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• maintain, expand and protect our intellectual property portfolio;
−Removed: • hire and retain additional personnel, such as clinical, manufacturing, quality control, regulatory and finance personnel;
+Added: • expand our operational, financial and management systems and hire and retain additional personnel, such as clinical, manufacturing, quality control, regulatory and finance personnel;
• experience any delays or encounter issues with any of the above.
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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.
−Removed: As of December 31, 2023, our existing cash, cash equivalents and marketable securities were $86.8 million, excluding restricted cash of $1.3 million.
−Removed: In February 2024, we completed an underwritten public offering of 19,736,842 shares of our common stock at an offering price of $8.74 per share with net proceeds, after deducting underwriting commissions and offering costs, of approximately $161.6 million.
−Removed: Together with our existing cash, cash equivalents and marketable securities, we have adequate resources to fund our operations into 2026.
+Added: 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.
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.
−Removed: In addition, raising funds in the current economic environment may present substantial challenges, and our expenses will increase as we expand, through development, in-license or acquisition, our pipeline of product candidates.
−Removed: 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.
+Added: 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.
+Added: 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.
+Added: Additionally our expenses will increase as we expand, through development, in-license or acquisition, our pipeline of product candidates.
+Added: 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
+Added: collaborator.
Accordingly, we will need to obtain additional funding in connection with our continuing operations.
−Removed: Our current cash, cash equivalents and marketable securities may not be sufficient to fund all of the
−Removed: efforts that we plan to undertake or to fund the completion of the development and commercialization of nomlabofusp.
+Added: 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.
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.
−Removed: 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, such as COVID-19, or recent liquidity constraints, failures and instability in U.S.
+Added: 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.
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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To the extent we raise additional capital through the sale of equity or convertible debt securities, existing ownership interests will be diluted and the terms of such financings may include liquidation or other preferences that adversely affect the rights of existing stockholders.
−Removed: Debt or equity financings may be coupled with an additional equity component, such as warrants to purchase shares, which could also result in dilution of our existing stockholder’s ownership.
+Added: Debt or equity financings may be coupled with an additional equity component, such as warrants to purchase shares, which could also result in dilution of our existing stockholders' ownership.
If we raise additional funds through strategic partnerships and alliances and licensing arrangements with third parties, we may have to relinquish valuable rights, including future revenue streams, to nomlabofusp or other product candidates that we may develop, in-license or acquire in the future, or grant licenses on terms that are not favorable to us.
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Moreover, NOLs generated in taxable years beginning after December 31, 2017 may be carried forward indefinitely.
−Removed: As of December 31, 2023, the Company had federal net operating loss carryforwards that were generated after December 31, 2017 of $140.3 million that do not expire, however these carryforwards are limited to 80% of the taxable income in any one tax period.
−Removed: 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
−Removed: 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.
+Added: As of December 31, 2024, the Company
+Added: 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.
+Added: 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.
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Risks Related to Our Product Development and Regulatory Approvals
−Removed: The FDA has placed a partial clinical hold on nomlabofusp and there is uncertainty as to when, or if, the FDA will lift the partial clinical hold on our nomlabofusp program, or if it will ever allow further clinical development of nomlabofusp beyond our currently ongoing OLE study at the 25 mg dose level.
−Removed: To support extended dosing of patients with nomlabofusp, we conducted a 26-week NHP toxicology study.
−Removed: In May 2021, we notified the FDA of certain mortalities which occurred at the two highest dose levels in the then ongoing study.
−Removed: On May 25, 2021, the FDA placed a clinical hold on the nomlabofusp clinical program.
−Removed: In the clinical hold letter, the FDA stated that it needed to review a full study report from the then-ongoing NHP study and that we could not initiate additional interventional clinical trials until we submitted such report and received notification from the FDA that additional clinical trials could commence.
−Removed: At the time of the FDA clinical hold, we had no interventional clinical trials with patients enrolling or enrolled.
−Removed: In July 2021, we completed dosing in the 26-week NHP toxicology study.
−Removed: The study included four dose groups in addition to vehicle.
−Removed: Data from the study were collected throughout the second half of 2021 and included in the complete response to the clinical hold submitted to the FDA in January 2022.
−Removed: In February 2022, in response to the complete response to clinical hold, we submitted to the FDA, the FDA stated that it was maintaining the clinical hold and that additional data were needed to resolve the clinical hold.
−Removed: We subsequently submitted a request to the FDA for a Type C meeting, which was granted and held in July 2022.
−Removed: We submitted a complete response to clinical hold incorporating additional information requested by the FDA at the meeting as well as information on the proposed study in August 2022.
−Removed: In September 2022, following the Type C meeting and the submission of the complete response to clinical hold, the FDA allowed the 25 mg cohort of a Phase 2, four-week, placebo-controlled, dose exploration trial of nomlabofusp in FA patients discussed above to proceed.
−Removed: In connection with this decision, the FDA lifted its full clinical hold on the nomlabofusp clinical development program and imposed a partial clinical hold.
−Removed: In June 2023, we met with the FDA.
−Removed: Following that meeting, we submitted a complete response to the FDA’s partial clinical hold that included unblinded safety, PK and frataxin data from the Phase 2 trial’s completed 25 mg cohort.
−Removed: In July 2023, following the FDA’s review of our complete response to the partial clinical hold, the FDA cleared initiation of a second cohort (50 mg) in our four-week, placebo-controlled, Phase 2 dose exploration trial and the initiation of our OLE trial with daily dosing of 25 mg.
−Removed: In January 2024, we initiated the OLE trial evaluating daily subcutaneous injections of 25 mg of nomlabofusp self-administered or administered by a caregiver, with the first patient dosed in March 2024.
