What changed in this filing

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Item 1A. Risk Factors

2026-03-19 compared with 2025-03-24 · 239 added, 183 removed, 1128 unchanged (27% of the section changed)

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Our ability to generate revenue from nomlabofusp or any future product candidates also depends on a number of additional factors, including our ability to:

• successfully complete development activities, including the remaining non-clinical studies and planned clinical trials for our product candidates;

• successfully complete development activities, including non-clinical studies and planned clinical trials for our product candidates;

• complete and submit BLAs to the FDA and MAAs to the EMA and obtain regulatory approval for indications for which there is a commercial market;

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Failure to obtain this necessary capital when needed would force us to delay, limit or terminate our product development efforts or other operations.

As of December 31, 2024, our existing cash, cash equivalents and marketable securities were $183.5 million, which we anticipate will fund our operations into the second quarter of 2026.

As of December 31, 2025, our existing cash, cash equivalents and marketable securities were $136.9 million.

Together with the $107.6 million in net proceeds from our recently completed February 2026 public offering, we expect this will fund operations into the second quarter of 2027.

We expect to continue to spend substantial and increasing amounts to conduct clinical trials of nomlabofusp and further research and development activities for nomlabofusp, and for any additional product candidates that we may develop, in-license or acquire in the future.

In addition, raising funds in the current economic environment may present substantial challenges, for example, any sustained disruption in the capital markets from adverse macroeconomic conditions, such as the disruption and uncertainty caused by inflationary pressures, rising interest rates, banking instability, monetary policy changes, changes in trade policies, including tariffs (including tariffs that have been or may in the future be imposed by the U.S.

In addition, raising funds in the current economic environment may present substantial challenges, for example, any sustained disruption in the capital markets from adverse macroeconomic conditions, such as the disruption and uncertainty caused by inflationary pressures, rising interest rates, banking instability, monetary policy changes, changes in trade policies, (including tariffs or other trade protection measures that have been or may in the future be imposed by the U.S.

or other countries), economic slowdowns or recessions, could negatively impact our ability to raise capital and we cannot predict the extent or duration of such macroeconomic disruptions.

Additionally our expenses will increase as we expand, through development, in-license or acquisition, our pipeline of product candidates.

If we obtain marketing approval for any of our product candidates, we will likely incur significant commercialization expenses related to product sales, marketing, manufacturing and distribution to the extent that such sales, marketing, manufacturing and distribution are not the responsibility of a future

collaborator.

If we obtain marketing approval for any

of our product candidates, we will likely incur significant commercialization expenses related to product sales, marketing, manufacturing and distribution to the extent that such sales, marketing, manufacturing and distribution are not the responsibility of a future collaborator.

Accordingly, we will need to obtain additional funding in connection with our continuing operations.

Our current cash, cash equivalents and marketable securities may not be sufficient to fund all of the efforts that we plan to undertake or to fund the completion of the development and commercialization of nomlabofusp.

Our current cash, cash equivalents and marketable securities augmented by the $107.6 million of net proceeds from our February 2026 public offering of our common stock may not be sufficient to completely fund all of the efforts that we plan to undertake or to fund the completion of the development and commercialization of nomlabofusp.

Accordingly, we may be required to obtain further funding through public or private equity offerings, debt financings, collaborations and licensing arrangements or other sources.

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We could also be required to seek funds through arrangements with collaborative partners or otherwise at an earlier stage than otherwise would be desirable and we may be required to relinquish rights to some of our technologies or product candidates or otherwise agree to terms unfavorable to us, any of which may have a material adverse effect on our business, operating results, financial condition and prospects.

In addition, geopolitical tension including, for example, the broader impact of the ongoing conflict between Russia and Ukraine and the current conflict in Israel and Gaza (including any escalation or expansion), and the impact of a future pandemic, epidemic or outbreak of an infectious disease or liquidity constraints, failures and instability in U.S.

In addition, geopolitical tension including, for example, the broader impact of the current conflict between the United States, the ongoing conflicts between Russia and Ukraine and the continuing conflict in the Middle East (including any further escalation or expansion), and the impact of a future pandemic, epidemic or outbreak of an infectious disease or liquidity constraints, failures and instability in U.S.

and international financial banking systems on the global financial markets may reduce our ability to access capital, which could negatively affect our liquidity.

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Our NOLs could expire unused and be unavailable to offset future income tax liabilities because of their limited duration or because of restrictions under U.S.

NOLs generated in taxable years beginning before January 1, 2018 are permitted to be carried forward for 20 taxable years under applicable U.S.

NOLs generated in taxable years beginning before January 1, 2018 are permitted to be carried forward for 20 taxable

years under applicable U.S.

federal income tax law.

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Moreover, NOLs generated in taxable years beginning after December 31, 2017 may be carried forward indefinitely.

As of December 31, 2024, the Company

had federal net operating loss carryforwards that were generated after December 31, 2017 of $159.5 million that do not expire, however these carryforwards are limited to 80% of the taxable income in any one tax period.

As of December 31, 2025, the Company had federal net operating loss carryforwards that were generated after December 31, 2017 of $343.9 million that do not expire;

however, these carryforwards are limited to 80% of the taxable income in any one tax period.

In general, under Section 382 of the Internal Revenue Code (the “Code”) if a corporation undergoes an “ownership change,” generally defined as a greater than 50% change (by value) in its equity ownership over a three-year period, the corporation’s ability to use its pre-change NOLs and other pre-change tax attributes (such as capitalized research and development costs and research tax credits) to offset its post-change income may be limited.

We believe that as a result of our merger with Zafgen, our ability to utilize NOLs acquired in the transaction and our other NOLs is expected to be severely limited by Section 382 of the Code.

Additionally, our July 2021, September 2022 and February 2024 equity transactions could also limit our ability to utilize NOLs in the future.

Additionally, our equity transactions executed between 2021 and 2026 through February 28, 2026 could also limit our ability to utilize NOLs in the future.

We may also experience ownership changes in the future as a result of subsequent shifts in our stock ownership.

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We cannot be certain that we will ultimately be successful with our clinical development or that we will ever be able to obtain regulatory approval for nomlabofusp.

We currently have no drug products for sale and our business is currently wholly dependent on our successful clinical development, regulatory approval and commercialization of nomlabofusp, our lead product candidate and our only product candidate in clinical development, for which we have completed two Phase 1 studies and a four-week, placebo-controlled Phase 2 dose exploration study.

We have an ongoing Phase 2 OLE trial in patients with FA and an ongoing PK run-in study in adolescent patients with FA.

In addition to the regulatory and manufacturing hurdles faced by our product candidate, the administration of a protein such as nomlabofusp may cause an immune response, resulting in the creation of antibodies directed against the protein.

These anti-drug antibodies can have no effect or can neutralize the effectiveness of the protein or require that higher doses be used to obtain a therapeutic effect.

Neutralizing antibodies may be detected at a later date or upon longer exposure periods and there can be no assurance that neutralizing antibodies will not be detected in the future.

Additionally, while nomlabofusp was selected by the FDA for participation in its Support for clinical Trials Advancing Rare disease Therapeutics (START) Pilot Program, it is unknown whether participation in the program will accelerate the development of nomlabofusp and whether the FDA will continue investing its resources in this program.

(i) two Phase 1 clinical studies in adults with FA, (ii) a Phase 2 dose exploration study in adults with FA and (iii) a PK run-in study in adolescents (12-17 years old) with FA.

We have an ongoing Phase 2 OL trial in adults and adolescents with FA.

In addition to the regulatory and manufacturing hurdles faced by our product candidate, the administration of a protein such as nomlabofusp may cause an immune response, resulting in the development of antibodies directed against the protein.

These anti-drug antibodies can have no effect, may cause allergic reactions or may neutralize the effectiveness of the protein, or may require that different doses be used to obtain a therapeutic effect.

Additionally, while nomlabofusp was selected by the FDA for participation in its Support for clinical Trials Advancing Rare disease Therapeutics (START) Pilot Program and while nomlabofusp was awarded Breakthrough Therapy designation, it is unknown whether participation in either or both of these programs will accelerate the development of nomlabofusp and whether the FDA will continue investing its resources in the START program.

If our efforts to develop and commercialize nomlabofusp for the treatment of FA are unsuccessful, or we experience significant delays in doing so, our business could also be substantially harmed.

The success of nomlabofusp will depend on several factors, including the following:

• maintaining our IND with the FDA in order to continue to conduct clinical trials in the United States;

• successfully submitting a BLA for accelerated approval;

• maintaining our IND with the FDA in order to continue to conduct clinical trials in the United States and similarly maintaining clinical trial applications to conduct clinical trials in other countries;

• successfully submitting a BLA as well as foreign marketing authorization applications;

• successfully recruiting, enrolling and retaining patients in and completing any clinical trials, if allowed to continue, including trials in pediatric patients;

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Furthermore, we cannot provide assurance that we will be able to successfully progress any future non-clinical programs from candidate identification to Phase 1 clinical development.

As is typical in candidate development, we have a program of toxicology studies in animals for nomlabofusp and cannot provide assurance that the findings from such studies or any ongoing or future clinical trials will not adversely affect the clinical development of nomlabofusp.

As is typical in candidate development, we cannot provide assurance that the findings from such non-clinical studies or any ongoing or future clinical trials will not adversely affect the clinical development of product candidate.

For the foregoing reasons, we cannot be certain that our non-clinical studies and clinical trials will be successful.

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Failures or delays in the completion of our clinical trials could result in increased costs and could delay, prevent or limit our ability to generate revenue and continue our business.

For our lead product candidate nomlabofusp, we have completed two Phase 1 clinical trials in patients with FA and our four-week, placebo-controlled Phase 2 dose exploration study.

We have an ongoing Phase 2 OLE trial in patients with FA and an ongoing run-in study in adolescent patients with FA.

For our lead product candidate nomlabofusp, we have completed four clinical studies in patients with FA:

(i) two Phase 1 clinical studies in adults, (ii) a Phase 2 dose exploration study in adults and (iii) a PK run-in study in adolescents (12-17 years old).

Our clinical trials may be delayed or terminated as a result of safety issues in non-clinical or clinical trials, ambiguous or negative interim results or events outside of our control.

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In addition, disruptions caused by future pandemic, epidemic or outbreak of an infectious disease, may increase the likelihood that we encounter such difficulties or delays in initiating, enrolling, conducting or completing our planned and ongoing clinical trials.

Further, FA is a rare disease and as a result, there are a limited number of patients in close proximity to clinical trial sites and clinical trial patients may need to travel from other countries to the clinical trial sites in order to participate.

Further, FA is a rare disease and as a result, there are a limited number of patients in close proximity to clinical trial sites and clinical trial participants may need to travel from other countries to the clinical trial sites in order to participate.

In addition, given the limited number of FA patients, the approval of a competing therapy for the treatment of FA may make patients less likely to enroll in our clinical trials or less likely to be eligible for our clinical trials.

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In addition, our research methodology may be unsuccessful in identifying potential product candidates or our potential product candidates may be shown to have harmful side effects or may have other characteristics that may make the products unmarketable or unlikely to receive marketing approval.

Research programs to identify new product candidates require substantial technical, financial and human resources.

Research programs to identify new product candidates require substantial technical, financial and human resources, which we may not have access to.

We may focus our efforts and resources on potential programs or product candidates that ultimately prove to be unsuccessful.

