth to sustain our business even if we obtain significant market share for them.
The potentially addressable patient population for our products may be limited or may not be amenable to treatment with our products, and new patients may become increasingly difficult to identify or access, which would adversely affect our results of operations and our business.
We rely on outside sources for various components and processes for our products.
−Removed: We rely on third parties for various components and processes for our product candidates.
+Added: We rely on third parties for various components and processes for REDEMPLO and our product candidates.
We may not be able to achieve multiple sourcing because there may be no acceptable second source, other companies may choose not to work with us, or the component or process sought may be so new that a second source does not exist or does not exist on acceptable terms.
−Removed: For instance, many of our pulmonary drug candidates are administered using a proprietary delivery device which can only be sourced from a single manufacturer.
+Added: For instance, drug substance and drug product for REDEMPLO are each currently sourced from a single, third-party manufacturer, and many of our pulmonary product candidates are administered using a proprietary delivery device which is currently sourced from a single manufacturer.
There may be a disruption or delay in the performance of our third-party contractors, suppliers or collaborators which is beyond our control.
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Although we have developed our own internal manufacturing capabilities which allow us to manufacture oligonucleotide drug substance for our clinical product candidates, we do not currently have internal manufacturing capabilities beyond such clinical-stage oligonucleotide drug substance.
−Removed: We rely, and expect to continue to rely, on third-party manufacturers for the production of our drug product candidates for clinical trials and potential future commercialization.
+Added: We rely, and expect to continue to rely, on third-party manufacturers for the production of REDEMPLO and our drug product candidates for clinical trials and commercialization.
We may choose to utilize third-party manufacturers to produce some or all of our development candidates, even if we have internal manufacturing capabilities to do so.
Further, we have not developed the ability to manufacture drug product ourselves, nor have we developed the capabilities to manufacture biologics.
−Removed: If we were to experience an unexpected loss or interruption of supply for any of our product candidates, whether as a result of manufacturing, supply or storage issues or otherwise, we could experience delays, disruptions, suspensions or terminations of, or be required to restart or repeat, any pending or ongoing clinical trials.
−Removed: Further, our drug candidates are composed of multiple components and require specific formulations for which scale-up and manufacturing could be difficult.
+Added: If we were to experience an unexpected loss or interruption of supply for REDEMPLO or any of our product candidates, whether as a result of manufacturing, supply or storage issues or otherwise, we could experience disruptions in our commercial sales or delays, disruptions, suspensions or terminations of, or be required to restart or repeat, any pending or ongoing clinical trials.
+Added: Further, our product candidates are composed of multiple components and require specific formulations for which scale-up and manufacturing could be difficult.
For certain products, we have limited experience in such scale-up and manufacturing which may require us to depend on a limited number of third parties, who may not be able to deliver in a timely manner, or at all.
In order to develop products, apply for regulatory approvals, and commercialize our products, we will need to develop, contract for, or otherwise arrange for the necessary manufacturing capabilities.
−Removed: We anticipate an increase in our GMP drug substance manufacturing capacity following the successful completion and integration of our manufacturing facility in Verona, Wisconsin.
+Added: We have increased our GMP drug substance manufacturing capacity following the substantially completed build out and integration of our manufacturing facility in Verona, Wisconsin.
There are a limited number of manufacturers that supply synthetic oligonucleotides.
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Included in these risks are synthesis and purification failures and contamination during the manufacturing process, which could result in unusable product and cause delays in our development process, as well as additional expense to us.
−Removed: Additionally, if any of our product candidates become approved for commercial sale, we will need to establish either internal or third-party manufacturing and analytic capacity.
−Removed: For example, while we are still seeking regulatory approval, we intend to enter into third-party agreements for the manufacturing of plozasiran, in anticipation of a commercial launch in 2025.
+Added: Additionally, as more of our product candidates become approved for commercial sale, we will need to establish either internal or third-party manufacturing and analytical capacity.
+Added: For example, we have entered into third-party agreements for the manufacturing of REDEMPLO for drug substance and drug product, in conjunction with its commercial launch in 2025.
Further, some manufacturing partners may require us to fund capital improvements, perhaps on behalf of third parties, to support the scale-up of manufacturing and related activities.
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If we or any of these manufacturers is unable or unwilling to increase its manufacturing capacity or if we are unable to establish alternative arrangements on a timely basis or on acceptable terms, the development and commercialization of such an approved product may be delayed or there may be a shortage in supply.
−Removed: Any inability to
−Removed: manufacture our product candidates or future approved drugs in sufficient quantities when needed would seriously harm our business.
−Removed: While we are exploring alternative suppliers for certain critical materials, there can be no assurance that our efforts will be successful.
−Removed: If any of our drug candidates is approved by a regulatory authority, manufacturers of our approved products (including us, if we chose to internally manufacture) must comply with cGMP requirements relating to methods, facilities and controls used in the manufacturing, processing and packaging of the product, which are intended to ensure that drug products are safe and that they consistently meet applicable requirements and specifications.
+Added: Any inability to manufacture our product candidates or future approved drugs in sufficient quantities when needed would seriously harm our business.
+Added: While we are exploring alternative suppliers for certain critical materials, some of which are sole sourced, and there can be no assurance that our efforts will be successful.
+Added: Accordingly, there is a risk that supplies of our products and product candidates may be significantly delayed by, or may become unavailable as a result of manufacturing, equipment, process, regulatory or business-related issues affecting that company.
+Added: Manufacturers of our approved products (including us, if we chose to internally manufacture) must comply with cGMP requirements relating to methods, facilities and controls used in the manufacturing, processing and packaging of the product, which are intended to ensure that drug products are safe and that they consistently meet applicable requirements and specifications.
These requirements include quality control, quality assurance, and the maintenance of records and documentation.
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We face competition from various entities including large pharmaceutical companies, small biotech companies, private companies, and research institutions.