−Removed: Dose escalation in the OLE trial will be considered based on safety, tolerability, PK, and tissue FXN levels from the Phase 2 trial’s 50 mg cohort as well as available data from the 25 mg dose of nomlabofusp in the OLE trial, and is contingent on FDA review as part of the partial clinical hold.
−Removed: Initial data from the OLE trial is expected in the fourth quarter of 2024.
−Removed: In February 2024, we reported positive top-line data and successful completion of both the 25 mg cohort and the 50 mg cohort of our four-week, placebo-controlled Phase 2 dose exploration study of nomlabofusp in participants with FA.
−Removed: Nomlabofusp was generally well tolerated and demonstrated dose dependent increases in FXN levels in all evaluated tissues (skin and buccal cells) after daily dosing of 14 days followed by every other day dosing until day 28 in the 25 mg and 50 mg cohorts.
−Removed: Our business may be adversely affected if the FDA partial clinical hold does not enable the development program to proceed as planned, if the FDA places a full clinical hold on the development of nomlabofusp, or, if additional non-clinical or clinical studies are required.
−Removed: This may cause significant delays or expense in developing nomlabofusp.
Our success is currently dependent upon the success of our lead product candidate, nomlabofusp.
−Removed: We cannot be certain that data from both cohorts of our Phase 2 dose exploration study augmented by data from the OLE trial will provide the FDA with adequate data to remove the partial clinical hold on nomlabofusp, allow the nomlabofusp development program to proceed as planned in part or in full, or that we will ultimately be successful with our clinical development or that we will be ever able to obtain regulatory approval for nomlabofusp.
−Removed: 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 in patients with FA.
−Removed: In January 2024, as permitted by the FDA, we initiated the OLE trial evaluating daily subcutaneous injections of 25 mg of nomlabofusp self-administered or administered by a caregiver, with the first patient dosed in March 2024.
−Removed: Participants who completed treatment in the Phase 2 dose exploration trial, or who previously completed a prior clinical trial of nomlabofusp are potentially eligible for the OLE.
−Removed: Dose escalation in the OLE trial will be considered based on safety, PK, and tissue FXN levels from the 25 mg dose of nomlabofusp in the OLE trial, as well as other data from the Phase 2 trial’s 50 mg cohort, and is contingent on FDA review as part of the partial clinical hold.
−Removed: We cannot provide any assurance that the data from our Phase 1 and Phase 2 trials augmented by data from the OLE trial will prove the FDA with adequate data to remove the partial clinical hold, allow us to continue our development of nomlabofusp, or that we will ultimately be successful in our clinical development.
+Added: 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.
+Added: 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.
+Added: 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.
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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.
+Added: 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.
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:
−Removed: • maintaining our IND with the FDA in order to continue to conduct clinical trials in the United States, including our ability to expand to higher doses or have the partial clinical hold lifted by the FDA on a timely basis, if at all;
+Added: • 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;
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• establishing and maintaining arrangements with third-party manufacturers for nomlabofusp, including developing, validating and maintaining a commercially viable manufacturing process that is compliant with cGMPs;
+Added: • developing, validating and implementing a potency control strategy acceptable to the FDA, EMA and other comparable regulatory authorities;
• maintaining and growing an organization of scientists and business people who can develop our product candidates and technology;
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The historical failure rate for product candidates in our industry is high, especially for products in early stages of development.
−Removed: The results from non-clinical studies, toxicology studies or clinical trials of a product candidate may not predict the results of later non-clinical or clinical trials of the product candidate, or in clinical trials with different patient populations such as children and adolescents and interim results of a clinical trial are not necessarily
−Removed: indicative of final results.
+Added: The results from non-clinical studies, toxicology studies or clinical trials of a product candidate may not predict the results of later non-clinical or clinical trials of the product candidate, or in clinical trials with different patient populations such as children and adolescents and interim results of a clinical trial are not necessarily indicative of final results.
Product candidates in later stages of clinical trials may fail to show the desired safety and efficacy characteristics despite having progressed through non-clinical studies and initial clinical trials.
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• lack of adequate funding to continue the clinical trial;
−Removed: • challenges in recruiting and enrolling patients to participate in clinical trials, including the size and nature of the patient population, such as pediatric patients, the proximity of patients to clinical trial sites, eligibility criteria for the clinical trial, the nature of the clinical trial protocol, the availability of approved effective treatments for the relevant disease and competition from FDA-approved therapeutics for FA, other clinical trial programs for similar indications, and the resurgence of vaccine resistant, more deadly or more contagious variants of COVID-19 and the efforts to mitigate those effects;
+Added: • challenges in recruiting and enrolling patients to participate in clinical trials, including the size and nature of the patient population, such as pediatric patients, the proximity of patients to clinical trial sites, eligibility criteria for the clinical trial, the nature of the clinical trial protocol, the availability of approved effective treatments for the relevant disease and competition from FDA-approved therapeutics for FA and other clinical trial programs for similar indications;
• difficulties in retaining or recruiting clinical investigators in our ongoing or future clinical trials;
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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.
−Removed: 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 of nomlabofusp in FA patients.
−Removed: The FDA has agreed that we may commence our OLE study in patients who previously participated in one of our previous nomlabofusp clinical trials at the 25 mg level.
−Removed: We cannot be certain that data from both cohorts of our Phase 2 dose exploration study augmented by data from the OLE study will provide the FDA with adequate data to remove the current partial clinical hold on nomlabofusp.
−Removed: Clinical trials may also 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.
+Added: 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.
+Added: We have an ongoing Phase 2 OLE trial in patients with FA and an ongoing run-in study in adolescent patients with FA.
+Added: 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.
If future clinical trials of nomlabofusp fail or further delays occur in the United States and or other countries, we may not be able to develop and commercialize nomlabofusp and could fail to realize the potential advantages of doing so, and it could materially adversely affect our business, financial condition and results of operations.