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We have no marketed proprietary products and have not yet advanced a product candidate beyond Phase 2 clinical trials, which makes it difficult to assess our ability to develop nomlabofusp or any future product candidates and commercialize any resulting products independently.

We have little experience in later stage clinical development, and related regulatory requirements or the commercialization of products.

We have little experience in later stage clinical development, and conducting global trials as well as related regulatory requirements or the commercialization of products.

As a result, we have not yet demonstrated our ability to independently and repeatedly conduct clinical development after Phase 2, successfully conduct an international multi-center clinical trial, conduct a pivotal clinical trial, obtain regulatory approval, manufacture drug product on a commercial scale or arrange for a third party to do so on our behalf, and commercialize therapeutic products.

We will need to develop such abilities if we are to execute on our business strategy to develop and independently commercialize product

candidates for orphan and niche indications.

We will need to develop such abilities if we are to execute on our business strategy to develop and independently commercialize product candidates for orphan and niche indications.

To execute on our business plan for the development of independent programs, we will need to successfully:

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We submitted our IND and it was accepted, permitting the conduct of clinical trials.

We completed two Phase 1 and our four-week, placebo-controlled Phase 2 dose exploration study.

We have completed four clinical studies in patients with FA:

(i) two Phase 1 clinical studies in adults, (ii) a Phase 2 dose exploration study in adults and (iii) a Phase 1 PK run-in study in adolescents (12-17 years old).

We have an ongoing Phase 2 OL trial in adults and adolescents.

In clinical development of any product candidate, the outcome of toxicology studies and early clinical trials may not be positive and may not be predictive of the success of later non-clinical studies or clinical trials.

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These uncertainties are enhanced where the diseases under study lack established clinical endpoints, validated measures of efficacy, as is often the case with orphan diseases for which no drugs have been developed previously and where the product candidates target novel mechanisms.

For example, to our knowledge, nomlabofusp is the only protein replacement therapy being developed for the treatment of FA and therefore non-clinical studies may not be adequate to predict efficacy in a clinical trial due to our novel protein replacement therapy platform.

For example, nomlabofusp is a novel protein replacement therapy platform and therefore non-clinical studies may not be adequate to predict efficacy in a clinical trial.

In some instances, there can be significant variability in safety or efficacy results between different clinical trials of the same product candidate due to numerous factors, including changes in trial procedures set forth in protocols, differences in the size and type of the patient populations, such as pediatric patients, variability of the disease being studied, changes in and adherence to the dosing regimen and other clinical trial protocols and the rate of dropout among clinical trial participants.

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Further, nomlabofusp or any future product candidates may not be approved even if they achieve their primary endpoint in clinical trials.

The FDA, EMA or foreign regulatory authorities may disagree with our trial design and our interpretation of data from non-clinical studies and clinical trials.

In addition, FDA, EMA or foreign regulatory authorities may disagree with the extent of population exposure to assess clinical safety.

Any of these regulatory authorities may change its requirements for the approval of a product candidate even after reviewing and providing comments or advice on a protocol for a pivotal clinical trial that, if successful, would potentially form the basis for

an application for approval by the FDA, EMA or another regulatory authority.

The FDA, EMA or other foreign regulatory authorities may disagree with our trial design and our interpretation of data from non-clinical studies and clinical trials.

In addition, FDA, EMA or other foreign regulatory authorities may disagree with the extent of population exposure to assess clinical safety.

Furthermore, any of these regulatory authorities may also approve nomlabofusp or any future product candidates for a narrower indication than we may request or may grant approval contingent on the performance of costly post-marketing clinical trials.

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Supreme Court’s July 2024 decision to overturn prior established case law giving deference to regulatory agencies’ interpretations of ambiguous statutory language has introduced uncertainty regarding the extent to which FDA’s regulations, policies and decisions may become subject to increasing legal challenges, delays, and/or changes.

We may experience difficulties identifying and enrolling patients in our clinical trials given the limited number of patients who have the disease for which nomlabofusp is being studied or for any other product candidate we may study in the future.

We may experience difficulties identifying and enrolling patients in our clinical trials given the number of ongoing trials being conducted and the limited number of patients who have the disease for which nomlabofusp is being studied or for any other product candidate we may study in the future.

Difficulty in enrolling patients could delay or prevent clinical trials of nomlabofusp or any future product candidate.

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The conditions for which we are planning to evaluate nomlabofusp and any product candidates we may evaluate in the future, are rare genetic diseases.

Accordingly, there are limited patient pools from which to draw for clinical trials.

Arranging for investigative sites and recruiting patients for clinical trials in this disease may be very difficult.

The recent FDA approval of a product for the treatment of FA may impact our ability to enroll patients in our clinical trials as patients using other FA treatments may be excluded from participation in our nomlabofusp studies or may be less likely to participate in our nomlabofusp clinical trials due to the availability of another FA therapy.

If other companies are studying their investigational products in Friedreich’s ataxia and/or if other companies have their products approved for the treatment of FA, it may be more difficult to enroll eligible patients into our clinical trials.

Accordingly, there are limited patient pools from which to draw for clinical trials and multiple developers competing for access to conduct their research in those same limited patient pools with the same experienced investigators or research sites.

Accordingly, arranging for investigative sites and recruiting patients for clinical trials in this disease may be very difficult.

Current and future approvals of products for the treatment of FA may impact our ability to enroll patients in our clinical trials as patients using other FA treatments may be excluded from participation in our nomlabofusp studies or may be less likely to participate in our nomlabofusp clinical trials due to the availability of another FA therapy.

If other companies are studying their investigational products in FA and/or if other companies have their products approved for the treatment of FA, it may be more difficult to identify available study sites and investigators to enroll eligible patients into our clinical trials.

Competing priorities at sites and participation of subjects in other studies may limit our ability to execute clinical trials in a timely fashion, if at all.

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The availability and efficacy of approved and competing therapies and clinical trials can also adversely impact enrollment.

Furthermore, our inability to enroll a sufficient number of patients for our clinical trials, including pediatric clinical trials, could result in significant delays or may require us to abandon one or more clinical trials altogether.

Furthermore, our inability to enroll

a sufficient number of patients for our clinical trials, including pediatric clinical trials, could result in significant delays or may require us to abandon one or more clinical trials altogether.

Enrollment delays in our clinical trials may result in increased development costs for nomlabofusp or any future product candidates, and jeopardize our ability to achieve our clinical development timeline and goals, including the dates by which we will commence, complete and receive results from clinical trials.

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There are currently no FDA-approved products to treat FA that are designed to increase frataxin levels.

We have concentrated our research and development efforts on developing a novel, FA therapy designed to address frataxin deficiency, which is the underlying cause of the disease, and our future success depends on the success of

this therapeutic approach.

The clinical trial requirements of the FDA and other comparable regulatory agencies and the criteria these regulators use to determine the safety and efficacy of any product candidate vary substantially according to the type, complexity, novelty and intended use and market of the potential product.

We have had discussions with the FDA regarding the use of tissue FXN levels as a novel surrogate endpoint.

The FDA acknowledged that frataxin deficiency appears to be critical to the pathogenic mechanism of FA, and that there continues to be an unmet need for treatments for FA patients that address the underlying disease pathophysiology.

In March 2025, we announced that FDA stated in written correspondence associated with a meeting through the START pilot program that they are open to considering the use of FXN concentration as a reasonably likely surrogate endpoint ("RLSE") and the acceptability of FXN’s use as an RLSE would ultimately be a matter of review of the data in a future marketing application.

We intend to pursue an accelerated approval using FXN levels, supportive PD and clinical information, and safety data from the OLE study, along with non-clinical pharmacology information needed to support the novel surrogate endpoint approach.

We are beginning to plan for a confirmatory study and are targeting a BLA submission by the end of 2025.

The FDA or other regulatory authorities may not agree with this approach.

Regulatory authorities in the United States, the United Kingdom and the European Union have not issued definitive guidance as to how to measure and achieve efficacy in treatments for FA.

As a result, the design and conduct of clinical trials of nomlabofusp may take longer, be more costly or be less effective as part of the novelty of development in FA.

The FDA may not accept that the supportive PD and clinical information, and safety data from the OLE study, along with additional non-clinical pharmacology data we ultimately submit in our BLA, adequately supports the use of FXN levels as a novel surrogate endpoint.

The FDA may not accept that the supportive PD and clinical information, and safety data from the OL study, along with additional non-clinical pharmacology data we ultimately submit in our BLA, adequately supports the use of FXN levels as a novel surrogate endpoint.

Even if the FDA supports the use of FXN levels as a novel surrogate endpoint, the FDA may not agree with the adequacy of the design of clinical trials intended to assess this novel surrogate endpoint.

Even if applicable regulatory authorities do not object to our proposed endpoints in an earlier stage clinical trial, such regulatory authorities may require evaluation of additional or different clinical endpoints in later-stage clinical trials.

Furthermore, if FDA grants accelerated approval of nomlabofusp based on FXN as a novel surrogate endpoint, we will be required to conduct a confirmatory study to verify and describe the clinical benefit of nomlabofusp, which may not be completed or which may fail to verify and describe the clinical benefit of nomlabofusp.

If the confirmatory study is not successful or if the FDA determines that it does not verify or describe the clinical benefit of nomlabofusp, the FDA may not grant traditional approval and/or the accelerated approval may be withdrawn.

Nomlabofusp, including the effects of long-term daily patient dosing, may cause adverse events or undesirable side effects in clinical trials that could delay or prevent its regulatory approval, limit the commercial profile of approved labeling, or result in significant negative consequences following regulatory approval, if any.

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It is possible that as we progress nomlabofusp through clinical trials and toxicology studies, or as the use of nomlabofusp becomes more widespread if it receives regulatory approval, illnesses, injuries, discomforts and other adverse events that were not observed in earlier trials, as well as conditions that did not occur or went undetected in previous trials, may be reported by patients.

For example, recently our Safety Monitoring Team deemed anaphylaxis as an adverse drug reaction likely associated with nomlabofusp.

To reduce the risk of allergic reactions, including anaphylaxis, we amended the OLE protocol to administer premedication for the first month of dosing.

If such side effects become known or their incidence increases later in development or after approval, such findings may harm our business, financial condition and prospects significantly.

Further, if a serious safety issue is identified in connection with the use of nomlabofusp commercially or in third-party clinical trials elsewhere, such issues may adversely affect the development potential of nomlabofusp elsewhere or result in regulatory authorities restricting our ability to develop or commercialize nomlabofusp, if approved.

For example, anaphylaxis is an adverse drug reaction associated with nomlabofusp.

To reduce the risk of allergic reactions, including anaphylaxis, we have implemented risk mitigation measures in the OL study protocol and the Phase 3 confirmatory study protocol, including modifying the starting dose regimen and supplying epinephrine autoinjectors.

Such side effects could cause regulatory authorities to impose additional requirements for drug approval labeling and marketing.

If such side effects become known or their incidence increases later in development or after approval, other such findings may harm our business, financial condition and prospects significantly.

nomlabofusp elsewhere or result in regulatory authorities restricting our ability to develop or commercialize nomlabofusp, if approved.