−Removed: Many of our competitors have greater financial resources and may have more experience in research and development, manufacturing, managing clinical trials and/or regulatory compliance than we do.
+Added: Many of our competitors have greater financial resources and may have more experience in research and development, manufacturing, managing clinical trials, commercialization and/or regulatory compliance than we do.
Our competitors may compete with us for lead clinical trial investigators, clinical trial site locations and patient enrollment.
−Removed: These competitors may also compete with us on recruiting scientific and management personnel.
−Removed: Because our products are in vario us stages of preclinical and clinical development, along with many of the competing products, and given unpredictability inherent in drug development, it is difficult to predict which third parties may provide the most competition, and on what specific basis that competition may be based.
+Added: These competitors may also compete with us in recruiting scientific and management personnel.
+Added: Because our products are in vario us stages of preclinical and clinical development, along with many of the competing products, and given unpredictability inherent in drug development, it is difficult to predict which third party may be our most direct competitor, and on what factors that competition may be focused.
+Added: Moreover, we also face increased competition from other companies that are using artificial intelligence, some of whom may be able to more quickly and effectively identify and develop novel product candidates compared to us and our business partners, which could impair our ability to compete effectively and have a material adverse effect on our business, results of operations or financial condition.
We may have difficulty expanding our operations successfully as we evolve our pipeline and move toward commercializing drugs.
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This expected growth may place a strain on our administrative and operational infrastructure and information technology systems.
−Removed: As product candidates we develop enter and advance through clinical trials, we will need to expand our development, regulatory, manufacturing, marketing, and sales capabilities or contract with other organizations to provide these capabilities for us.
−Removed: We are currently establishing a sales and marketing infrastructure, and although we have hired individuals with significant experience in the sales, marketing, or distribution of pharmaceutical products, we have never done so as a company.
−Removed: To achieve commercial success for any approved product for which we retain sales and marketing rights, we must continue to develop a sales and marketing organization or outsource these functions to third parties.
−Removed: If we or our collaborators are unable to establish sales, marketing and distribution capabilities or enter into or maintain agreements with third parties to market and sell our product candidates, we may not be successful in commercializing our product candidates if and when they are approved.
+Added: As product candidates we develop enter and advance through clinical trials, we will need to expand our development, regulatory, manufacturing, marketing, sales, and customer support capabilities or contract with other organizations to provide these capabilities for us.
+Added: We are currently establishing a sales, customer support, and marketing infrastructure for REDEMPLO and certain of our product candidates, and although we have hired individuals with significant experience in the sales, customer support, marketing, and distribution of pharmaceutical products, the Company does not have prior experience in commercialization of a product.
+Added: To achieve commercial success for REDEMPLO or any approved product for which we retain sales and marketing rights, we must continue to develop a sales and marketing organization or outsource these functions to third parties.
+Added: If we or our collaborators are unable to establish sales, marketing, customer support, and distribution capabilities or successfully enter into or maintain agreements with third parties to market and sell our products, we may not be successful in commercializing our products.
Further, as our operations expand due to our development progress, we expect that we will need to manage additional relationships with various collaborators, suppliers, and other organizations.
−Removed: Our ability to manage our operations and future growth will
−Removed: require us to continue to improve our operational, financial, information technology and management controls, reporting systems and procedures.
+Added: Our ability to manage our operations and future growth will require us to continue to improve our operational, financial, information technology and management controls, reporting systems and procedures.
We may not be able to effectively manage the expansion of our operations or implement improvements to our management information and control systems in an efficient or timely manner and may discover deficiencies in existing systems and controls.
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Additionally, sensitive data could be leaked, disclosed, or revealed as a result of or in connection with our employees’, personnel’s, vendors’ or partners’ use of generative AI technologies.
−Removed: To the extent that any disruption or cybersecurity incident were to result in a loss of or damage to our data, or inappropriate disclosure of confidential, proprietary or private information, we could incur liability or regulatory penalties, including under laws and regulations governing the protection of protected health information and other personal data, we could lose valuable trade secret rights, the development of our product candidates could be delayed, and we could suffer reputational damage and damage to key business relationships.
+Added: To the extent that any disruption or cybersecurity incident were to result in a loss of or damage to our data, or inappropriate disclosure of confidential, proprietary or private information, we could incur liability or regulatory penalties, including under laws and regulations governing the protection of protected health information and other personal data, we could be subject to litigation (including class-action claims), we could lose valuable trade secret rights, the development of our product candidates could be delayed, and we could suffer reputational damage and damage to key business relationships.
The risk of a cybersecurity incident or other informational technology disruption, particularly through cyber-attacks, has generally increased as the number, intensity and sophistication of attempted attacks and intrusions from around the world have increased.
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If our losses exceed our insurance coverage, our financial condition would be affected.
−Removed: Litigation claims may result in financial losses or harm our reputation and may divert management resources.
+Added: Securities litigation claims may result in financial losses or harm our reputation and may divert management resources.
When the market price of a stock is volatile, holders of that stock have often initiated securities class action litigation against the company that issued the stock.
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Our operations, including any arrangements that we enter into with healthcare providers, physicians, and third-party payers, are subject to broadly applicable fraud and abuse and other healthcare laws and regulations.
−Removed: Such laws and
−Removed: regulations, including applicable U.S.
−Removed: federal and state healthcare laws and regulations, as well as foreign laws, such as the federal Anti-Kickback Statute, the False Claims Act, the Health Insurance Portability and Accountability Act of 1996, or the Foreign Corrupt Practices Act, may constrain our operation and the business or financial arrangements through which we can market, sell and distribute any drug candidates for which we obtain marketing approval.
+Added: Such laws and regulations, including applicable U.S.