−Removed: In addition, disruptions caused by future pandemic, epidemic or outbreak of an infectious disease, such as the COVID-19 pandemic may increase the likelihood that we encounter such difficulties or delays in initiating, enrolling, conducting or completing our planned and ongoing clinical trials.
−Removed: Further, FA is a rare disease, 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.
−Removed: In addition, given the limited number of FA patients, the recent 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.
+Added: 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.
+Added: 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.
+Added: 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.
Any inability to successfully initiate or complete clinical trials could result in additional costs to us or impair our ability to generate revenue from product sales.
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We have little experience in later stage clinical development, and related regulatory requirements or the commercialization of products.
−Removed: As a result, we have not yet demonstrated our ability to independently and repeatedly conduct clinical development after Phase 1, successfully conduct an international multi-center clinical trial, conduct a pivotal clinical trial, obtain regulatory approval, manufacture drug product on a commercial scale or
−Removed: arrange for a third party to do so on our behalf, and commercialize therapeutic products.
−Removed: 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.
+Added: As a result, we have not yet demonstrated our ability to independently and repeatedly conduct clinical development after Phase 1, 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.
+Added: We will need to develop such abilities if we are to execute on our business strategy to develop and independently commercialize product
+Added: candidates for orphan and niche indications.
To execute on our business plan for the development of independent programs, we will need to successfully:
−Removed: • obtain the FDA's permission to continue with the clinical development of nomlabofusp beyond our currently ongoing OLE study at the 25 mg dose level;
• execute our clinical development plans for product candidates;
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We completed two Phase 1 and our four-week, placebo-controlled Phase 2 dose exploration study.
−Removed: As a result of certain mortalities in a non-clinical study of NHPs, the FDA issued a clinical hold in May 2021.
−Removed: In September 2022, following a Type C meeting and the submission of our complete response to the partial clinical hold, the FDA allowed the 25 mg cohort of a Phase 2, four-week, placebo-controlled, dose exploration trial of nomlabofusp in FA patients to proceed.
−Removed: In connection with this decision, the FDA lifted its full clinical hold on the nomlabofusp clinical development program and imposed a partial hold.
−Removed: In June 2023, we met with the FDA.
−Removed: Following that meeting, we submitted a complete response to the FDA’s partial clinical hold that included unblinded safety, PK and frataxin data from the Phase 2 trial’s completed 25 mg cohort.
−Removed: In July 2023, following the FDA’s review of our complete response to the partial clinical hold, the FDA cleared initiation of a second cohort at 50 mg of our four-week, placebo-controlled, Phase 2 dose exploration trial and to initiate our OLE trial with daily dosing of 25 mg.
−Removed: In February 2024, we reported positive top-line data and successful completion of our four-week, placebo-controlled Phase 2 dose exploration study of nomlabofusp in participants with FA.
−Removed: Nomlabofusp was generally well tolerated and demonstrated dose dependent increases in FXN levels in all evaluated tissues (skin and buccal cells) after daily dosing of 14 days followed by every other day dosing until day 28 in the 25 mg and 50 mg cohorts.
−Removed: Participants in the 25 mg (n=13) and 50 mg (n=15) cohorts were randomized 2:1 to receive subcutaneous injections of nomlabofusp or placebo.
−Removed: The initiation of additional U.S.
−Removed: clinical trials evaluating nomlabofusp are contingent on FDA review of data under the partial clinical hold.
−Removed: The FDA has agreed that we may commence our OLE study in patients who previously participated in one of our previous nomlabofusp clinical trials at the 25 mg level dosed daily.
−Removed: We cannot be certain that data from both cohorts of our Phase 2 dose exploration study augmented by data from the OLE study will provide the FDA with adequate data to remove the current partial clinical hold on nomlabofusp, allow the nomlabofusp development program to proceed as planned in part or in full, or that we will ultimately be successful with our clinical development or that we will be ever able to obtain regulatory approval for.
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.
Adverse toxicology or safety results could lead to clinical holds or other developmental delays.
−Removed: Interim results of clinical
−Removed: trials do not necessarily predict success in those or future clinical trials.
+Added: Interim results of clinical trials do not necessarily predict success in those or future clinical trials.
Success in adult clinical trials may not predict the outcome of pediatric clinical trials.
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In addition, FDA, EMA or foreign regulatory authorities may disagree with the extent of population exposure to assess clinical safety.
−Removed: 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.
+Added: 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
+Added: an application for approval by the FDA, EMA or another regulatory authority.
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.
+Added: The FDA and other comparable foreign authorities have substantial discretion in the approval process and determining when or whether regulatory approval will be granted for any product candidate that we develop and may decide that our data are insufficient for approval or require additional non-clinical, clinical, or other data.
+Added: 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.
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There are currently no FDA-approved products to treat FA that are designed to increase frataxin levels.
−Removed: 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.
+Added: 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
+Added: 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.
−Removed: Recently, we had discussions with the FDA regarding the use of tissue FXN levels as a novel surrogate endpoint.
−Removed: The FDA has 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.
−Removed: We intend to pursue an accelerated approval using FXN levels, supportive PD and clinical information, and safety data from the OLE study, along with additional non-clinical pharmacology information needed to support the novel surrogate endpoint approach.
−Removed: We are beginning to plan for a confirmatory study and are targeting a BLA submission in the second half of 2025.
+Added: We have had discussions with the FDA regarding the use of tissue FXN levels as a novel surrogate endpoint.
+Added: 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.
+Added: 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.
+Added: 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.
+Added: 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.
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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.
−Removed: Any adverse events or undesirable side effects caused by, or other unexpected properties of, nomlabofusp in non-clinical or clinical studies could cause us, any future collaborators, an IRB or ethics committee or regulatory authorities to interrupt, delay or halt clinical trials of our product candidate and could result in a more restrictive
−Removed: label or the delay or denial of regulatory approval by the FDA or other regulatory authorities.