Further, if nomlabofusp were to receive marketing approval and we or others identify undesirable side effects caused by the product (or any other product) after the approval, a number of potentially significant negative consequences could result, including:

• regulatory authorities may request that we recall or withdraw the product from the market or may limit the approval of the product through labeling or other means;

• regulatory authorities may require the addition of labeling statements, such as a “boxed” warning or a contraindication or a precaution, or labeling restrictions based on patient population;

• regulatory authorities may require the addition of labeling statements, such as a “boxed” warning or a contraindication or a precaution, or additional labeling restrictions or REMS requirements based on patient population;

• we may be required to change the way the product is distributed or administered, conduct additional clinical trials or change the labeling of the product;

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In addition, the patient populations under investigation with nomlabofusp have many co-morbidities that may cause severe illness or death unrelated to our product candidate, which may be attributed to nomlabofusp in a manner that negatively affects the safety profile of our product candidate.

Interim, “top-line,” and preliminary data from our clinical trials that we announce or publish from time to time may change as more patient data become available or as additional analyses are conducted, and as the data are subject to audit and verification procedures that could result in material changes in the final data.

From time to time, we may publish interim, preliminary or “top-line” data from our clinical trials.

Interim, “top-line,” and preliminary results from our clinical trials that we announce or publish from time to time may change as more patient data become available or as additional analyses are conducted, and as the data are subject to audit and verification procedures that could result in material changes in the final data.

From time to time, we may publish interim, preliminary or “top-line” results from our clinical trials.

Interim data from clinical trials that we may complete are subject to the risk that one or more of the clinical outcomes may materially change as patient enrollment continues and more patient data become available.

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The manufacture of fusion proteins, such as nomlabofusp and any fusion protein candidates, is technically complex and necessitates substantial expertise and capital investment.

Production difficulties caused by unforeseen events may delay the availability of material for clinical trials and commercial products for nomlabofusp or any

fusion protein product that may receive regulatory approval in the future.

Production difficulties caused by unforeseen events may delay the availability of material for clinical trials and commercial products for nomlabofusp or any fusion protein product that may receive regulatory approval in the future.

Additionally, because biologic products are complex, the manufacture of such products and product candidates is more difficult and costly.

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Our current dependence upon others for the manufacture of our product candidates may also adversely affect our business, results of operations, financial condition, and our ability to commercialize any product candidates that receive regulatory approval on a timely and competitive basis.

Fast track designation by the FDA or any future expedited program designations may not lead to a faster development, regulatory review or approval process and it does not increase the likelihood that any of our product candidates will receive marketing approval.

We have received fast track therapy designation for nomlabofusp for the treatment of FA.

We may, in the future, apply for other expedited program designations from the FDA (such as breakthrough therapy) for nomlabofusp or future product candidates.

The FDA's Fast track Designation and its Breakthrough Therapy Designation or any future expedited program designations may not lead to a faster development, regulatory review or approval process and it does not increase the likelihood that any of our product candidates will receive marketing approval.

We have received Fast Track Designation and Breakthrough Therapy Designation for nomlabofusp for the treatment of FA.

We may, in the future, apply for other expedited program designations from the FDA for nomlabofusp or future product candidates.

Designation for these programs is within the discretion of the FDA.

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The receipt of a designation may not result in a faster development process, review or approval compared to products considered for approval without these expedited program designations and, in any event, does not assure ultimate approval by the FDA.

In addition, even though nomlabofusp has obtained fast track designation, the FDA may later decide that it no longer meets the criteria for designation and revoke it.

Approval of other therapies for the treatment Friedreich’s ataxia could negatively impact our continued fast track therapy designation for nomlabofusp for the treatment of FA.

In addition, if we apply to the FDA for other designations for nomlabofusp or future product candidates, the FDA might not grant such designations.

If we apply for any similar programs in foreign countries for nomlabofusp or future product candidates, those designations also might not be granted by the regulatory authorities of those countries.

In addition, even though nomlabofusp has obtained Fast Track Designation and Breakthrough Therapy Designation, the FDA may later decide that it no longer meets the criteria for designation and revoke it.

Approval of other therapies for the treatment of FA could negatively impact our continued Fast Track Designation or Breakthrough Therapy Designation for nomlabofusp for the treatment of FA.

In addition, if we apply to the FDA for other designations for nomlabofusp or future product candidates, the FDA

might not grant such designations.

If we have or apply for any similar programs in foreign countries for nomlabofusp or future product candidates, those designations also might not be granted by the regulatory authorities of those countries, and also could be revoked if circumstances change.

Any of the above could adversely affect our business, financial condition and results of operations.

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If we are unable to obtain approval under an accelerated pathway, we may be required to conduct additional clinical trials beyond those that we contemplate, which could increase the expense of obtaining, reduce the likelihood of obtaining, and/or delay the timing of obtaining, necessary marketing approvals.

We intend to pursue an accelerated approval from FDA for nomlabofusp for the treatment of FA using FXN concentrations as a surrogate endpoint, supportive pharmacodynamic and clinical information and safety data from the OLE study, along with non-clinical pharmacology information needed to support our surrogate biomarker

We intend to pursue an accelerated approval from FDA for nomlabofusp for the treatment of FA using FXN concentrations as a surrogate endpoint, supportive pharmacodynamic and clinical information and safety data from the OL study, along with non-clinical pharmacology information needed to support our surrogate biomarker approach.

Under the FDA’s accelerated approval program, the FDA may approve a drug or biologic for a serious or life-threatening illness that provides meaningful therapeutic benefit to patients over existing treatments based upon a surrogate endpoint that is reasonably likely to predict clinical benefit, or on a clinical endpoint that can be measured earlier than irreversible morbidity or mortality, that is reasonably likely to predict an effect on irreversible morbidity or mortality or other clinical benefit, taking into account the severity, rarity, or prevalence of the condition and the availability or lack of alternative treatments.

The FDA stated in written correspondence associated with a meeting through the START pilot program that they are open to considering the use of FXN concentration as an RLSE and the acceptability of FXN’s use as an RLSE would ultimately be a matter of review of the data.

There can be no assurance that data we intend to generate will be successful in establishing that increases in FXN concentrations are reasonably likely to predict clinical benefit or that increases in FXN concentrations due to treatment with nomlabofusp meet the legal standards to support approval of a marketing application.

In addition, non-clinical pharmacology and clinical studies may not provide adequate information or may fail to support the predictive value of increases in FXN and, therefore, its ability to serve as a surrogate endpoint, or may fail to support that increases in FXN are the result of treatment with nomlabofusp.

Even if these evidentiary requirements are met, we may not be able to accrue adequate exposures to assess clinical safety or expedite the scale up of manufacturing or meet other CMC requirements in a timeframe commensurate with the expedited assessment of clinical efficacy.

Approval of other therapies for the treatment of FA, including the approval of omaveloxolone for the treatment of FA, could negatively impact our ability to utilize the accelerated approval pathway, and/or get approval for nomlabofusp.

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FDORA enables the FDA to initiate enforcement action for a sponsor's failure to conduct with due diligence a required post-approval study, including a failure to meet any required conditions specified by the FDA or to submit timely reports.

We are targeting to submit a BLA to the FDA in June 2026 for marketing approval of nomlabofusp using the accelerated approval pathway;

however, there can be no assurance FDA will approve our BLA submission for accelerated approval.

Moreover, if FDA grants accelerated approval of nomlabofusp, there is no assurance that the FDA will grant traditional approval or that the accelerated approval will not be withdrawn.

We are targeting to submit a BLA to the FDA in June 2026 to request marketing approval of nomlabofusp.

We may not be able to obtain, and there can be no assurance that the FDA will agree that the data submitted in any BLA is adequate to support approval, including accelerated approval.

Further, the FDA stated that the adequacy of the safety database will be a matter of review at the time of BLA submission.

In particular, the FDA may refuse to accept our planned BLA for substantive review (thereby issuing a “refuse to file” letter) or may conclude after review of our data that our application is insufficient to obtain regulatory approval (thereby issuing a “complete response” letter).

If the FDA does not accept or approve our planned BLA, the agency may require that we conduct additional clinical, non-clinical or manufacturing studies before it will reconsider our application.

Depending on the extent of these or any other studies required by the FDA, approval of a BLA may be significantly delayed or we may be unable to obtain approval of a BLA because such studies may require us to expend more resources than we have available.

It is also possible that additional studies, if performed and completed, may not be considered sufficient by the FDA.

For example, if the FDA does accept our BLA for filing, the FDA could determine after review of our BLA that the increases in FXN shown in our clinical trials are not reasonably likely to predict clinical benefit, that the nomlabofusp safety database was not of sufficient size to demonstrate the safety of nomlabofusp or that we otherwise failed to provide information sufficient to approve the nomlabofusp BLA.

Moreover, if FDA grants accelerated approval of nomlabofusp, we will be required to conduct a confirmatory study to verify and describe the clinical benefit of nomlabofusp, which may not be completed or which may fail to verify and describe the clinical benefit of nomlabofusp.

If any of these outcomes occurs, we may be forced to abandon our

planned BLA, which will materially adversely affect our business and could potentially cause us to cease

Furthermore, the FDA may approve nomlabofusp for a narrower indication or population than we request or may grant approval contingent on the performance of costly post-marketing commitments beyond our planned confirmatory study.

We face similar regulatory risks in foreign jurisdictions.

If we fail to maintain orphan drug designation or other regulatory exclusivity for nomlabofusp or obtain such exclusivity for any of our other product candidates in the future, our competitive position would be harmed.

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In the United States, orphan drug designation entitles a party to financial incentives such as tax advantages and user-fee waivers.

means that the FDA may not approve any other applications, including an NDA or BLA, to market the same drug for the same disease or condition for seven years, except in limited circumstances, including if the FDA concludes that the later drug is clinically superior to the approved drug.

In addition, if a product candidate that has orphan drug designation subsequently receives the first FDA approval for the disease for which it has such designation, the product is entitled to orphan drug exclusivity, which means that the FDA may not approve any other applications, including an NDA or BLA, to market the same drug for the same disease or condition for seven years, except in limited circumstances, including if the FDA concludes that the later drug is clinically superior to the approved drug.

A drug is clinically superior if it is safer, more effective, or makes a major contribution to patient care.

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We have also received orphan designation for nomlabofusp in the European Union.

In the European Union, the European Commission may grant orphan designation in respect of products that are intended for the diagnosis, prevention or treatment of a life threatening or chronically debilitating condition affecting not more than five in 10,000 persons in the European Union.

Additionally, designation is granted for products intended for the diagnosis, prevention or treatment of a life threatening, seriously debilitating or serious and chronic condition and when, without incentives, it is unlikely that sales of the drug in the European Union would be sufficient to justify the necessary investment in developing the drug.

In each case, orphan designation is only available if there is no other satisfactory method approved in the European Union of diagnosing, preventing, or treating the condition, or if such a method exists, the proposed orphan product will be of significant benefit to patients over the existing options.

In the European Union, orphan drug designation also entitles a party to financial incentives such as reduction of fees or fee waivers and ten years of market exclusivity following the grant of marketing authorization.

This period may be reduced to six years if the orphan drug designation criteria are no longer met, including where it is shown that the product is sufficiently profitable so that market exclusivity is no longer justified.

Loss of orphan drug designation for nomlabofusp or the failure to obtain such designation in other countries or for any future product candidates could adversely affect our business, financial condition and results of operation.