+Added: federal and state healthcare laws and regulations, as well as foreign laws, such as the federal Anti-Kickback Statute, the False Claims Act, the Health Insurance Portability and Accountability Act of 1996, or the Foreign Corrupt Practices Act, may constrain our operation and the business or financial arrangements through which we can market, sell and distribute any product candidates for which we obtain marketing approval.
Efforts to confirm that our business arrangements with third parties comply with applicable healthcare laws and regulations involve substantial costs.
It is possible that governmental authorities will conclude that our business practices may not comply with current or future statutes, regulations or case law involving applicable fraud and abuse or other healthcare laws and regulations.
−Removed: If our operations are found to be in violation of any of these laws or any other governmental regulations that may apply to us, we may become subject to significant civil, criminal and administrative penalties, damages, fines, imprisonment, exclusion of products from government funded healthcare programs, such as Medicare and Medicaid, and the curtailment or restructuring of our operations.
+Added: If our operations are found to be in violation of any of these laws or any other governmental regulations that may apply to us, we may become subject to significant civil, criminal and administrative penalties, damages, fines, imprisonment, exclusion of products from government funded healthcare programs, such as Medicare and Medicaid, and the curtailment or restructuring of our operations, and compliance and reporting obligations that could adversely affect our revenues, financial condition or results of operations.
If any of the physicians or other healthcare providers or entities with whom we expect to do business are found to be not in compliance with applicable laws, they may be subject to criminal, civil or administrative sanctions, including exclusions from government funded healthcare programs.
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Fluctuations in buying or distribution patterns by such distributors and specialty pharmacies could adversely affect our revenues, financial condition, or results of operations.
−Removed: We have an exclusive agreement with Vanscoy Rare Pharmacy for drug delivery services, and we expect to rely on this pharmacy for a considerable portion of our sales for plozasiran, if approved.
+Added: We have an exclusive agreement with Vanscoy Rare Pharmacy for drug delivery services, and we expect to rely on this pharmacy for a considerable portion of our sales for REDEMPLO .
The financial failure of Vanscoy Rare Pharmacy could adversely affect our revenues, financial condition or results of operations.
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We have a history of net losses, and we expect to continue to incur net losses and may not achieve or maintain profitability.
−Removed: We have incurred net losses since our inception and we expect that our operating losses will continue for the foreseeable future as we continue our drug development efforts and prepare for the potential commercialization of our product candidates.
−Removed: To achieve profitability, we must, either directly or through licensing and/or partnering relationships, meet certain milestones, successfully develop and obtain regulatory approval for one or more drug candidates and effectively manufacture, market and sell any drugs we successfully develop.
−Removed: Even if we successfully commercialize drug candidates that receive regulatory approval, we may not be able to realize revenues at a level that would allow us to achieve or sustain profitability.
+Added: We have incurred net losses since our inception and we expect that our operating losses will continue for the foreseeable future as we continue our drug development efforts and begin commercialization of our product candidates.
+Added: To achieve profitability, we must, either directly or through licensing and/or partnering relationships, meet certain milestones, successfully develop and obtain regulatory approval for drug candidates and effectively manufacture, market and sell any drugs we successfully develop.
+Added: Even if we successfully commercialize product candidates that receive regulatory approval, we may not be able to realize revenues at a level that would allow us to achieve or sustain profitability.
Accordingly, we may never generate significant revenue and, even if we do generate significant revenue, we may never achieve consistent profitability.
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Our business currently does not generate the cash that is necessary to finance our operations.
−Removed: Subject to the success of the research and development programs of our Company and our partners, and potential licensing or partnering transactions, we may need to raise additional capital to:
−Removed: • Fund research and development infrastructure and activities relating to the development of our drug candidates, including preclinical and clinical trials and manufacturing to support these efforts;
−Removed: • Fund a commercialization infrastructure and activities related to the sale, marketing, customer support, and distribution of our drug products if and when they become approved;
+Added: Subject to the success of the research and development programs of the Company and our partners, and potential licensing or partnering transactions, we may need to raise additional capital to:
+Added: • fund research and development infrastructure and activities relating to the development of our product candidates, including preclinical and clinical trials and manufacturing to support these efforts;
+Added: • fund a commercialization infrastructure and activities related to the sale, marketing, customer support, and distribution of our drug products ;
• fund our general and administrative infrastructure and activities;
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• the extent to which our research and development and clinical efforts are successful;
−Removed: • Expenditures to build out or contract for sales, marketing and distribution capabilities as we prepare for the potential commercialization of our product candidates, if any;
+Added: • expenditures to build out or contract for sales, marketing and distribution capabilities ;
• the outcome of potential partnering or licensing transactions, if any, and the extent to which our business development efforts result in the acquisition of new programs or technologies;
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• our intellectual property positions, if any, in our products;
−Removed: • The regulatory approval process and regulatory standards for our drug candidates.
+Added: • the regulatory approval process and regulatory standards for our product candidates.
We will need to raise additional funds through public or private equity offerings, debt financings or additional strategic alliances and licensing arrangements in the future to continue our operations.
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In addition, as a condition to providing additional funds to us, future investors may demand, and may be granted, rights superior to those of existing stockholders.
−Removed: Debt financing, if available, may involve restrictive covenants that could limit our flexibility in conducting future business activities and, in the event of insolvency, would be paid before holders of equity securities received any distribution of corporate assets.
−Removed: In order to raise additional funds through alliance, joint venture or licensing arrangements, we may be required to relinquish rights to our technologies or drug candidates or grant licenses on terms that are not favorable to us.
+Added: Debt financing, if available, may involve restrictive covenants that could limit our flexibility in conducting future business activities and, in the event of insolvency, would be paid before holders of equity securities receive any distribution of corporate assets.
+Added: In order to raise additional funds through partnerships, joint ventures or licensing arrangements, we may be required to relinquish rights to our technologies or product candidates or grant licenses on terms that are not favorable to us.