−Removed: Should the FDA permit us to continue with the clinical development of nomlabofusp, 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.
−Removed: If such side effects become known later in development or after approval, such findings may harm our business, financial condition and prospects significantly.
+Added: Any adverse events or undesirable side effects caused by, or other unexpected properties of, nomlabofusp in non-clinical or clinical studies could cause us, any future collaborators, an IRB or ethics committee or regulatory authorities to interrupt, delay or halt clinical trials of our product candidate and could result in a more restrictive label or the delay or denial of regulatory approval by the FDA or other regulatory authorities.
+Added: 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.
+Added: For example, recently our Safety Monitoring Team deemed anaphylaxis as an adverse drug reaction likely associated with nomlabofusp.
+Added: To reduce the risk of allergic reactions, including anaphylaxis, we amended the OLE protocol to administer premedication for the first month of dosing.
+Added: 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.
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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.
−Removed: 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.
+Added: Production difficulties caused by unforeseen events may delay the availability of material for clinical trials and commercial products for nomlabofusp or any
+Added: 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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Designation for these programs is within the discretion of the FDA.
−Removed: Accordingly, even if we believe nomlabofusp or a future product candidate meets the criteria for designation, the
−Removed: FDA may disagree.
+Added: Accordingly, even if we believe nomlabofusp or a future product candidate meets the criteria for designation, the FDA may disagree.
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.
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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.
−Removed: We intend to pursue an accelerated approval from FDA for nomlabofusp for the treatment of FA using FXN levels, supportive pharmacodynamic and clinical information and safety data from the OLE study, along with additional non-clinical pharmacology information needed to support our surrogate biomarker approach.
+Added: 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
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.
−Removed: Although we have initiated discussions with FDA concerning our surrogate biomarker approach, there can be no assurance that data we intend to generate will be successful in establishing that increases in FXN levels are reasonably likely to predict clinical benefit.
−Removed: In addition, future nonclinical 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.
+Added: 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.
+Added: 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.
+Added: 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.
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Changes to or termination of the accelerated approval program could prevent or limit our ability to obtain accelerated approval of any of our clinical development programs.
−Removed: Recently, the accelerated
−Removed: approval pathway has come under scrutiny within the FDA and by Congress.
+Added: Recently, the accelerated approval pathway has come under scrutiny within the FDA and by Congress.
The FDA has put increased focus on ensuring that confirmatory studies are conducted with diligence and, ultimately, that such studies confirm the benefit.
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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.
−Removed: 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 indication for seven years, except in limited circumstances, including if the FDA concludes that the later drug is clinically superior to the approved drug.
+Added: 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
+Added: 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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Moreover, orphan drug exclusivity may not effectively protect our product candidates from competition because different drugs can be approved for the same condition.
−Removed: Further, even after an orphan drug is approved, the FDA or comparable foreign regulatory authority can subsequently approve another drug for the same condition if such regulatory authority concludes that the later drug is clinically superior, if it is shown to be safer, more effective or makes a major contribution to patient care.
−Removed: We have also received orphan drug designation for nomlabofusp in the European Union.
−Removed: In the European Union, the European Medicines Agency, or EMA’s Committee for Orphan Medicinal Products grants orphan drug designation to promote the development of products that are intended for the diagnosis, prevention or treatment of life threatening or chronically debilitating conditions affecting not more than five in 10,000 persons in the European Union.
+Added: Further, even after an orphan drug is approved, the FDA or comparable foreign regulatory authority can subsequently approve another drug for the same condition if such regulatory authority concludes that the later drug is clinically superior, which means that it is shown to be safer, more effective or makes a major contribution to patient care.
+Added: We have also received orphan designation for nomlabofusp in the European Union.
+Added: 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.
−Removed: 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 drug approval.
+Added: 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.
+Added: 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.
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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.
−Removed: The rare pediatric disease priority review voucher program was most recently reauthorized by Congress through September 30, 2024, with the potential for priority review vouchers to be granted through September 30, 2026.
+Added: 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.
+Added: 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.
+Added: After September 30, 2026, the FDA may not award any rare pediatric disease priority review vouchers.
+Added: Congress may vote to reauthorize this program, but its future remains unknown at this time.
We received rare pediatric disease designation from the FDA for nomlabofusp in 2019.
−Removed: We may, in the future, apply for rare pediatric disease designation from the FDA for future product candidates that may qualify for designation.
+Added: 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.
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nomlabofusp may receive approval in adults, but not pediatric patients;
−Removed: nomlabofusp may not meet the eligibility requirements for a priority voucher at the time we seek approval for nomlabofusp;
+Added: nomlabofusp may not meet the eligibility requirements for a priority voucher at
+Added: 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.
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.
−Removed: If we apply for designation for future product candidates as drugs for rare pediatric diseases, the FDA may not grant the designation.
+Added: 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.
The failure to maintain rare pediatric disease designation for nomlabofusp or if FDA approval does not occur prior to September 30, 2026 could result in the inability to receive a priority review voucher which could adversely affect our business, financial condition and results of operations.
−Removed: If we fail to maintain PRIME designation in the European Union for nomlabofusp, our competitive position would be harmed.
−Removed: The PRIME scheme is open to medicines under development and for which the applicant intends to apply for an initial MAA through the centralized procedure.
−Removed: 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) and they must demonstrate the potential to address the unmet medical need by introducing new methods or therapy or improving existing ones.
+Added: If we fail to maintain PRIME designation in the European Union for nomlabofusp, our competitive position could be harmed.
+Added: The PRIME scheme is open to medicines under development and for which the applicant intends to apply for an MA through the centralized procedure.
+Added: 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.