In the European Union, the European Commission may grant orphan designation, following an opinion from the EMA's Committee for Orphan Medicinal Products (COMP), for products intended for the diagnosis, prevention or treatment of a life-threatening or chronically debilitating condition affecting not more than five in 10,000 persons in the European

Alternatively, designation may be granted for products intended for the diagnosis, prevention or treatment of a life-threatening, seriously debilitating or serious and chronic condition and where, without incentives, it is unlikely that sales of the drug in the European Union would be sufficient to justify the necessary investment in developing the drug.

In each case, orphan designation is only available if there is no other satisfactory method authorized for marketing in the European Union for diagnosing, preventing or treating the condition, or if such a method exists, the proposed orphan product will be of significant benefit to patients over existing options.

In the European Union, orphan designation also entitles a party to financial incentives such as reduction of fees and ten years of market exclusivity following the grant of marketing authorization.

This period may be reduced to six years if it is determined at the end of the fifth year that the orphan designation criteria are no longer met, including where it is shown that the product is sufficiently profitable such that maintenance of market exclusivity is no longer justified.

If another product has received approval in the indications for which we have received orphan drug designation, we may still receive approval in that indication if we can demonstrate that our product candidate is clinically superior to the existing orphan product.

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The sponsor of an application for a rare pediatric disease drug product may be eligible for a voucher that can be used or sold to obtain a priority review for a subsequent application submitted under section 505(b)(1) of the FDCA or section 351 of the PHS Act.

The rare pediatric disease priority review voucher program began to sunset on December 20, 2024, due to failure to pass a continuing resolution package that included its reauthorization.

Under the amended statutory sunset provisions, after December 20, 2024, the FDA may award a priority review voucher for an approved rare pediatric disease product application only if the sponsor has rare pediatric disease designation for the drug and if that designation was granted by December 20, 2024.

After September 30, 2026, the FDA may not award any rare pediatric disease priority review vouchers.

Congress may vote to reauthorize this program, but its future remains unknown at this time.

The rare pediatric disease priority review voucher program was reauthorized by Congress.

Under current law, after September 30, 2029, the FDA may not award any rare pediatric disease priority review vouchers although the FDA's authority to do so could be extended by Congress in the future.

We received rare pediatric disease designation from the FDA for nomlabofusp in 2019.

We may, in the future, apply for rare pediatric disease designation from the FDA for future product candidates that may qualify for designation if Congress reauthorizes the program.

Vouchers for rare pediatric disease drugs are awarded for qualifying applications when the drug receives approval.

We may, in the future, apply for rare pediatric disease designation from the FDA for future product candidates that may qualify for designation.

Vouchers for rare pediatric disease drugs are awarded for qualifying applications if properly requested when the drug receives approval.

Although nomlabofusp has received rare pediatric disease designation, nomlabofusp may not receive a priority review voucher for a number of reasons:

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nomlabofusp may receive approval in adults, but not pediatric patients;

nomlabofusp may not meet the eligibility requirements for a priority voucher at

the time we seek approval for nomlabofusp;

or we may not meet the current deadline for receiving a priority review voucher (September 30, 2026), in which case we would not be able to obtain a voucher unless Congress further reauthorizes the program.

nomlabofusp may not meet the eligibility requirements for a priority voucher at the time we seek approval for nomlabofusp;

or we may not meet the current deadline for receiving a priority review voucher (September 30, 2029), in which case we would not be able to obtain a voucher unless Congress further reauthorizes the program in the future.

Finally, a rare pediatric disease designation does not necessarily lead to faster development or regulatory review of the product or increase the likelihood that it will receive marketing approval.

If the program is reauthorized and we apply for designation for future product candidates as drugs for rare pediatric diseases, the FDA may not grant the designation.

If the program is reauthorized and we apply for designation for future product candidates as drugs for rare pediatric diseases, the FDA may not find that those candidates meet the criteria for designation and may not grant the designation.

The failure to maintain rare pediatric disease designation for nomlabofusp or if FDA approval does not occur prior to September 30, 2029 could result in the inability to receive a priority review voucher which could adversely affect our business, financial condition and results of operations.

If we fail to maintain PRIME designation in the European Union for nomlabofusp, our competitive position could be harmed.

The PRIME scheme is open to medicines under development and for which the applicant intends to apply for an MA through the centralized procedure.

Eligible products must target conditions for which where is an unmet medical need (there is no satisfactory method of diagnosis, prevention or treatment in the European Union or, if there is, the new medicine will bring a major therapeutic advantage in comparison to existing therapies) and they must demonstrate the potential to address the unmet medical need by introducing new methods or therapy or improving existing ones.

The PRIME scheme is open to medicines under development for which the applicant intends to apply for an MA through the centralized procedure.

Eligible products must target conditions for which there is an unmet medical need (there is no satisfactory method of diagnosis, prevention or treatment in the European Union or, if there is, the new medicine will bring a major therapeutic advantage in comparison to existing therapies) and they must demonstrate the potential to address the unmet medical need by introducing new methods of therapy or improving existing ones.

Applicants will typically be at the exploratory clinical trial phase of development and will have preliminary clinical evidence in patients to demonstrate the promising activity of the medicine and its potential to address, to a significant extent, an unmet medical need.

In exceptional cases, applicants from the academic sector or SMEs may submit an eligibility request at an earlier stage of development if compelling non-clinical data in a relevant model provide early evidence of promising activity to establish proof of principle, and first in man studies indicate adequate exposure for the desired pharmacotherapeutic effects and tolerability.

In exceptional cases, applicants from the academic sector or SMEs may submit an eligibility request at an earlier stage of development if compelling non-clinical data in a

relevant model provide early evidence of promising activity to establish proof of principle, and first-in-human studies indicate adequate exposure for the desired pharmacotherapeutic effects and tolerability.

If a medicine is selected for the PRIME scheme, the EMA:

• appoints a rapporteur from the CHMP or from the CAT to provide continuous support and to build up knowledge of the medicine in advance of the filing of an MMA;

• appoints a rapporteur from the CHMP or from the CAT to provide continuous support and to build up knowledge of the medicine in advance of the filing of an MAA;

• issues guidance on the applicant’s overall development plan and regulatory strategy;

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Where, during the course of development, a medicine no longer meets the eligibility criteria, or if a medicine granted early access to the PRIME scheme cannot later demonstrate proof of concept, support under the PRIME scheme may be withdrawn.

Approval of other therapies for the treatment Friedreich’s ataxia, including the approval of omaveloxolone could negatively impact our continued access to this and similar programs.

Loss of PRIME designation for nomlabofusp or the failure to obtain such designation for any future product candidates could adversely affect our business, financial condition and results of operation.

Approval of other therapies for the treatment of FA, including the approval of omaveloxolone could negatively impact our continued access to this and similar programs.

Changes in regulatory requirements, FDA guidance, guidance from other regulatory authorities or unanticipated events during our non-clinical or clinical trials of nomlabofusp or future product candidates may result in changes to clinical trial protocols or additional non-clinical or clinical trial requirements, which could result in increased costs to us and could delay our development timeline.

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Amendments to our clinical trial protocols would require resubmission to the FDA, or the applicable regulatory authorities as well as IRBs and ethics committees for review and approval, which may adversely impact the cost, timing or successful completion of a clinical trial.

If we experience delays completing, or if we terminate, any of our clinical trials, or if

we are required to conduct additional clinical trials, or non-clinical studies and/or post-market studies, the commercial prospects for nomlabofusp or any other potential product candidates may be harmed and our ability to generate product revenue will be delayed or eliminated, and it would materially adversely affect our business, financial condition and results of operations.

If we experience delays completing, or if we terminate, any of our clinical trials, or if we are required to conduct additional clinical trials, or non-clinical studies and/or post-market studies, the commercial prospects for nomlabofusp or any other potential product candidates may be harmed and our ability to generate product revenue will be delayed or eliminated, and it would materially adversely affect our business, financial condition and results of operations.

In order to market any product outside of the United States, we must comply with numerous and varying regulatory requirements of other countries regarding drug development and commercialization.

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Even if we receive marketing approval for nomlabofusp in the United States, we may never receive regulatory approval to market nomlabofusp outside of the United States.

Changes in the FDA, other government agencies or comparable regulatory authorities could hinder their ability to hire and retain key leadership and other personnel, prevent new products and services from being developed, approved or commercialized in a timely manner or otherwise prevent those agencies from performing normal business functions on which the operation of our business may rely, which could negatively impact our business.

Changes in funding or disruptions at the FDA, the SEC, patent offices in the United States and abroad and other government agencies caused by funding shortages or global health concerns could hinder their ability to hire and retain key leadership and other personnel, or otherwise prevent new or modified products from being developed, approved or commercialized in a timely manner or at all, or otherwise prevent those agencies from performing normal business functions on which the operation of our business may rely, which could negatively impact our business.

The current administration is focused on reducing costs of the federal government generally, including significantly reducing the number of government employees.

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government has shut down several times and certain regulatory agencies, such as the FDA and the SEC have had to furlough critical employees and stop critical activities.

If a prolonged government shutdown occurs, including as a result of reaching the debt ceiling, if the FDA or SEC experiences significant decreases in funding or personnel it could significantly impact the ability of the FDA or other regulatory authorities to timely review and process our regulatory submissions, which could have a material adverse effect on our business and our timelines.

If a prolonged government shutdown occurs, such as the one that occurred in October 2025, including as a result of reaching the debt ceiling, if the FDA or SEC experiences significant decreases in funding or personnel it could significantly impact the ability of the FDA or other regulatory authorities to timely review and process our regulatory submissions, which could have a material adverse effect on our business and our timelines.

Further, government shutdowns could impact our ability to access the public markets and obtain additional capital in the future.

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Legislative and regulatory proposals have been made to expand post-approval requirements and restrict sales and promotional activities for pharmaceutical products.

We cannot be sure whether additional legislative changes will be enacted, or whether FDA regulations, guidance or interpretations will be changed, or what the impact of such

changes on the marketing approvals of our product candidates, if any, may be.

We cannot be sure whether additional legislative changes will be enacted, or whether FDA regulations, guidance or interpretations will be changed, or what the impact of such changes on the marketing approvals of our product candidates, if any, may be.

In addition, increased scrutiny by the U.S.

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We have not obtained regulatory approval for nomlabofusp, and it is possible that this product candidate or any product candidates we may seek to develop in the future will never obtain regulatory approval.

If marketing approval is obtained, it will likely include post-marketing studies, and other post-marketing requirements, and surveillance such as REMS which will require the expenditure of substantial resources beyond the proceeds we currently have on hand.

If marketing approval is obtained, it will likely include post-marketing studies, and other post-marketing requirements, and could include surveillance such as REMS which will require the expenditure of substantial resources beyond the proceeds we currently have on hand.

Furthermore, we are not permitted to market nomlabofusp in the United States, or the European Union until we receive approval of a BLA from the FDA or the grant of an MA from the European Commission, or in any other foreign countries until we receive the requisite marketing approval from such countries.

The development of drugs for FA or other rare diseases may require initial non-clinical studies, early and usually smaller, clinical trials and randomized, double-blind placebo controlled long-term safety and efficacy trials in order to test the safety and efficacy of the drug.

Nomlabofusp requires substantial further clinical development before we can submit a BLA to the FDA.

Development and/or regulatory programs for nomlabofusp in any countries other than the United States (such as a MAA to the EMA) are only in very preliminary stages and may require substantial further development in those countries prior to regulatory submissions seeking regulatory approval for marketing.

Development and/or regulatory programs for nomlabofusp in countries (such as a MAA to the EMA) are in earlier stages than in the United States and may require substantial further development in those countries prior to regulatory submissions seeking regulatory approval for marketing.