If adequate funds are not available, we may have to further delay, reduce or eliminate one or more of our planned activities.
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On August 7, 2024, we entered into a financing agreement with Sixth Street Lending Partners, as the administrative agent and collateral agent for several lenders.
−Removed: The financing agreement establishes a senior secured term loan facility of $500.0 million (the “Credit Facility”), consisting of $400.0 million funded on the closing date and an additional $100.0 million available at the our option, subject to mutual agreement with Sixth Street, over the seven-year term.
−Removed: We have incurred a substantial amount of debt under the financing agreement which could adversely affect our business.
+Added: The financing agreement establishes a senior secured term loan facility of $500.0 million (the “Credit Facility”), consisting of $400.0 million funded on the closing date and an additional $100.0 million available at our option, subject to mutual agreement with Sixth Street, over a seven-year term.
+Added: On November 26, 2024, the Company entered into an amendment to the Financing Agreement to modify, amongst other things, some of the prepayment terms of the loans under the Credit Facility, including the prepayment terms related to the Sarepta Collaboration Agreement.
The financing agreement requires us to make certain payments over time and contains several other negative covenants that, subject to certain exceptions, restrict indebtedness, liens, investments (including acquisitions), fundamental changes, asset sales and licensing transactions, dividends, modifications to material agreements, payment of subordinated indebtedness, and other matters customarily restricted in such agreements.
Among other requirements of the financing agreement, we and our subsidiaries party to the financing agreement must maintain certain liquidity thresholds based on our market capitalization.
−Removed: We are also subject to restrictions on sales and licensing transactions with respect to our core intellectual property and product assets, including, but not limited to, olpasiran, plozasiran, zodasiran, fazirsiran, GSK4532990, and daplusiran/tomligisiran, subject to certain exceptions.
+Added: We are also subject to restrictions on sales and licensing transactions with respect to our core intellectual property and product assets, including, but not limited to, olpasiran, REDEMPLO , zodasiran, fazirsiran,
+Added: GSK4532990, and daplusiran/tomligisiran, subject to certain exceptions.
These and other terms in the financing agreement could restrict our ability to grow our business or enter into transactions that we believe would be beneficial to our business.
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Our business may not generate cash flows from operations in the future that are sufficient to service our debt and support our growth strategies.
−Removed: In addition, our ability to generate sufficient cash flows to meet our debt obligations depends upon several factors, such as the ability of our Company and our licensees to timely complete clinical trials and obtain marketing approval for our clinical-stage product candidates, to successfully commercialize our clinical-stage product candidates, our receipt of regulatory approval for plozasiran for treatment of FCS, and our future performance, which is subject to financial, business, and other impacts on our operations, many of which are beyond our control.
+Added: In addition, our ability to generate sufficient cash flows to meet our debt obligations depends upon several factors, such as the ability of the Company and our licensees to timely complete clinical trials and obtain marketing approval for our clinical-stage product candidates, to successfully commercialize REDEMLPO and our clinical-stage product candidates, and our future performance, which is subject to financial, business, and other impacts on our operations, many of which are beyond our control.
If we are unable to generate sufficient cash flows, we may be required to adopt one or more alternatives, such as obtaining additional equity capital on terms that may be onerous or highly dilutive, selling assets, or restructuring debt.
Our ability to refinance our indebtedness will depend on the capital markets and our financial condition at such time.
−Removed: We may not be able to engage in
−Removed: any of these activities or engage in these activities on desirable terms, which could result in a default on our debt obligations.
+Added: We may not be able to engage in any of these activities or engage in these activities on desirable terms, which could result in a default on our debt obligations.
If the estimates we make, or the assumptions on which we rely, in preparing our consolidated financial statements prove inaccurate, our actual results may vary from those reflected in our accruals.
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As the variables that we use as a basis for valuing these awards change over time, including our underlying stock price and stock price volatility, the magnitude of the expense that we must recognize may vary significantly.
−Removed: Furthermore, our operating results may fluctuate due to a variety of other factors, may of which are outside of our control and may be difficult to predict, including the following:
+Added: Furthermore, our operating results may fluctuate due to a variety of other factors, many of which are outside of our control and may be difficult to predict, including the following:
+Added: • our ability to successfully commercialize REDEMPLO or any of our product candidates, if approved;
• the timing and cost of, and level of investment in, research and development activities relating to our current and any future product candidates, which will change from time to time;
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• the need to conduct unanticipated clinical trials or trials that are larger or more complex than anticipated;
−Removed: • competition from existing and potential future products that compete with any of our product candidates, and changes in the competitive landscape of our industry, including consolidation among our competitors or partners;
+Added: • competition from existing and potential future products that compete with REDEMPLO or any of our product candidates, and changes in the competitive landscape of our industry, including consolidation among our competitors or partners;
• any delays in regulatory review or approval of any of our product candidates;
−Removed: • the level of demand for any of our product candidates, if approved, which may fluctuate significantly and be difficult to predict;
−Removed: • the risk/benefit profile, cost and reimbursement policies with respect to our product candidates, if approved, and existing and potential future products that compete with our product candidates;
−Removed: • our ability to commercialize any of our product candidates, if approved, inside and outside of the United States, either independently or working with third parties;
+Added: • the level of demand for REDEMPLO or any of our product candidates, of approved, which may fluctuate significantly and be difficult to predict;
+Added: • the risk/benefit profile, cost and reimbursement policies with respect to REDEMPLO or any of our product candidates, if approved, and existing and potential future products that compete with our products;
+Added: • our ability to commercialize any of our products inside and outside of the United States, either independently or working with third parties;
• our ability to establish and maintain collaborations, licensing or other arrangements;
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This variability and unpredictability could also result in our failing to meet the expectations of industry or financial analysts or investors for any period.