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.
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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.
−Removed: Approval of other therapies for the treatment Friedreich’s ataxia, including the recent approval of omaveloxolone could negatively impact our continued access to this and similar programs.
−Removed: Loss of PRIME designation for nomlabofusp or
−Removed: the failure to obtain such designation for any future product candidates could adversely affect our business, financial condition and results of operation.
+Added: 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.
+Added: 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.
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.
−Removed: 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.
+Added: If we experience delays completing, or if we terminate, any of our clinical trials, or if
+Added: 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.
−Removed: Disruptions at the FDA and other government agencies caused by funding shortages or global health concerns could hinder their ability to hire, retain or deploy 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, which could negatively impact our business.
−Removed: The ability of the FDA to review and/or approve new products can be affected by a variety of factors, including government budget and funding levels, statutory, regulatory, and policy changes, the FDA’s ability to hire and retain key personnel, and accept the payment of user fees, and other events that may otherwise affect the FDA’s ability to perform routine functions.
−Removed: In addition, government funding of other government agencies that fund research and development activities is subject to the political process, which is inherently fluid and unpredictable.
−Removed: Disruptions at the FDA and other agencies may also slow the time necessary for new drugs to be reviewed and/or approved by necessary government agencies, which would adversely affect our business.
−Removed: Furthermore, government shutdowns could also impact the ability of regulatory authorities and government agencies to function normally and support our operations.
−Removed: For example, the U.S.
−Removed: federal government has shut down repeatedly since 1980, including for a period of 35 days beginning on December 22, 2018.
−Removed: During a shutdown, certain regulatory authorities and agencies, such as the FDA, have had to furlough key personnel and stop critical activities.
−Removed: If a prolonged government shutdown occurs, or if global health concerns prevent the FDA or other regulatory authorities from conducting their regular inspections, reviews, or other regulatory activities, 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.
+Added: 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.
+Added: The current administration is focused on reducing costs of the federal government generally, including significantly reducing the number of government employees.
+Added: Without appropriation of additional funding to federal agencies, our business operations related to our product development activities for the U.S.
+Added: market could be impacted.
+Added: The ability of the FDA or comparable foreign regulatory authorities to review and approve new products can be affected by a variety of factors, including government budget and funding levels, ability to hire and retain key personnel, and accept the payment of user fees, statutory, regulatory and policy changes.
+Added: In addition, government funding of other government agencies or comparable foreign regulatory authorities on which our operations may rely, including those that fund research and development activities is subject to the political process, which is inherently fluid and unpredictable.
+Added: Disruptions at the FDA, other agencies or comparable foreign regulatory authorities may also slow the time necessary for new drugs to be reviewed and/or approved by necessary government agencies, which would adversely affect our business.
+Added: Changes in FDA staffing could result in delays in the FDA’s responsiveness or in its ability to review submissions or applications, issue regulations or guidance, or implement or enforce regulatory requirements in a timely fashion or at all.
+Added: Similar consequences would also result in the event of another significant shutdown of the federal government.
+Added: As an example, over the last several years, the U.S.
+Added: 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.
+Added: 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.
+Added: Further, government shutdowns could impact our ability to access the public markets and obtain additional capital in the future.
Regulatory requirements governing biologic products have changed frequently and may continue to change in the future.
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As a result, it is difficult to determine how long it will take or how much it will cost to obtain regulatory approvals for nomlabofusp for the treatment of FA or any other future protein replacement therapy product candidates in any indication, if at all.
−Removed: Regulatory review agencies and the new requirements and guidelines they promulgate may lengthen the regulatory review process, require us to perform additional or larger studies, increase
−Removed: our development costs, lead to changes in regulatory positions and interpretations, delay or prevent approval and commercialization of our product candidates or lead to significant post-approval studies, limitations or restrictions.
+Added: Regulatory review agencies and the new requirements and guidelines they promulgate may lengthen the regulatory review process, require us to perform additional or larger studies, increase our development costs, lead to changes in regulatory positions and interpretations, delay or prevent approval and commercialization of our product candidates or lead to significant post-approval studies, limitations or restrictions.
Legislative and regulatory proposals have been made to expand post-approval requirements and restrict sales and promotional activities for pharmaceutical products.
−Removed: 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.
+Added: 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
+Added: 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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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.
−Removed: 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 a MAA from the EMA, or in any other foreign countries until we receive the requisite marketing approval from such countries.
+Added: 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.
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It is possible that governmental authorities will conclude that our business practices do not comply with current or future statutes, regulations or case law involving applicable fraud and abuse or other healthcare laws and regulations.
−Removed: If our operations, 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
−Removed: 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.
−Removed: 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.
+Added: 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.
+Added: 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
+Added: 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.
−Removed: Healthcare reform initiatives recently culminated in the enactment of the IRA Inflation Reduction Act of 2022 or 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.
−Removed: For more information, see the section of this report titled “Business – Healthcare Laws and Regulations – Healthcare Reform.”
+Added: 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.
+Added: 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.
+Added: The law establishes a private right of action allowing developers to sue application holders that refuse to sell them product samples needed to support their applications.
+Added: If we are required to provide product samples or allocate additional resources to respond to such requests or any legal challenges under this law, our business could be adversely impacted.
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.
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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.
−Removed: To obtain 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
−Removed: with other available therapies.
+Added: 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.
If reimbursement for product candidates that we elect to sell on our own is unavailable in any country in which we seek reimbursement, if it is limited in scope or amount, if it is conditioned upon our completion of additional clinical trials, or if pricing is set at unsatisfactory levels, our business, financial conditions and results of operations could be materially adversely affected.
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Mergers and acquisitions in the pharmaceutical and biotechnology industries may result in even more resources being concentrated among a smaller number of our competitors.