Even after successful completion of clinical trials, there is a risk that the FDA or other regulatory agencies may request further information from us, disagree with our findings or otherwise undertake a lengthy review of our submission.

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If our operations, including anticipated activities to be conducted by our sales team, were found to be in violation of any of these laws or any other governmental regulations that may apply to us, we may be subject to significant civil, criminal and administrative penalties, damages, fines and exclusion from government funded healthcare programs, such as Medicare and Medicaid, any of which could substantially disrupt our operations and would materially adversely affect our business, financial condition and results of operations.

exclusions from government funded healthcare programs, which could have a material adverse effect on our business, results of operations, financial condition and prospects.

If any of the physicians or other providers or entities with whom we expect to do business is found not to be in compliance with applicable laws, they may be subject to criminal, civil or administrative sanctions, including exclusions from government funded healthcare programs, which could have a material adverse effect on our business, results of operations, financial condition and prospects.

Healthcare legislation, including potentially unfavorable pricing regulations or other healthcare reform initiatives may increase the difficulty and cost for us to obtain marketing approval of and commercialize our product candidates.

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Previously, in March 2010, the ACA was enacted, which was intended to broaden access to health insurance, reduce or constrain the growth of healthcare spending, enhance remedies against fraud and abuse, add new transparency requirements for health care and health insurance industries, impose new taxes and fees on the health industry and impose additional health policy reforms.

Healthcare reform initiatives recently culminated in the enactment of the IRA, which, among other things, allow allows HHS to directly negotiate the ceiling price of a statutorily specified number of drugs and biologic each year that CMS reimburses under Medicare Part B and Part D, requires the payment of rebates on Medicare Part B and Part D drugs whose prices have increased at a rate faster than the rate of inflation, and redesign the Medicare Part D cost sharing structure, including revising manufacturer financial liability for covered products.

Healthcare reform initiatives culminated in the enactment of the IRA, which, among other things, allows HHS to directly negotiate the ceiling price of a statutorily specified number of drugs and biologic each year that CMS reimburses under Medicare Part B and Part D, requires the payment of rebates on Medicare Part B and Part D drugs whose prices have increased at a rate faster than the rate of inflation, and redesign the Medicare Part D cost sharing structure, including revising manufacturer financial liability for covered products.

For more information, see the section of this report titled “Business – Healthcare Laws and Regulations – Healthcare Reform.” Moreover, the Creating and Restoring Equal Access to Equivalent Samples Act (“CREATES” Act), was enacted in 2019 requiring sponsors of approved new drug applications and biologics license applications to provide sufficient quantities of product samples on commercially reasonable, market-based terms to entities developing generic drugs and biosimilar biological products.

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We expect that additional federal, state and foreign healthcare reform measures will be adopted in the future, any of which could limit the amounts that federal and state governments will pay for healthcare products and services, which could result in limited coverage and reimbursement and reduced demand for our products, once approved, or additional pricing pressures.

The effect of these healthcare reform initiatives on our business and the pharmaceutical industry in general is not yet known, but could be substantial and materially adverse to our ability to successfully commercialize our product candidates at profitable price points.

Even if approved, reimbursement policies could limit our ability to sell product candidates that we elect to sell on our own.

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In some foreign countries, particularly in Canada and European countries, the pricing of prescription pharmaceuticals is subject to strict governmental control.

In these countries, pricing negotiations with governmental authorities can take six to 12 months or longer after the receipt of regulatory approval and product launch.

In these countries, pricing negotiations with governmental authorities can take 6 to 12 months or longer after the receipt of regulatory approval and product launch.

favorable reimbursement for the indications sought or pricing approval in some countries, we may be required to conduct a clinical trial that compares the cost-effectiveness of product candidates that we elect to sell on our own with other available therapies.

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The FDA has also requested that companies enter into consent decrees or permanent injunctions under which specified promotional conduct is changed or curtailed.

Further, FDA’s Office of Prescription Drug Promotion (OPDP) actively scrutinizes promotional communications, including digital and social media;

any materials that are false, misleading or promote unapproved uses can lead to enforcement actions and could necessitate corrective communications.

In the current administration, the FDA has increased its enforcement scrutiny over prescription drug advertising, particularly direct-to-consumer product promotion and advertising.

If the FDA finds any of our promotional communications or advertising to be violative, we may receive an untitled or warning letter, requests for corrective advertising, or fines, amongst other enforcement tools available to the FDA.

If we cannot successfully manage the promotion of nomlabofusp or any potential product candidates, if approved, we could become subject to significant liability, which would materially adversely affect our business, financial condition and results of operations.

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If these or other companies enact pricing strategies that impact the price we can charge for our product candidate, if approved, we may reduce our prices and our revenue and results of operations could be affected.

Any new product could also affect our ability to recruit and retain clinical trial patients, to obtain and maintain designations or eligibility for expedited regulatory pathways, and to commercialize current and future product candidates.

Given that we are still in a relatively early phase of development for nomlabofusp, the recent approval and commercialization of omaveloxolone and the approval of any future competing technologies could provide competitors with a significant competitive advantage and may create an additional barrier to market acceptance of nomlabofusp.

Any new product could also affect our ability to recruit and retain clinical trial patients, to obtain and maintain designations or eligibility for expedited regulatory pathways, and

to commercialize current and future product candidates.

Given our phase of development for nomlabofusp, the recent approval and commercialization of omaveloxolone and the approval of any future competing technologies could provide competitors with a significant competitive advantage and may create an additional barrier to market acceptance of nomlabofusp.

If we are not able to compete effectively against our current and future competitors, our business will not grow and our financial condition and results of operations will be adversely affected.

Mergers and acquisitions in the pharmaceutical and biotechnology industries may result in even more resources being concentrated among a smaller number of our competitors.

Smaller or early-stage companies may

also prove to be significant competitors, particularly through collaborative arrangements with large and established companies.

Smaller or early-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established companies.

These competitors also compete with us in recruiting and retaining qualified scientific and management personnel and establishing clinical trial sites and patient registration for clinical trials, as well as in acquiring technologies complementary to, or necessary for, our programs.

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We may not be able to attract and retain quality personnel on acceptable terms, or at all.

In addition, to the extent we hire personnel from competitors, we may be

subject to allegations that they have been improperly solicited or that they have divulged proprietary or other confidential information, or that their former employers own their research output.

In addition, to the extent we hire personnel from competitors, we may be subject to allegations that they have been improperly solicited or that they have divulged proprietary or other confidential information, or that their former employers own their research output.

We rely on consultants and advisors, including scientific, non-clinical, manufacturing and clinical advisors, to assist us in formulating our development and commercialization strategy.

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Those factors may include the design or results of clinical trials, the likelihood of approval by the FDA or similar regulatory authorities outside the United States, the potential market for the applicable product candidate, the costs and complexities of manufacturing and delivering such product candidate to patients, the potential of competing products, the existence of uncertainty with respect to our ownership of technology, which can exist if there is a challenge to such ownership without regard to the merits of the challenge and industry and market conditions generally.

The collaborator may also

consider alternative product candidates or technologies for similar indications that may be available to collaborate on and whether such collaboration could be more attractive than the one with us for our product candidate.

The collaborator may also consider alternative product candidates or technologies for similar indications that may be available to collaborate on and whether such collaboration could be more attractive than the one with us for our product candidate.

The terms of any collaboration or other arrangement that we may establish may not be favorable to us.

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and other adverse business consequences.

In the ordinary course of business, we collect, receive, store, process, generate, use, transfer, disclose, make accessible, protect, secure, dispose of, transmit, and share (collectively, process) personal data and other sensitive information, including proprietary and confidential business data, trade secrets, intellectual property, data we collect about trial participants in connection with clinical trials, sensitive third-party data, business plans, transactions, financial information and medical information collected by our patient access management team (collectively,

sensitive data).

Our data processing activities may subject us to numerous data privacy and security obligations, such as various laws, regulations, guidance, industry standards, external and internal privacy and security policies, contractual requirements, and other obligations relating to data privacy and security.

In the United States, federal, state, and local governments have enacted numerous data privacy and security laws, including data breach notification laws, personal data privacy laws, consumer protection laws (e.g., Section 5 of the Federal Trade Commission Act), and other similar laws (e.g., wiretapping laws).

In the United States, federal, state, and local governments have enacted numerous data privacy and security laws, including data breach notification laws, personal data privacy laws, consumer protection laws (e.g., Section 5 of the Federal Trade Commission Act (FTCA)), and other similar laws (e.g., wiretapping laws).

For example, HIPAA, as amended by HITECH, imposes specific requirements relating to the privacy, security, and transmission of individually identifiable health information.

Even when HIPAA does not apply, according to the FTC, failing to take appropriate steps to keep consumers’ personal information secure constitutes unfair acts or practices in or affecting commerce in violation of the FTCA.

The FTC’s current guidance for appropriately securing consumers’ personal information is similar to what is required by the HIPAA security regulations, but this guidance may change in the future, resulting in increased complexity and the need to expend additional resources to ensure we are complying with the FTCA.

Additionally, in the past few years, numerous U.S.

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comprehensive privacy laws exempt some data processed in the context of clinical trials, these laws may increase compliance costs and potential liability with respect to other personal data we may maintain about California residents.

Similar laws are being considered in several other states, as well as at the federal and local levels, and we expect more jurisdictions to pass similar laws in the future.

Similar laws are being considered in

several other states, as well as at the federal and local levels, and we expect more jurisdictions to pass similar laws in the future.

Furthermore, other states have proposed or enacted legislation that is focused on more narrow aspects of privacy.

For example, some states have passed laws that protect biometric information and a smaller number of states have passed or are considering laws that are specifically focused upon health privacy, such as Washington’s My Health My Data Act.

The My Health My Data Act imposes new state restrictions and requirements on the processing and sale of consumer health data and creates a private right of action, which further increases the relevant compliance risk.

Connecticut and Nevada have also passed similar laws regulating consumer health data.

The effects of state and federal privacy laws are potentially significant and may require us to modify our data processing practices and policies and to incur substantial costs and potential liability in an effort to comply with such legislation.

Outside the United States, an increasing number of laws, regulations, and industry standards may govern data privacy and security.

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13,709/2018), and China’s Personal Information Protection Law (PIPL) impose strict requirements for processing personal data.

For example, the GDPR includes obligations requiring disclosures to individuals regarding data processing activities, requiring that safeguards are implemented to protect the security and confidentiality of personal data, limiting retention periods for personal data, creating mandatory data breach notification requirements in certain circumstances, and requiring that certain measures (including contractual requirements) are put in place when engaging third-party processors Companies that fail to comply with the GDPR may face temporary or definitive bans on data processing and other corrective actions;

For example, the GDPR imposes numerous obligations on companies, including requirements relating to processing health and other sensitive data, where required obtaining consent of the individuals to whom the personal data relates, having legal bases and/or conditions for processing, requiring disclosures to individuals regarding data processing activities, requiring that safeguards are implemented to protect the security and confidentiality of personal data, responding on individuals’ requests to exercise their rights, limiting retention periods for personal data, creating mandatory data breach notification requirements in certain circumstances, requiring that certain measures (including contractual requirements) are put in place when engaging third-party processors, appointing data protection officers, conducting data protection impact assessments, ensuring certain accountability measures are in place and record keeping.