−Removed: revenue or operating results fall below the expectations of analysts or investors or below any forecasts we may provide to the market, or if the forecasts we provide to the market are below the expectations of analysts or investors, the price of our common stock could decline substantially.
+Added: If our revenue or operating results fall below the expectations of analysts or investors or below any forecasts we may provide to the market, or if the forecasts we provide to the market are below the expectations of analysts or investors, the price of our common stock could decline substantially.
Such a stock price decline could occur even when we have met any previously publicly stated guidance we may provide.
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Under that provision, we can carryforward our NOLs to offset our future taxable income, if any, until such NOLs are used or expire.
−Removed: As o f September 30, 2024 , we had federal, state, and foreign NOL carryforwards of $223.1 million, $693.2 million, and $38.3 million, resp ectively.
As a result of the Coronavirus Aid, Relief, and Economic Security Act of 2020 (“CARES Act”) and legislation commonly referred to as the Tax Cuts and Jobs Act of 2017 (“2017 Tax Act”), NOLs arising before January 1, 2018, and NOLs arising after January 1, 2018, are subject to different rules.
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and over fifteen years for foreign-based expenditures.
−Removed: There is no assurance that the requirement will be deferred, repealed, or otherwise modified.
−Removed: This change in law increased our tax liability for the fiscal year.
+Added: The One Big Beautiful Bill Act, enacted in 2025, permits the expensing of certain research and development expenditures in the U.S.
+Added: incurred in tax years beginning in 2025, while amortization over fifteen years continues to be required for foreign-based expenditures.
We continue to monitor new tax legislation or other developments since significant changes in tax legislation, or in the interpretation of existing legislation, could materially and adversely affect our financial condition and operating results.
Additionally, we may be audited in various jurisdictions, and such jurisdictions may assess additional taxes, sales taxes and value-added taxes against us.
−Removed: Although we believe our tax estimates are reasonable, the final determination of
−Removed: any tax audits or litigation could be materially different from our historical tax provisions and accruals, which could have a material adverse effect on our operating results or cash flows in the period for which a determination is made.
−Removed: Our business is subject to changing regulations for corporate governance and public disclosure that has increased both our costs and the risk of noncompliance.
+Added: Although we believe our tax estimates are reasonable, the final determination of any tax audits or litigation could be materially different from our historical tax provisions and accruals, which could have a material adverse effect on our operating results or cash flows in the period for which a determination is made.
+Added: Our business is subject to changing regulations for corporate governance and public disclosure that have increased both our costs and the risk of noncompliance.
Each year we are required to evaluate our internal controls systems in order to allow management to report on and our Independent Registered Public Accounting Firm to attest to, our internal controls as required by Section 404 of the Sarbanes-Oxley Act.
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If one or more of the analysts downgrade our stock or comment negatively on our prospects, our stock price may decline.
−Removed: If one or more of these analysts cease to cover our industry or us or fail to publish reports about the Company regularly, our common stock could lose visibility in the financial markets, which could also cause our stock price or trading volume to decline.
+Added: If one or more of these analysts cease to cover our industry or us or fail to publish reports about the Company regularly, our common stock could lose
+Added: visibility in the financial markets, which could also cause our stock price or trading volume to decline.
Further, incorrect judgments, estimates or assumptions made by research analysts may adversely affect our stock price, particularly if subsequent performance falls below the levels that were projected by the research analyst(s), even if we did not set or endorse such expectations.
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Our common stock price has fluctuated significantly over the last several years and may continue to do so in the future, without regard to our results of operations and prospects.
−Removed: Bec ause we are still a clinical-stage pharmaceutical company and have not yet commercialized a drug, t here are few objective metrics by which our progress may be measured.
+Added: The stock market in general and the market for smaller pharmaceutical and biotechnology companies in particular have experienced extreme volatility that has often been unrelated to the operating performance of particular companies.
Consequently, we expect that the market price of our common stock will continue to fluctuate significantly.
−Removed: We may not continue to generate substantial revenue from the license or sale of our technology for several years, if at all.
+Added: We may not generate substantial revenue from the sale of our products for several years, if at all.
In the absence of product revenue as a measure of our operating performance, we anticipate that investors and market analysts will assess our performance by considering factors such as:
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• market perception and/or investor sentiment regarding our technology;
−Removed: • Announcements of actions taken by regulatory authorities, such as the U.S.
−Removed: Food and Drug Administration;
−Removed: • Announcements regarding developments in the RNA interference, antisense technologies, gene editing technologies or biotechnology fields in general;
+Added: • the success of competitive products or technologies;
+Added: • announcements of actions taken by regulatory authorities, such as the FDA;
+Added: • announcements regarding developments in the RNAi, antisense technologies, gene editing technologies or biotechnology fields in general;
• announcements regarding clinical trial results with our products or competitors’ products;
−Removed: • Market perception and/or announcements regarding other companies developing products in the field of biotechnology generally or specifically RNA interference;
+Added: • market perception and/or announcements regarding other companies developing products in the field of biotechnology generally or specifically RNAi;
• the issuance of competitive patents or disallowance or loss of our patent rights;
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These activities may subject us to numerous data privacy and security obligations governing the collection, use, disclosure, protection, and other processing of personal data, such as various laws, regulations, guidance, industry standards, external and internal data privacy and security policies, contractual requirements, and other obligations relating to data privacy and security.
−Removed: In the United States, there are both state and federal data privacy and security laws, including data breach notification laws, data privacy laws (including biometric privacy laws), consumer protection laws (e.g., Section 5 of the Federal Trade Commission Act), the Health Insurance Portability and Accountability Act (“HIPPA”), and other similar laws (e.g., wiretapping laws).
−Removed: For example, the California Consumer Privacy Act of 2018, as amended by the California Privacy Rights Act of 2020 (together, the “CCPA”) applies to personal data of consumers, business representatives, and employees, and requires businesses to provide specific disclosures in privacy notices and certain rights to California residents with respect to their personal data.