−Removed: Smaller or early-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established
+Added: Smaller or early-stage companies may
+Added: 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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Our products may also experience greater competition from lower cost biosimilars or generics that come to market when branded products that compete with our products lose their own patent protection.
−Removed: In the European Union, the European Commission has granted marketing authorizations for biosimilars pursuant to a set of general and product class-specific guidelines for biosimilar approvals issued in 2005.
+Added: In the European Union, the European Commission has granted marketing authorizations for biosimilars pursuant to a set of general and product class-specific guidelines for biosimilar approvals originally issued in 2005 and updated in 2014.
In addition, in an effort to spur biosimilar utilization and/or increase potential healthcare savings, some countries in the European Union have adopted biosimilar uptake measures such as requiring physician prescribing quotas or promoting switching or pharmacy substitution of biosimilars for the corresponding reference products, and other countries may adopt similar measures.
Some countries in the European Union may impose automatic price reductions upon market entry of the second or third biosimilar competitor.
−Removed: In the United States, the ACA authorized the FDA to approve biosimilars via a separate, abbreviated pathway.
+Added: In the United States, the ACA authorized the FDA to license biosimilars via a separate, abbreviated pathway.
A growing number of companies have announced that they are in varying stages of development of biosimilar versions of existing biotechnology products.
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pathway includes the option for biosimilar products meeting certain criteria to be approved as interchangeable with their reference products.
−Removed: Some companies developing biosimilars may seek to register their products as interchangeable biologics, which could make it easier for prescribers or pharmacists to substitute those biosimilars for our products.
−Removed: In addition, critics of the 12-year exclusivity period in the biosimilar pathway law will likely continue to seek to shorten the data exclusivity period and/or to encourage the FDA to interpret narrowly the law’s provisions regarding which new products receive data exclusivity.
+Added: Some companies developing biosimilars may seek to license their products as interchangeable biologics, which could make it easier for prescribers or pharmacists to substitute those biosimilars for our products.
+Added: In addition, critics of the 12-year exclusivity period in the biosimilar pathway will likely continue to seek to shorten the data exclusivity period and/or to encourage the FDA to interpret narrowly the law’s provisions regarding which new products receive data exclusivity.
While we are unable to predict the precise impact of biosimilars, we expect in the future for there to be greater competition in the United States as a result of biosimilars and downward pressure on product prices and sales.
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Whether we reach a definitive agreement for a collaboration for nomlabofusp or other potential product candidates will depend, among other things, upon our assessment of the collaborator’s resources and expertise, the terms and conditions of the proposed collaboration and the proposed collaborator’s evaluation of a number of factors.
−Removed: 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
−Removed: 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.
−Removed: 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.
+Added: 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.
+Added: The collaborator may also
+Added: 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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We face risks related to health epidemics, and/or other outbreaks of communicable diseases, which could significantly disrupt our operations and may materially and adversely affect our business and financial conditions.
−Removed: Our business could be adversely impacted by the effects of a global pandemic, epidemic or outbreak of an infectious disease, such as, for example, a possible resurgence of vaccine resistant or more highly contagious or deadly variants of COVID-19 and the efforts to mitigate such outbreaks.
+Added: Our business could be adversely impacted by the effects of a global pandemic, epidemic or outbreak of an infectious disease.
Such global outbreaks of communicable diseases globally could materially and adversely impact our operations, including without limitation, our manufacturing and supply chain for nomlabofusp and our planned clinical trials, which could continue to face, enrollment difficulties as hospitals or clinical trials sites experience closures.
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and other adverse business consequences.
−Removed: 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).
+Added: 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,
+Added: 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.
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13,709/2018), and China’s Personal Information Protection Law (PIPL) impose strict requirements for processing personal data.
−Removed: For example, under the GDPR, companies may face temporary or definitive bans on data processing and other corrective actions;
+Added: 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;
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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Europe and other jurisdictions have enacted laws requiring data to be localized or limiting the transfer of personal data to other countries.
−Removed: In particular, the European Economic Area (EEA) and the UK have significantly restricted the transfer of personal data to the United States and other countries whose privacy laws it believes are inadequate.
+Added: 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.
Other jurisdictions may adopt similarly stringent interpretations of their data localization and cross-border data transfer laws.
−Removed: Although 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 standard contractual clauses, the UK’s International Data Transfer Agreement / Addendum, and the EU-U.S.
−Removed: Data Privacy Framework and the UK extension thereto (which allows for transfers to relevant U.S.-based organizations who self-certify compliance and
−Removed: participate in the Framework), these mechanisms are subject to legal challenges, and there is no assurance that we can satisfy or rely on these measures to lawfully transfer personal data to the United States.
−Removed: If there is no lawful manner for us 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.
−Removed: Some European regulators have ordered certain companies to suspend or permanently cease certain transfers of personal data to recipients outside Europe for allegedly violating the GDPR’s cross-border data transfer limitations.
−Removed: Additionally, companies that transfer personal data to recipients outside of the EEA and/or UK to other jurisdictions, particularly to the United States, are subject to increased scrutiny from regulators individual litigants and activist groups.
+Added: 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
+Added: 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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We may at times fail (or be perceived to have failed) in our efforts to comply with our data privacy and security obligations.
−Removed: Moreover, despite our efforts, our personnel or third parties on whom we rely on may fail to comply with such obligations, which could negatively impact our business operations.
+Added: Moreover, despite our efforts, our personnel or third parties on whom we rely may fail to comply with such obligations, which could negatively impact our business operations.
If we or the third parties on which we rely fail, or are perceived to have failed, to address or comply with applicable data privacy and security obligations, we could face significant consequences, including but not limited to:
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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.
−Removed: 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,
−Removed: unauthorized access, natural disasters, terrorism, war, and telecommunication and electrical failures.
+Added: 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.
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.