Companies that fail to comply with the GDPR may face temporary or definitive bans on data processing and other corrective actions;

fines of up to 20 million Euros under the EU GDPR / 17.5 million pounds sterling under the UK GDPR or 4% of annual global revenue, whichever is greater;

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Companies must comply with the revised version of the FADP and its revised ordinances from September 1, 2023, which may result in an increase of costs of compliance, risks of noncompliance and penalties for noncompliance.

In addition, we may be unable to transfer personal data from Europe and other jurisdictions to the United States or other countries due to data localization requirements or limitations on cross-border data flows.

Europe and other jurisdictions have enacted laws requiring data to be localized or limiting the transfer of personal data to other countries.

In particular, the European Economic Area (EEA) and the UK have significantly restricted the transfer of personal data to countries whose privacy laws it believes are inadequate, including the United States in certain circumstances, unless a derogation exists or adequate international transfer safeguards are put in place (for example, the European Commission approved Standard Contractual Clauses, and the UK International Data Transfer Agreement/Addendum) and transfer impact assessments carried out.

Although the UK is regarded as a third country under the EU GDPR, the EC has now issued a decision recognizing the UK as providing adequate protection under the EU GDPR and, therefore, transfers of personal data originating in the EU to the UK remain unrestricted.

In December 2025, the EC adopted a decision to extend the validity of the UK adequacy decision for six years until December 2031, determining that the UK continues to offer a level of data protection that is “essentially equivalent” to the EU standards.

This follows the UK’s adoption of the Data (Use and Access) Act 2025 (the “DUAA”) on 19 June 2025.

The respective provisions and enforcement of the EU GDPR and UK GDPR may further diverge in the future and create additional regulatory challenges and uncertainties.

This lack of clarity on future UK laws and regulations and their interaction with EU laws and regulations could add legal risk, complexity and cost to our handling of personal data and our privacy and data security compliance programs and could require us to implement different compliance measures for the UK and the EEA.

Like the EU GDPR, the UK GDPR restricts personal data transfers outside the UK to countries not regarded by the UK as providing adequate protection.

The UK government has confirmed that personal data transfers from the UK to the European Economic Area (EEA) remain free flowing.

In addition, to enable the transfer of personal data outside of the EEA or the UK, adequate safeguards must be implemented in compliance with European and UK data protection laws.

There are currently various mechanisms that may be used to transfer personal data from the EEA and UK to the United States in compliance with law, such as the EEA’s standard contractual clauses, the UK’s International Data Transfer Agreement / Addendum, and the EU-U.S.

Data Privacy Framework (“Framework”) and the UK extension thereto (which allows for transfers to relevant U.S.-based organizations who self-certify compliance and participate in the Framework).

When relying on certain mechanisms, such as the EEA’s standard contractual clauses, companies are required to conduct transfer

impact assessments.

Other jurisdictions may adopt similarly stringent interpretations of their data localization and cross-border data transfer laws.

significant expense, increased exposure to regulatory actions, substantial fines and penalties, the inability to transfer data and work with partners, vendors and other third parties, and injunctions against our processing or transferring of personal data necessary to operate our business.

Furthermore, regulators and legislators in the U.S.

are increasingly scrutinizing and restricting certain personal data transfers and transactions involving foreign countries.

For example, Executive Order 14117, Preventing Access to Americans’ Bulk Sensitive Personal Data and United States Government-Related Data by Countries of Concern, as implemented by Department of Justice regulations issued in December 2024, prohibits data brokerage transactions involving certain sensitive personal data categories, including health data, genetic data, and biospecimens, to countries of concern, including China.

The regulations also restrict certain investment agreements, employment agreements and vendor agreements involving such data and countries of concern, absent specified cybersecurity controls.

Actual or alleged violations of these regulations may be punishable by criminal and/or civil sanctions and may result in exclusion from participation in federal and state programs.

If we are unable to transfer personal data from the EEA, the UK, or other jurisdictions to the United States, or if the requirements for a legally-compliant transfer are too onerous, we could face significant adverse consequences, including by limiting our ability to conduct clinical trial activities in Europe and elsewhere, the interruption or degradation of our operations, the need to relocate part of or all of our business or data processing activities to other jurisdictions (such as Europe) at significant expense, increased exposure to regulatory actions, substantial fines and penalties, the inability to transfer data and work with partners, vendors and other third parties, and injunctions against our processing or transferring of personal data necessary to operate our business.

In addition to data privacy and security laws, we may be contractually subject to industry standards adopted by industry groups and may become subject to such obligations in the future.

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Our internal computer systems, as well as those of CROs, CMOs, vendors, contractors, and consultants, and potential collaborators may experience failures, unauthorized access, or security breaches, potentially causing a material disruption in our product development programs, operations, harm to our brand, significant liabilities, loss of revenue, and additional costs.

Despite implementing comprehensive security measures, both our internal computer systems and those of our contracted third-party service providers are susceptible to various threats, including cyber-attacks, computer viruses, unauthorized access, natural disasters, terrorism, war, and telecommunication and electrical failures.

Despite implementing security measures, both our internal computer systems and those of our contracted third-party service providers are susceptible to various threats, including cyber-attacks, data breaches, ransomware, social engineering (including phishing), computer viruses, unauthorized access, natural disasters, terrorism, war, and telecommunication and electrical failures.

The extensive use of mobile devices accessing confidential information further heightens the risks, leading to potential device loss, security incidents, and data breaches that could result in the loss of confidential information and intellectual property.

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For instance, the loss of clinical trial data from completed trials could lead to delays in regulatory approval efforts and significantly increase costs for data recovery or reproduction.

We are exposed to risks stemming from misappropriation, misuse, leakage, falsification, or intentional or accidental release or loss of information maintained in our information systems and networks, including personal

information of our employees.

External parties may attempt to penetrate our systems or induce our employees or those of our vendors to disclose sensitive information.

As with other companies, we face threats to our data and systems, including malicious codes, viruses, and cyber-attacks.

As with other companies in our industry, we face threats to our data and systems, including malicious codes, data breaches, ransomware, social engineering (including phishing), viruses, and cyber-attacks.

The increasing number and complexity of these threats over time pose a challenge.

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In our endeavor to protect systems storing critical information, we have implemented security measures.

However, given their size and complexity and the increasing amounts of information maintained, these systems, including our internal information technology systems and those of third-party entities like Contract Research Organizations, Contract Manufacturing Organizations, contractors, and consultants, remain potentially vulnerable to breakdowns, interruptions, and security breaches.

However, given their size and complexity and the increasing amounts of information maintained, these systems, including our internal information technology systems and those of third-party entities like CROs, CMOs, contractors, and consultants, remain potentially vulnerable to breakdowns, interruptions, and security breaches.

Incidents such as service interruptions, system malfunctions, natural disasters, terrorism, war, telecommunication, and electrical failures, as well as security breaches from inadvertent or intentional actions by employees, contractors, consultants, and other third parties, including cyber-attacks by malicious entities, may compromise our system infrastructure.

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During times of war and other major conflicts, we and the third parties upon which we rely may be vulnerable to a heightened risk of these attacks, including retaliatory cyber-attacks, that could materially disrupt our systems and operations, supply chain, and ability to produce, sell and distribute our goods and services.

software or hardware failures, loss of data or other information technology assets, adware, attacks enhanced or facilitated by AI, telecommunications failures, earthquakes, fire, flood, and other similar threats.

We and the third parties upon which we rely are subject to a variety of evolving threats, including but not limited to, social engineering attacks (including through deep fakes, which may be increasingly more difficult to identify as fake, and phishing attacks), malicious code (such as viruses and worms), malware (including as a result of advanced persistent threat intrusions), denial-of-service attacks, credential stuffing, credential harvesting, personnel misconduct or error, ransomware attacks, supply-chain attacks, software bugs, server malfunction, software or hardware failures, loss of data or other information technology assets, adware, attacks enhanced or facilitated by Artificial Intelligence (“AI”), telecommunications failures, earthquakes, fire, flood, and other similar threats.

Ransomware attacks, including by organized criminal threat actors, nation-states, and nation-state-supported actors, are becoming increasingly prevalent and severe and can lead to significant interruptions, delays, or outages in our operations, disruption of clinical trials or otherwise affecting our ability to provide our products or product candidates, loss of sensitive data (including data related to clinical trials) and income, significant extra expenses to restore data or systems, reputational harm and the diversion of funds.

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Vulnerabilities could be exploited and result in a security incident.

Any of the previously identified or similar threats could cause a security incident or other interruption that could result in unauthorized, unlawful, or accidental acquisition, modification, destruction, loss, alteration, encryption, disclosure of, or access to our sensitive information or our information technology systems, or those of the third parties upon whom we rely.

the third parties upon whom we rely.

A security incident or other interruption could disrupt our ability (and that of third parties upon whom we rely) to provide our products.

We may expend significant resources or fundamentally change our business activities and practices (including our clinical trials) to try to protect against security incidents.

We may expend significant resources or fundamentally change our business activities and practices (including our clinical trials) in an effort to protect against security incidents.

Certain data privacy and security obligations may require us to implement and maintain specific security measures or industry-standard or reasonable security measures to protect our information technology systems and sensitive data.

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In addition to experiencing a security incident, third parties may gather, collect, or infer sensitive data about us from public sources, data brokers or other means that reveals competitively sensitive details about our organization and could be used to undermine our competitive advantage or market position.

Additionally, sensitive information of the Company could be leaked, disclosed, or revealed as a result of or in connection with the use of generative AI technologies.

Additionally, sensitive information could be leaked, disclosed, or revealed as a result of or in connection with the use of generative AI technologies.

Our contracts may not contain limitations of liability, and even where they do, there can be no assurance that limitations of liability in our contracts are sufficient to protect us from liabilities, damages, or claims related to our data privacy and security obligations.

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Employees or contractors may use unauthorized or unapproved software, cloud services, or personal devices to access, store, or transmit company data, a practice commonly referred to as “Shadow IT”.

The use of such unapproved technologies increases security risks, as these applications and services may not adhere to our established cybersecurity and compliance standards.

The use of such unapproved technologies increases security risks, as these applications and services may not adhere to our

established cybersecurity and compliance standards.

Shadow IT may introduce vulnerabilities, expose sensitive data to unauthorized parties, or lead to misconfigurations that may increase the likelihood of cyberattacks or data breaches.

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If we cannot successfully defend ourselves against product liability claims, we may incur substantial liabilities or be required to stop development or, if approved, limit commercialization of our product candidates.

Any such product liability claims

may include allegations of defects in manufacturing, defects in design, a failure to warn of dangers inherent in the product, including as a result of interactions with alcohol or other drugs, negligence, strict liability and a breach of warranties.

Any such product liability claims may include allegations of defects in manufacturing, defects in design, a failure to warn of dangers inherent in the product, including as a result of interactions with alcohol or other drugs, negligence, strict liability and a breach of warranties.

Claims could also be asserted under consumer protection acts in other jurisdictions.

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Large judgments have been awarded in class action lawsuits based on drugs that had unanticipated side effects.

The cost of any product liability litigation or other proceedings, even if resolved in our favor, could be substantial, particularly in light of the size of our business and financial resources.

The cost of any product liability litigation or other proceedings, even if resolved in our favor, could be substantial, particularly in light of the size of our business and financial

A product liability claim or series of claims brought against us could cause our stock price to decline and, if we are unsuccessful in defending such a claim or claims and the resulting judgments exceed our insurance coverage, our financial condition, business, results of operations and prospects could be materially adversely affected.