−Removed: The CCPA provides for civil penalties of up to $7,500 per intentional violation
−Removed: and $2,500 per unintentional violation and allows private litigants affected by certain data breaches to recover significant statutory damages.
+Added: In the United States, there are both state and federal data privacy and security laws, including data breach notification laws, data privacy laws (including biometric privacy laws and wiretapping laws), consumer protection laws (e.g., Section 5 of the Federal Trade Commission Act), and the Health Insurance Portability and Accountability Act (“HIPPA”), as amended by the Health Information Technology for Economic and Clinical Health Act of 2009 (“HITECH Act”), and the regulations promulgated thereunder.
+Added: For example, the California Consumer Privacy Act of 2018, as amended by the California Privacy Rights Act of 2020 (together, the “CCPA”), applies to personal data of consumers, including business representatives and employees, who are California residents, and requires businesses to provide specific disclosures in their privacy notices and affords certain rights to California residents with respect to their personal data.
+Added: However, the CCPA does not apply to protected health information that is subject to HIPAA/HITECH.
+Added: The CCPA provides for civil penalties of up to $7,500 per intentional violation and $2,500 per unintentional violation and allows private litigants affected by certain data breaches to recover significant statutory damages.
+Added: In addition, state health information privacy laws, such as California’s Confidentiality of Medical Information Act, Washington’s My Health My Data Act and the Nevada Consumer Health Data Privacy Law, govern the privacy and security of health-related information, specifically, may apply even when HIPAA/HITECH does not and impose additional requirements.
Outside the United States there are additional laws, regulations, and industry standards governing data privacy and security.
−Removed: For example, the General Data Protection Regulation (“GDPR”) and the GDPR as incorporated into UK law pursuant to the European Union (Withdrawal) Act 2018 (the “UK GDPR”) impose strict requirements for processing personal data, including health-related information.
−Removed: Under the GDPR and UK GDPR, companies may face fines of up to 20 million Euros or 4% of annual global revenue, whichever is greater;
−Removed: or private litigation related to processing of personal data.
−Removed: In addition, the GDPR and UK GDPR impose specific restrictions on the transfer of personal data to countries outside of the EEA and UK.
−Removed: Although there are currently various mechanisms that may be used to make such transfers in compliance with law, such as the EEA and UK’s standard contractual clauses, these mechanisms are subject to legal challenges.
−Removed: Additionally, companies that transfer personal data out of the EEA and UK to other jurisdictions are subject to scrutiny from regulators, individual litigants, and activities groups.
−Removed: Preparing for and complying with these obligations requires us to devote resources and may necessitate changes to our services, information technologies, systems, and practices and to those of any third parties that process personal data on our behalf.
+Added: For example, in the EEA, the General Data Protection Regulation (“GDPR”) and, in the UK, the GDPR as incorporated into UK law pursuant to the European Union (Withdrawal) Act 2018 (the “UK GDPR”) impose strict requirements for processing personal data, including health-related data which is subject to specific requirements.
+Added: Under the GDPR and UK GDPR, companies may face fines of up to 20 million Euros or 4% of annual global revenue, whichever is greater, , as well as claims from individuals who suffered damages as a result of an infringement.
+Added: In addition, the GDPR and UK GDPR impose specific restrictions on the transfer of personal data to countries outside of the EEA and UK that are not considered to provide an adequate level of data protection.
+Added: Although there are currently various mechanisms that may be used to ensure appropriate safeguards to the personal data, such as the EEA and UK’s standard contractual clauses, these mechanisms are subject to further requirements, in particular the conduct of transfer risk/impact assessments to verify if anything in the law and/or practices of the third country may impinge on the effectiveness of the safeguards in the context of the transfer at stake and, if so, to identify and adopt supplementary measures.
+Added: Additionally, companies that transfer personal data out of the EEA and UK to other jurisdictions are subject to potential scrutiny from regulators, individuals and associations.
+Added: In the EEA, beyond the GDPR framework, companies must also comply with national data protection laws, which supplement, interpret, and in some cases go beyond the GDPR or other EEA-level requirements, including with respect to health-related data.
+Added: Data protection authorities from the different member states may also implement certain variations, enforce data protection laws differently, and introduce additional national regulations and guidelines, which adds to the complexity of processing personal data in the EEA.
+Added: Guidance developed at both EEA level and at the national level in each member state concerning implementation and compliance practices is often updated or otherwise revised.
+Added: Violations of national laws can trigger administrative investigations, corrective orders, temporary or definitive bans on processing, and, in some jurisdictions, criminal penalties.
+Added: Additionally, our use of artificial intelligence may be subject to laws and evolving regulations regarding the use of artificial intelligence, including as they relate to controlling for data bias and antidiscrimination.
+Added: Preparing for and complying with these obligations require us to devote resources and may necessitate changes to our services, information technologies, systems, and practices and to those of any third parties that process personal data on our behalf.
If we or the third parties on which we rely fail, or are perceived to have failed, to address or comply with applicable data privacy and security obligations, we could face significant consequences, including but not limited to:
−Removed: government enforcement actions (e.g., investigations, fines, penalties, audits, inspections, and similar);
+Added: government regulatory enforcement actions (e.g., investigations, fines, penalties, audits, inspections, and similar);
litigation (including class-action claims);
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loss of customers;
−Removed: inability to process personal data or to operate in certain jurisdictions;
+Added: inability to process personal data or to operate in certain
+Added: jurisdictions;
limited ability to develop or commercialize our products;
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Economic and Industry Risks
−Removed: Unfavorable global economic conditions, whether brought about by material global crises, health epidemics, military conflicts or war, geopolitical and trade disputes or other factors, may adversely affect our business and financial results.