−Removed: 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.
+Added: 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
+Added: 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.
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These threats come from a variety of sources, including traditional computer “hackers,” hacktivists, threat actors, personnel misconduct or error (such as through theft or misuse), organized criminal threat actors, sophisticated nation-states, and nation-state-supported actors.
−Removed: Some actors now engage and are expected to continue to engage in cyber-attacks, including without limitation nation-state actors for geopolitical reasons and in
−Removed: conjunction with military conflicts and defense activities.
+Added: Some actors now engage and are expected to continue to engage in cyber-attacks, including without limitation nation-state actors for geopolitical reasons and in conjunction with military conflicts and defense activities.
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.
−Removed: 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 AI, telecommunications failures, earthquakes, fire, flood, and other similar threats.
+Added: 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,
+Added: 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.
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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The successful assertion of one or more large claims against us that exceeds our available insurance coverage, or results in changes to our insurance policies (including premium increases or the imposition of large deductible or co-insurance requirements), could have an adverse effect on our business.
+Added: We face risks related to information technology regulatory and compliance requirements
+Added: We are subject to an evolving landscape of data privacy and security regulations, including the General Data Protection Regulation (GDPR), Health Insurance Portability and Accountability Act (HIPAA), California Consumer Privacy Act (CCPA), SEC cybersecurity disclosure requirements, among others.
+Added: Failure to comply with these regulations may result in substantial fines, litigation, regulatory investigations, and reputational harm.
+Added: The complexity of maintaining compliance across multiple jurisdictions increases our operational burden, requiring continuous updates to security policies, employee training, and IT infrastructure enhancements.
+Added: Additionally, new or amended privacy laws may impose additional costs and operational challenges, impacting our ability to conduct business effectively.
+Added: If we or one of our third-party service providers fail to adhere to regulatory requirements, we may be subject to enforcement actions, consent decrees, or restrictions on our ability to process sensitive data, potentially delaying our product development or commercialization efforts.
+Added: Many of our critical IT systems and data storage rely on cloud service providers.
+Added: While these providers implement security controls, misconfigurations, lack of visibility into shared responsibility models, or insider threats can lead to data exposure or service disruptions.
+Added: Failure to comply with evolving global data privacy and security regulations, such as GDPR, HIPAA, CCPA, SEC cybersecurity rules, and industry-specific compliance requirements (e.g., FDA 21 CFR Part 11 for regulated data), could subject us to significant fines, legal liabilities, and reputational harm.
+Added: We face the risk of shadow IT and unapproved software use by employees
+Added: 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".
+Added: The use of such unapproved technologies increases security risks, as these applications and services may not adhere to our established cybersecurity and compliance standards.
+Added: 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.
+Added: Additionally, unvetted third-party applications may not comply with regulatory requirements, exposing us to compliance violations and potential legal liabilities.
+Added: Despite our ongoing efforts to monitor and control the use of unauthorized software, we may not be able to eliminate all instances of Shadow IT, which could materially impact our security posture, regulatory compliance, and business operations.
We face potential product liability exposure, and, if claims are brought against us, we may incur substantial liability.
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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.
−Removed: 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.
+Added: Any such product liability claims
+Added: 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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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.
−Removed: Regulatory authorities ensure compliance with these requirements through periodic inspections of trial sponsors, principal investigators and clinical trial sites.
+Added: Regulatory authorities ensure compliance with these requirements through periodic inspections of trial sponsors, principal investigators and
+Added: 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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Our CROs and contractors are not our employees, and except for remedies available to us under our agreements with such CROs and contractors, we cannot control whether or not they devote sufficient time and resources to our ongoing clinical and non-clinical programs.
−Removed: If our CROs and contractors do not successfully carry out their contractual duties or obligations or meet expected deadlines or if the quality or accuracy of the clinical data they obtain is compromised due to the failure to adhere to our clinical protocols, regulatory requirements or for other
−Removed: reasons, our clinical trials may be extended, delayed or terminated and we may not be able to obtain regulatory approval for or successfully commercialize our product candidates.
+Added: If our CROs and contractors do not successfully carry out their contractual duties or obligations or meet expected deadlines or if the quality or accuracy of the clinical data they obtain is compromised due to the failure to adhere to our clinical protocols, regulatory requirements or for other reasons, our clinical trials may be extended, delayed or terminated and we may not be able to obtain regulatory approval for or successfully commercialize our product candidates.
As a result, our operations and the commercial prospects for our product candidates would be harmed, our costs could increase and our ability to generate revenue could be delayed or reduced.
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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.
−Removed: In particular, replacement of any product formulation manufacturer we may engage could require significant effort and expertise
−Removed: because there may be a limited number of qualified replacements.
+Added: 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.
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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.
−Removed: 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:
+Added: Our or a third party’s failure to execute on our
+Added: 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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Our commercial success will depend in part on our success in obtaining and maintaining issued patents and other intellectual property rights in the United States and elsewhere and protecting our proprietary technology.
−Removed: If we do not adequately protect our intellectual property and proprietary technology, competitors may be able to use our
−Removed: technologies and erode or negate any competitive advantage we may have, which could harm our business and ability to achieve profitability.
−Removed: With respect to our patent portfolio, we in-license from WFUHS certain issued U.S.
−Removed: patents that relate to nomlabofusp and its use for treating FA.
−Removed: We also in-license from IU a United States patent 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.
+Added: 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.
+Added: With respect to our patent portfolio, we in-license from WFUHS a certain issued U.S.
+Added: patent that relates to the use of the TAT-FXN fusion protein for treating FA.
+Added: 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.
patents relating to materials and methods of use relating to the development of nomlabofusp.
−Removed: We also own or co-own pending international PCT, foreign and United States non-provisional applications, a United States Patent, and United States provisional applications relating to the development of nomlabofusp, including methods of use of nomlabofusp, biomarkers and to our peptide delivery platform technology.