Artificial intelligence presents risks and challenges that can impact our business, including by posing security risks to our confidential information, proprietary information and personal data.

Issues in the development and use of AI, combined with an uncertain regulatory environment, may result in reputational harm, liability, or other adverse consequences to our business operations.

As with many technological innovations, AI presents risks and challenges that could impact our business.

We expect to see increasing government and supranational regulation related to AI use and ethics, which may also significantly increase the burden and cost of research, development and compliance in this area.

For example, the EU’s Artificial Intelligence Act (“AI Act”) — the world’s first comprehensive AI law – which has entered into force on August 1, 2024 and most provisions of which will become effective on August 2, 2026.

This legislation imposes significant obligations on providers and deployers of high risk AI systems, and encourages providers and deployers of AI systems to account for EU ethical principles in their development and use of these systems.

If we develop or use AI systems that are governed by the AI Act, it may necessitate ensuring higher standards of data quality, transparency, and human oversight, as well as adhering to specific and potentially burdensome and costly ethical, accountability, and administrative requirements.

Furthermore, in the U.S., a number of states have proposed and passed laws regulating various uses and aspects of AI, and federal regulators have issued guidance affecting the use of AI in regulated sectors.

We may adopt and integrate generative AI tools into our systems.

Our vendors may also incorporate generative AI tools into their offerings, and the providers of these generative AI tools and our use of such tools may not meet existing or rapidly evolving regulatory or industry standards.

If we, our vendors, or our third-party partners experience an actual or perceived breach or privacy or security incident because of the use of generative artificial intelligence, we may lose valuable intellectual property and confidential information and our reputation and the public perception of the effectiveness of our security measures could be harmed.

Further, bad actors around the world use increasingly sophisticated methods, including the use of AI to engage in illegal activities involving the theft and misuse of personal information, confidential information, and intellectual property.

Any of these outcomes could damage our reputation, result in the loss of valuable property and information, and adversely impact our business.

Risks Related to Our Reliance on Third Parties

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As a result, many important aspects of our drug development programs are outside of our direct control.

We have limited experience in conducting or supervising clinical trials that must be performed to obtain data to submit in concert with applications for approval by the FDA, the EMA or other comparable foreign regulatory authorities.

As a company, we have limited experience in conducting or supervising clinical trials that must be performed to obtain data to submit in concert with applications for approval by the FDA, the EMA or other comparable foreign regulatory authorities.

As a result, we expect to continue to rely on CROs, clinical trial sites, clinical data management organizations and consultants to design, conduct, supervise and monitor our non-clinical studies and clinical trials.

We, our CROs, and contractors are required to comply with various regulations, including the FDA’s regulations regarding current Good Clinical Practices (“cGCPs”) which are enforced by regulatory agencies, including the FDA, and comparable foreign regulatory authorities to ensure the health, safety and rights of patients are protected in clinical development and clinical trials, and that trial data integrity is assured.

Regulatory authorities ensure compliance with these requirements through periodic inspections of trial sponsors, principal investigators and

clinical trial sites.

Regulatory authorities ensure compliance with these requirements through periodic inspections of trial sponsors, principal investigators and clinical trial sites.

Our expected reliance on third parties that we do not control does not relieve us of these responsibilities and requirements.

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These agreements typically limit the rights of the third parties to use or disclose our confidential information, such as trade secrets, intellectual property, data from clinical studies and future development plans.

Despite the contractual provisions employed when working with third parties, the need to share confidential information increases the risk that such confidential information become known by our competitors, are inadvertently incorporated into the technology of others, or are disclosed or used in violation of these agreements.

incorporated into the technology of others, or are disclosed or used in violation of these agreements.

Given that our proprietary position is based, in part, on our confidential information, a competitor’s discovery of our confidential information or other unauthorized use or disclosure would impair our competitive position and may have an adverse effect on our business.

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Though we carefully manage our relationships with CROs, and contractors there can be no assurance that we will not encounter similar challenges or delays in the future or that these delays or challenges will not have a material adverse impact on our business, financial condition, results of operation and prospects.

We rely on third-party supply and manufacturing partners for drug supplies for our research and development, non-clinical activities, and clinical activities, and may do the same for any commercial supplies of our product candidates.

We have not yet manufactured or formulated nomlabofusp or any other product candidate on a commercial scale and may not be able to do so for any of our product candidates.

We rely on supply and manufacturing partners for drug supplies for our research and development, non-clinical activities, and clinical activities, and plan to do the same for any commercial supplies of our product candidates.

We rely on third-party supply and manufacturing partners to supply the materials and components for, and manufacture, our research and development, non-clinical and clinical study drug substance and drug product.and third parties to provide ancillary supplies that may be associated with dosing nomlabofusp in clinical trials and commercially.

Furthermore, regulatory requirements for these materials, components and ancillary supplies may be different in different jurisdictions which could affect supply availability and our ability to conduct our clinical trials or supply commercial product.

We have not yet manufactured or formulated nomlabofusp or any other product candidate on a full commercial scale and may not be able to do so for any of our product candidates.

We will work to develop and optimize our manufacturing process;

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We do not own manufacturing facilities or supply sources for such components, non-clinical and clinical study drug substance, product and materials, including devices that may be required for administration, but may develop these capabilities in the future.

There can be no assurance that our supply of research and development, non-clinical and clinical development of drugs and other materials will not be limited, interrupted, restricted in certain geographic regions or will be of satisfactory quality or continue to be available at acceptable prices.

Adequate sources may be limited and there can be no assurance that our supply of research and development, non-clinical and clinical development of drugs and other materials will not be limited, interrupted, restricted in certain geographic regions or will be of satisfactory quality or continue to be available at acceptable prices.

In particular, replacement of any product formulation manufacturer we may engage could require significant effort and expertise because there may be a limited number of qualified replacements.

For example, we rely and expect to continue to rely on a small number of manufacturers to supply us with our requirements for drug substance and formulated drug product related to our nomlabofusp clinical program.

The drug substance which is in frozen liquid form for nomlabofusp is currently manufactured for us by a third-party manufacturer, and the frozen liquid form of drug product is made at another manufacturer.

We are undertaking a program with a third party manufacturer to begin to produce a lyophilized version of the drug product from the same drug substance, that, once available, we intend to use in certain of our future planned clinical trials.

The drug substance for nomlabofusp is currently manufactured for us by a third-party manufacturer, and the drug product is made at another manufacturer.

Our research and development programs could be adversely affected by a significant interruption in these manufacturing services or in the supply of drug substance and formulated drugs.

In addition, because we rely on multiple manufacturers for our nomlabofusp clinical program, termination of our agreements with any of these manufacturers could significantly adversely impact our current and planned operations.

In addition, because we rely on multiple manufacturers for our nomlabofusp clinical program, and planned commercial activities if nomlabofusp is approved, and termination of our agreements with any of these manufacturers could significantly adversely impact our current and planned operations.

In the event that any of our suppliers or manufacturers fails to perform their obligations to us in relation to quality, timing or otherwise, or if our supply of components or other materials becomes limited or interrupted for other reasons, we may be forced to manufacture the materials ourselves, for which we currently do not have the capabilities or resources, or enter into an agreement with another third party, which we may not be able to do on reasonable terms, if at all.

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These factors would increase our reliance on such manufacturer or require us to obtain a license from such manufacturer in order to have another third party manufacture our product candidates.

If we are required to change manufacturers for any reason, we will be required to verify that the new manufacturer maintains facilities and procedures that comply with quality standards and with all applicable regulations and guidelines.

The delays associated with the verification of a new manufacturer could negatively affect our ability to develop product candidates in a timely manner or within budget.

We also rely on third parties to store master and working cell banks.

We currently have one master cell bank and one working cell bank for nomlabofusp and believe we would have adequate backup should any cell bank be lost in a catastrophic event.

However, it is possible that we could lose multiple cell banks and have our manufacturing severely impacted by the need to replace the cell banks, which could materially and adversely affect our business, financial condition and results of operations.

We currently have one master cell bank which is stored at two different locations.

However, if we should lose the master cell bank at both sites, our manufacturing would be severely impacted by the need to replace the master cell bank, which could materially and adversely affect our business, financial condition and results of operations.

We may rely on third party manufacturers if we receive regulatory approval for any product candidate.

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If we are unable to obtain or maintain third party manufacturing for product candidates, or to do so on commercially reasonable terms, we may not be able to develop and commercialize our product candidates successfully.

Our or a third party’s failure to execute on our

manufacturing requirements could adversely affect our business, financial condition and results of operations in a number of ways, including:

Our or a third party’s failure to execute on our manufacturing requirements could adversely affect our business, financial condition and results of operations in a number of ways, including:

• an inability to initiate or continue clinical trials of product candidates under development;

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• requirements to cease distribution or to recall batches of our product candidates;

• in the event of approval to market and commercialize a product candidate, an inability to meet commercial demands for our products.

• in the event of approval to market and commercialize a product candidate, an inability to successfully further scale up manufacturing capacity and meet commercial demands for our products.

We and our contract manufacturers are subject to significant regulation with respect to manufacturing our products.

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This could delay completion of clinical trials, require the conduct of bridging clinical trials or the repetition of one or more clinical trials, increase clinical trial costs, delay approval of our product candidates and jeopardize our ability to commercialize our product candidates and generate revenue.

Our contract manufacturers may be unable to successfully scale up manufacturing of our product candidate in sufficient quality or quantity in a timely manner, if at all, which may impair the clinical advancement and commercialization of our product candidate.

In order to conduct clinical trials of our product candidate and commercialize our product candidate, if approved, our contract manufacturers need to manufacture them in large quantities.

We have no experience manufacturing, or managing third parties in manufacturing, our product candidate in the volumes that will be necessary to support large-scale clinical trials or, if approved, commercial sales.

Efforts to establish these capabilities may not meet initial expectations as to scheduling, scale-up, reproducibility, yield, purity, cost, potency or quality.

If our contract manufacturers are unable to successfully scale up the manufacture of our product candidate in sufficient quality and quantity in a timely manner, the development, testing and clinical trials of our product candidate may be delayed or infeasible, and regulatory approval or, if approved, commercial launch and sustained commercialization of our product candidate may be delayed or not obtained, which could significantly harm our business, financial condition and results of operations.

Supply sources could be interrupted from time to time and, if interrupted, would disrupt our contract manufacturers’ ability to manufacture our product candidate at the scale required.

Our reliance on contract manufacturers may adversely affect our operations or result in unforeseen delays or other problems beyond our control.

Because of contractual restraints and the limited number of third-party manufacturers with the expertise, required regulatory approvals and facilities to manufacture our product

candidate on a commercial scale, replacement of a manufacturer may be expensive and time consuming and may cause interruptions in the production of our product candidate.

A third-party manufacturer may also encounter difficulties in production.

These problems may include:

• failure to comply with strictly enforced federal, state and foreign regulations (including facilities inspections by regulatory authorities) that vary in each country;

• difficulties with production costs, scale-up and yields;

• unavailability of raw materials and supplies;

• insufficient quality control and assurance;

• shortage of qualified personnel;

• lack of capital funding.

If we are unable to meet the clinical or, if approved, commercial supply need for our product candidate, or to do so on commercially reasonable terms, we may not be able to further develop our product candidate, including meeting all regulatory requirements, and commercialize our product candidate successfully.