−Removed: Our business is sensitive to global economic conditions, which can be adversely affected by epidemics and other public health crises (such as the COVID-19 pandemic), political and military conflict, trade and other international disputes, significant natural disasters (including as a result of climate change) or other events that disrupt macroeconomic conditions.
−Removed: Adverse macroeconomic conditions, including inflation, slower growth or recession, new or increased tariffs and other barriers to trade, changes to fiscal and monetary policy or government budget dynamics (particularly in the pharmaceutical and biotech areas), tighter credit, higher interest rates, volatility in financial markets, high unemployment, labor availability constraints, currency fluctuations and other challenges in the global economy have in the past adversely affected, and may in the future adversely affect, us and our business partners and suppliers.
−Removed: For example, trade policies and geopolitical disputes (including as a result of China-Taiwan relations) and other international conflicts can result in tariffs, sanctions and other measures that restrict international trade, and can materially adversely affect our business, particularly if these measures occur in regions where we source our components or raw materials.
−Removed: For example, tensions between the United States and China have led to a series of tariffs being imposed by the United States on imports from China mainland, as well as other business restrictions.
+Added: Unfavorable global economic conditions, whether brought about by material global crises, health epidemics, military conflicts or war, geopolitical and tariffs or other trade disputes or other factors, may adversely affect our business and financial results.
+Added: Our business is sensitive to global economic conditions, which can be adversely affected by epidemics and other public health crises (such as the COVID-19 pandemic), political and military conflict, tariffs or other trade restrictions or the threat of such actions and retaliatory actions, and other international disputes, significant natural disasters (including as a result of climate change) or other events that disrupt macroeconomic conditions.
+Added: Adverse macroeconomic conditions, including inflation, slower growth or recession, new or increased tariffs and other trade restrictions or the threat of such actions and retaliatory actions, changes to fiscal and monetary policy or government budget dynamics (particularly in the pharmaceutical and biotech areas), tighter credit, higher interest rates, volatility in financial markets, high unemployment, labor availability constraints, currency fluctuations and other challenges in the global economy have in the past adversely affected, and may in the future adversely affect, us and our business partners and suppliers.
+Added: Trade policies and geopolitical disputes (including as a result of China-Taiwan relations) and other international conflicts can result in tariffs, sanctions and other measures that restrict international trade, and can materially and adversely affect our business, particularly if these measures occur in regions where we source components or raw materials.
+Added: For example, tensions between the United States and China have led to a series of tariffs being imposed by the United States on imports from mainland China, as well as other business restrictions.
+Added: In response to tariffs, countries have implemented retaliatory tariffs on U.S.
+Added: Furthermore, in September 2025, the current Presidential Administration announced plans to impose up to 100% tariffs on imported branded or patented pharmaceutical products, subject to certain exceptions.
+Added: There is substantial uncertainty as to when such tariffs may go into effect and whether such tariffs would apply to the importation of active pharmaceutical ingredients or bulk drug products that are intended for use in clinical trials, and, more generally,
+Added: about the duration of existing tariffs, implementation of announced tariffs, litigation challenging tariffs and whether additional tariffs or other retaliatory measures may be imposed, modified or suspended.
Tariffs increase the costs of the components and raw materials we source.
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These geopolitical risks could also adversely affect Visirna.
+Added: Political tensions as a result of trade policies could reduce trade volume, investment, technological exchange and other economic activities between major international economies, resulting in a material adverse effect on global economic conditions and the stability of global financial markets.
Further, military conflicts or wars (such as the ongoing conflicts between Russia and Ukraine and in the Middle East ) can cause exacerbated volatility and disruptions to various aspects of the global economy.
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For example, a number of our clinical trial sites we had previously planned to use in Russia, Ukraine, and Belarus were shut down and we had to seek alternatives in other geographies.
−Removed: We cannot be certain of the overall impact of the conflict between Russia and Ukraine on our ability to conduct and complete our clinical trials as planned, and any interruptions of our clinical trials can result in significant delays or termination of the research, development or commercialization of our drug candidates, which could impair our ability to generate revenues and harm our business and financial condition.
−Removed: Moreover, the conflict between
−Removed: Israel and Palestine could impact future business decisions to locate potential clinical trials in Israel .
+Added: Moreover, the conflict between Israel and Palestine could impact future business decisions to locate potential clinical trials in Israel .
It is not possible to predict the short and long-term implications of military conflicts or wars or geopolitical tensions which could include further sanctions, uncertainty about economic and political stability, increases in inflation rate and energy prices, cyber-attacks, supply chain challenges and adverse effects on currency exchange rates and financial markets.
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Any insurance we maintain against damage to our property and the disruption of our business due to disaster may not be sufficient to cover all of our potential losses and may not continue to be available to us on acceptable terms, or at all.
−Removed: Further, because the Company relies on single or limited sources for the supply and manufacture of many critical components, a business interruption affecting such sources would exacerbate any negative consequences to the Company.
+Added: Further, because the
+Added: Company relies on single or limited sources for the supply and manufacture of many critical components, a business interruption affecting such sources would exacerbate any negative consequences to the Company.
Any future public health crises may affect our operations and those of third parties on which we rely, including our business partners and suppliers.
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Throughout the world and particularly in the United States, the healthcare system is under significant financial pressure to reduce costs.
−Removed: The price of pharmaceuticals has been a topic of considerable public discussion that could lead to price controls or other price-limiting strategies by payors that have the effect of lowering payment and reimbursement rates for drugs or otherwise making the commercialization of pharmaceuticals less profitable.
+Added: The price of pharmaceuticals has been a topic of considerable public discussion that could lead to price controls or other price-limiting strategies by payers that have the effect of lowering payment and reimbursement rates for drugs or otherwise making the commercialization of pharmaceuticals less profitable.
Many federal and state legislatures have considered, and adopted, healthcare policies intended to curb rising healthcare costs, such as the Inflation Reduction Act of 2022.
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requirements to try less expensive products or generics before a more expensive branded product;
−Removed: and public funding for cost effectiveness research, which may be used by government and private third-party payors to make coverage and payment decisions.
+Added: and public funding for cost effectiveness research, which may be used by government and private third-party payers to make coverage and payment decisions.
+Added: In addition, in May 2025, the Trump administration issued an executive order entitled “Delivering Most-Favored-Nation Prescription Drug Pricing to American Patients,” which, among other things, directs the HHS and other agencies to communicate most-favored-nation (“MFN”) price targets to pharmaceutical manufacturers to
+Added: bring prices for U.S.
+Added: patients in line with comparably developed nations and to facilitate direct-to-consumer purchasing programs.
+Added: The HHS subsequently issued guidance indicating the MFN target price is the lowest price paid in an Organization for Economic Co-operation and Development country with a gross domestic product (“GDP”) per capita of at least 60% of the U.S.
+Added: GDP per capita.
+Added: It is currently unclear whether and to what extent these measures will be implemented and what impact any such implementation would have on our business.
+Added: Further, there can be no assurance that the current administration or future administrations will not pursue different or additional measures that could impact drug pricing in the U.S.
Political, economic and regulatory developments may further complicate developments in healthcare systems and pharmaceutical drug pricing.
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The implementation of any price controls, caps on prescription drugs or price transparency requirements could adversely affect our business, operating results and financial condition.
−Removed: Regulatory standards are subject to change over time, making it difficult to accurately predict the likelihood of marketing approval even when clinical trials meet their endpoints.
+Added: Evolving regulatory standards, including as a result of changes in government leadership, make it difficult to accurately predict the likelihood of marketing approval even when clinical trials meet their endpoints.
Regulatory standards are promulgated by various government entities and are subject to change based on factors such as scientific developments, public perceptions of risk, and political forces.
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As such, there can be no assurance that regulatory standards that are appropriate at the outset of a clinical trial program will not become more rigorous during the regulatory approval process and could potentially result in a delayed approval or denial of marketing authorization.
+Added: In addition, the FDA, EMA and other regulatory authorities may change their policies, issue additional regulations or revise existing regulations, or take other actions, including as a result of changes in leadership at the FDA and other federal agencies under the current U.S.
+Added: administration, which may prevent or delay approval of our future products under development on a timely basis.
+Added: Such policy or regulatory changes could impose additional requirements upon us that could delay our ability to obtain approvals, increase the costs of compliance or restrict our ability to maintain any marketing authorizations we may have obtained.
+Added: In June 2024, the Supreme Court overruled the Chevron doctrine, which had given deference to regulatory agencies’ statutory interpretations of ambiguous regulations in litigation against federal government agencies, such as the FDA.
+Added: The overruling of the Chevron doctrine may significantly increase the number of challenges brought by companies and other stakeholders against federal agencies such as the FDA and its longstanding decisions and policies, including the FDA’s statutory interpretations of market exclusivities and the “substantial evidence” requirements for drug approvals, which could undermine the FDA’s authority, lead to uncertainties in the industry, and disrupt the FDA’s normal operations, any of which could delay the FDA’s review of our regulatory submissions.
+Added: We cannot predict the full impact of this decision, future judicial challenges brought against the FDA, or the nature or extent of government regulation that may arise from future legislation or administrative action.
+Added: Further, under the new leadership at the HHS under the current administration, agency reorganization, mass layoffs due to the reduction in force initiative and other measures implemented by the Department of Government Efficiency may impact the normal operations of the FDA as well as other federal agencies.
+Added: FDA may lack adequate staff and resources to meet current review, approval, and inspection schedules, which could delay our anticipated timelines and may have a material impact on the industry and our clinical development plans.
+Added: For example, average review times at the FDA have fluctuated in recent years as a result.
+Added: Our business depends upon the ability of the FDA to accept and review our potential regulatory filings.
+Added: If a prolonged government shutdown occurs or if a significant number of federal employees are laid off or leave federal agencies, it could significantly impact the ability of the FDA to timely review and process our regulatory submissions, which could have a material adverse effect on our ability to advance clinical development of our product candidates.
+Added: In addition, government funding of other government agencies that fund research and development activities is subject to the political process, which is inherently fluid and unpredictable.
+Added: In January 2025, an executive order entitled “Unleashing Prosperity Through Deregulation”, was issued which calls for at least 10 existing regulations to be repealed whenever an executive department or agency publicly proposes for notice and comment or otherwise promulgates a new regulation.
+Added: Recent developments at the FDA include announcement of a plan to phase out animal testing for monoclonal antibodies
+Added: and certain other drugs, the proposed rare disease evidence principles (RDEP) program to facilitate approval of drugs to treat rare diseases with very small patient populations with significant unmet medical need and with a known genetic defect that is the major driver of the pathophysiology, and the announcement of a new Commissioner’s National Priority Voucher program for companies supporting certain U.S.
+Added: national health priorities and interests.
+Added: To the extent our competitors are selected for this new voucher pilot program, or are otherwise able to participate in any of these initiatives intended to accelerate drug development and application review, and obtain faster approval than us, our competitive position may be harmed.
+Added: FDA has also increased its scrutiny of foreign drug manufacturing facilities and other contractors based in China, especially with respect to the transfer of biological materials, genetic data, and other sensitive data of American patients to parties located in China.
+Added: It is unclear how our industry and our clinical programs will be impacted by policies and regulations implemented under the current administration and FDA leadership, or other executive orders.
+Added: There is significant uncertainty in the industry and how federal agencies like the FDA will change in the coming years under the current administration.
+Added: To the extent the agency reorganization and other agency changes lead to disruptions in FDA’s operations, our correspondence and regulatory review processes with the FDA may be materially delayed.
Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.