We enter into various contracts in the normal course of our business in which we indemnify the other party to the contract.

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If we do not adequately protect our intellectual property and proprietary technology, competitors may be able to use our technologies and erode or negate any competitive advantage we may have, which could harm our business and ability to achieve profitability.

With respect to our patent portfolio, we in-license from WFUHS a certain issued U.S.

patent that relates to the use of the TAT-FXN fusion protein for treating FA.

We also in-license from IU United States patents and pending non-provisional applications in the United States and certain foreign countries that relate to the composition of nomlabofusp and methods of use, and certain U.S.

With respect to our patent portfolio, we also in-license from IU United States and E.U.

patents and pending non-provisional applications in the United States and certain foreign countries that relate to the composition of nomlabofusp and methods of use, and certain U.S.

patents relating to materials and methods of use relating to the development of nomlabofusp.

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If we are unable to adequately protect our proprietary technology or maintain issued patents which are sufficient to protect nomlabofusp or potential future product candidates, third parties could compete against us more directly, which would have a material adverse impact on our business, results of operations, financial condition and prospects.

Our key patent relating to nomlabofusp, which we license, will expire in 2040 and we will lose our ability to rely upon this patent to prevent competing products from entering the market, which may impair our ability to generate revenue.

We have in-licensed a certain patent relating to nomlabofusp from WFUHS.

patent relating to use of the TAT-FXN fusion protein for the treatment of FA expires in 2025.

When these patents expire, we will be unable to use these patents to try to block others from marketing nomlabofusp in the United States We have also in-licensed an issued United States patent and pending non-provisional patent applications in the United States and certain foreign countries relating to the composition of nomlabofusp and methods of use from IU.

This United States patent will expire in 2040 at the earliest.

Our key patents relating to nomlabofusp, which we license, will expire in 2040 and we will lose our ability to rely upon these patents to prevent competing products from entering the market, which may impair our ability to generate revenue.

We have in-licensed issued United States and EU patents and pending non-provisional patent applications in the United States and certain foreign countries relating to composition of matter for nomlabofusp and methods of use from IU.

These United States and EU patents will expire in 2040 at the earliest.

Pending applications if issued as patents, would also expire in 2040 at the earliest.

We cannot predict whether these patent applications we and our licensors are currently pursuing will issue as patents in any particular jurisdiction or whether the claims of any issued patents will provide sufficient protection from competitors or other third parties.

When these various patents, if issued, expire, we will be unable to use the patents to try to block others from marketing nomlabofusp in the United States.

We own a certain United States provisional application and certain United States and foreign non-provisional applications and a United States patent relating to our platform technology.

When these various patents, if issued, expire, we will be unable to use the patents to try to block others from marketing nomlabofusp in the United States, EU and certain foreign countries.

We own certain United States and foreign non-provisional applications and a United States patent relating to our platform technology.

The United States Patent will expire in 2041 at the earliest, and the pending applications, if issued as patents, would be expected to expire in 2041.

The provisional application may not be timely converted into a non-provisional application, and we cannot predict whether these provisional applications and non-provisional patent applications will issue as patents in any particular jurisdiction, or whether the claims of any issued patents will provide sufficient protection from competitors or third parties for potential product candidates.

We cannot predict whether these provisional applications and non-provisional patent applications will issue as patents in any particular jurisdiction, or whether the claims of any issued patents will provide sufficient protection from competitors or third parties for potential product candidates.

When these various patents expire, we will be unable to use the patents to try to block others from marketing products pertaining to our platform technology.

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If we were to lose our rights to licensed intellectual property, we may not be able to continue developing or commercializing nomlabofusp, if approved.

We have an exclusive license with WFUHS, pursuant to which we exclusively license certain patent rights relating to use of the TAT-frataxin fusion protein, on a worldwide basis.

We have an exclusive license with IU, pursuant to which we exclusively license certain patent rights relating to nomlabofusp and its use for the treatment of mitochondrial diseases, on a worldwide basis.

Our license agreements with WFUHS and IU impose, and we expect our future license agreements will impose, various development, diligence, commercialization, and other obligations on us in order to maintain the licenses.

In spite of our efforts, WFUHS, IU, or a future licensor might conclude that we have materially breached our obligations under such license agreements and seek to terminate the license agreements, thereby removing or limiting our ability to develop and commercialize products and technology covered by these license agreements.

We have a past license with WFUHS in which we exclusively licensed certain patent rights for patents now expired.

Our license agreement with IU impose, and we expect our future license agreements will impose, various development, diligence, commercialization, and other obligations on us in order to maintain the licenses.

In spite of our efforts, IU, or a future licensor might conclude that we have materially breached our obligations under such license agreement and seek to terminate the license agreement, thereby removing or limiting our ability to develop and commercialize products and technology covered by these license agreements.

If these licenses are terminated, or if the underlying patent rights licensed thereunder fail to provide the intended exclusivity, competitors or other third parties would have the freedom to seek regulatory approval of, and to market, products identical to ours and we may be required to cease our development and commercialization of certain of our product candidates or of nomlabofusp.

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manufacturers.

Our in-licensed patent rights from WFUHS were funded in part by the U.S.

government and are therefore subject to certain federal regulations.

Our previous in-licensed patent rights from WFUHS were funded in part by the U.S.

government and were therefore subject to certain federal regulations.

When new technologies are developed with U.S.

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government funding.

health or safety needs, to meet requirements of federal regulations, or to give preference to U.S.

government may exercise its march-in rights if it determines that action is necessary because we fail to achieve practical application of the government-funded technology, or because action is necessary to alleviate health or safety needs, to meet requirements of federal regulations, or to give preference to

In addition, our rights in such inventions may be subject to certain requirements to manufacture products embodying such inventions in the United States in certain circumstances and if this requirement is not waived.

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• the results of, and delays in, current, and any future, non-clinical or clinical trials of nomlabofusp or any of our future product candidates, including any delays related to a future pandemic, epidemic or outbreak of an infectious disease;

• geopolitical tension, including the potential impact of ongoing conflict between Russia and Ukraine and the current conflict in Israel and Gaza (including any escalation or expansion);

• geopolitical tension, including the potential impact of ongoing conflict of the current conflict in the Middle East (including any further escalation or expansion) and the ongoing conflict between Russia and Ukraine;

• the entry into, or termination of, key agreements, including key licensing or collaboration agreements;

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In the past, following periods of volatility in the market price of a company’s securities, stockholders have often instituted class action securities litigation against those companies.

Such litigation, if instituted, could result in substantial costs and diversion of management’s attention and resources, which could significantly impact our profitability and reputation.

Such litigation, if instituted, could result in substantial costs and diversion of management’s attention and resources, which could significantly impact our

profitability and reputation.

Any lawsuit to which we are a party, with or without merit, may result in an unfavorable judgment.

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Ownership of our common stock is highly concentrated, and it may prevent other stockholders from influencing significant corporate decisions.

Entities affiliated with Deerfield Management Company beneficially own or control approximately 33.3% of our outstanding common stock (assuming no exercise of outstanding options) as of December 31, 2024, on a fully-diluted basis.

Entities affiliated with Deerfield Management Company beneficially own or control approximately 36.8% of our outstanding common stock (assuming no exercise of outstanding options and no conversion of Series A Convertible Preferred Stock) as of December 31, 2025.

Accordingly, such entities have substantial influence over the outcome of a corporate action by us requiring stockholder approval, including the election of directors, any merger, consolidation or sale of all or substantially all of our assets or any other significant corporate transaction.

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These provisions include a classified board of directors, a prohibition on actions by written consent of our stockholders, and the ability of the board of directors to issue preferred stock without stockholder approval.

In addition, because we are in Delaware, we are governed by the provisions of Section 203 of the Delaware General Corporation Law ("DGCL") which prohibits stockholders owning in excess of 15% of our outstanding voting stock from merging or combining with us.

Although we believe these provisions collectively will provide for an opportunity to receive higher bids by requiring potential acquirers to negotiate with our board of directors, they

would apply even if the offer may be considered beneficial by some stockholders.

addition, because we are in Delaware, we are governed by the provisions of Section 203 of the Delaware General Corporation Law (“DGCL”) which prohibits stockholders owning in excess of 15% of our outstanding voting stock from merging or combining with us.

Although we believe these provisions collectively will provide for an opportunity to receive higher bids by requiring potential acquirers to negotiate with our board of directors, they would apply even if the offer may be considered beneficial by some stockholders.

In addition, these provisions may frustrate or prevent any attempts by our stockholders to replace or remove then current management by making it more difficult for stockholders to replace members of the board of directors, which is responsible for appointing the members of management.

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Employee misconduct could also involve the improper use of, including trading on, information obtained in the course of clinical trials, which could result in regulatory sanctions and serious harm to our reputation.

We have adopted a code of conduct, but it is not always possible to identify and deter employee misconduct, and the precautions we take to detect and prevent this activity may be ineffective in controlling unknown or unmanaged risks or losses or in protecting us from governmental investigations or other actions or lawsuits stemming from a failure to comply with these laws or regulations.

unknown or unmanaged risks or losses or in protecting us from governmental investigations or other actions or lawsuits stemming from a failure to comply with these laws or regulations.

In addition, we are subject to the risk that a person or government could allege fraud or other misconduct, even if none occurred.

If any such actions are

instituted against us, and we are not successful in defending ourselves or asserting our rights, those actions could have a significant impact on our business, including the imposition of significant fines or other sanctions.

If any such actions are instituted against us, and we are not successful in defending ourselves or asserting our rights, those actions could have a significant impact on our business, including the imposition of significant fines or other sanctions.

Unfavorable global economic conditions could adversely affect our business, financial condition or results of operations.

Our results of operations could be adversely affected by general conditions in the global economy, geopolitical events and general conditions in the global financial markets.

A severe or prolonged economic downturn due to geopolitical tension resulting from ongoing conflict between Russia and Ukraine and the current conflict in Israel and Gaza (including any escalation or expansion) or other factors could result in a variety of risks to our business, including, weakened demand for our product candidates and our ability to raise additional capital when needed on acceptable terms, if at all.

A severe or prolonged economic downturn due to geopolitical tension resulting from ongoing conflict between Russia and Ukraine and the current conflict in the Middle East (including further escalation or expansion) or other factors could result in a variety of risks to our business, including, weakened demand for our product candidates and our ability to raise additional capital when needed on acceptable terms, if at all.

A weak or declining economy could also strain our suppliers, possibly resulting in supply disruption, or cause our customers to delay making payments for our products.

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Events involving limited liquidity, defaults, non-performance or other adverse developments that affect financial institutions, transactional counterparties or other companies in the financial services industry or the financial services industry generally, or concerns or rumors about any events of these kinds or other similar risks, have in the past and may in the future lead to market-wide liquidity problems.

For example, in early 2023, several financial institutions closed and were taken into receivership by the Federal Deposit Insurance Corporation (“FDIC”).

For example, in early 2023, several financial institutions closed and were taken into receivership by the Federal Deposit Insurance Corporation.

Although we assess our banking and customer relationships as we believe necessary or appropriate, our access to funding sources and other credit arrangements in amounts adequate to finance or capitalize our current and projected future business operations could be significantly impaired by factors that affect us, the financial services industry or economy in general.

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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.

What changed 10-K

Item 1A. Risk Factors