+Added: We also own or co-own pending international PCT, foreign and United States non-provisional applications, United States Patents, and United States provisional applications relating to the development of nomlabofusp, including methods of use of nomlabofusp, biomarkers and to our peptide delivery platform technology.
In some cases, we have only filed provisional patent applications on certain aspects of our technologies and each of these provisional patent applications is not eligible to become an issued patent until, among other things, we file a non-provisional patent application within 12 months of the filing date of the applicable provisional patent application.
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Such proceedings could also provoke third parties to assert claims against us, including that some or all of the claims in one or more of our patents are invalid or otherwise unenforceable.
−Removed: If any of our patents covering nomlabofusp are invalidated or found unenforceable, our financial
−Removed: position and results of operations would be materially and adversely impacted.
+Added: If any of our patents covering nomlabofusp are invalidated or found unenforceable, our financial position and results of operations would be materially and adversely impacted.
In addition, if a court found that valid, enforceable patents held by third parties covered nomlabofusp, our financial position and results of operations would also be materially and adversely impacted.
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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.
−Removed: Our key patent, which we license relates to nomlabofusp 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.
−Removed: We have in-licensed certain patents relating to nomlabofusp from WFUHS.
−Removed: patents relating to nomlabofusp and its use for the treatment of FA expire in 2024 and 2025, respectively.
+Added: 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.
+Added: We have in-licensed a certain patent relating to nomlabofusp from WFUHS.
+Added: 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.
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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 2041-2044.
−Removed: The provisional application may not be timely converted into a non-provisional application, and we cannot predict
−Removed: 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.
+Added: 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.
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 are unable to avoid infringing the patent rights of others, we may be required to seek a license, defend an infringement action or challenge the validity of the patents in court, or redesign our products.
−Removed: Patent litigation is costly and time consuming.
+Added: Patent litigation is costly and time
We may not have sufficient resources to bring these actions to a successful conclusion.
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PTO, or made a misleading statement, during prosecution.
−Removed: Third parties may also raise similar claims before administrative bodies in the United States or abroad, even outside the context of
+Added: Third parties may also raise similar claims before administrative bodies in the United States or abroad, even outside the context of litigation.
Such mechanisms include re-examination, post grant review and equivalent proceedings in foreign jurisdictions, e.g.
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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.
−Removed: We have an exclusive license with WFUHS, pursuant to which we exclusively license certain patent rights relating to the TAT-frataxin fusion protein and its use, on a worldwide basis.
+Added: 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.
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manufacturers.
−Removed: Our in-licensed patent rights from WFUHS and IU were funded in part by the U.S.
+Added: Our in-licensed patent rights from WFUHS were funded in part by the U.S.
government and are therefore subject to certain federal regulations.
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government funding.
−Removed: 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 U.S.
+Added: 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
+Added: health or safety needs, to meet requirements of federal regulations, or to give preference to U.S.
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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We have not yet registered trademarks for a commercial trade name for nomlabofusp or other potential product candidates and failure to secure such registrations could adversely affect our business, financial condition and results of operations.
−Removed: We have not yet registered trademarks for a commercial trade name for nomlabofusp or other potential product candidates.
+Added: In many jurisdictions, we have not yet registered trademarks for a commercial trade name for nomlabofusp or other potential product candidates.
Any future trademark applications may be rejected during trademark registration proceedings.
Although we would be given an opportunity to respond to those rejections, we may be unable to overcome such rejections.
−Removed: In addition, the U.S.
−Removed: PTO and comparable agencies in many foreign jurisdictions give third parties an opportunity to oppose pending trademark applications and to seek to cancel registered trademarks.
+Added: In addition, the USPTO and comparable agencies in many foreign jurisdictions give third parties an opportunity to oppose pending trademark applications and to seek to cancel registered trademarks.
Opposition or cancellation proceedings may be filed against our trademarks, and our trademarks may not survive such proceedings.
Moreover, any name we propose to use with our product candidates in the United States must be approved by the FDA, and similarly in many foreign jurisdictions regardless of whether we have registered it, or applied to register it, as a trademark.
−Removed: The FDA typically conducts a review of proposed product names, including an
−Removed: evaluation of potential for confusion with other product names.
+Added: The FDA typically conducts a review of proposed product names, including an evaluation of potential for confusion with other product names.
If the FDA or a foreign regulatory authority objects to any of our proposed proprietary product names, we may be required to expend significant additional resources in an effort to identify a suitable substitute name that would qualify under applicable trademark laws, not infringe the existing rights of third parties and be acceptable to the FDA or other regulatory authorities.
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These parties may breach or terminate these agreements or may refuse to enter into such agreements with us, and we may not have adequate remedies for such breaches.
−Removed: Furthermore, these agreements may not provide meaningful protection for our trade secrets or other proprietary information or result in the effective assignment to us of intellectual property and may not provide an adequate remedy in the event of unauthorized use or disclosure of confidential information or other breaches of the agreements.
+Added: Furthermore, these agreements may not provide meaningful protection for our trade secrets or other proprietary information or result in
+Added: the effective assignment to us of intellectual property and may not provide an adequate remedy in the event of unauthorized use or disclosure of confidential information or other breaches of the agreements.
Despite our efforts to protect our trade secrets, we or our board members, employees, consultants, contractors or scientific and other advisors may unintentionally or willfully disclose our proprietary information to competitors.
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If our competitors independently develop equivalent knowledge, methods and know-how, we would not be able to assert our trade secrets against them and our business, financial condition and results of operations could be harmed.
−Removed: Changes in U.S.
−Removed: patent law could diminish the value of patents in general, thereby impairing our ability to protect our products.
+Added: Changes in patent law in the U.S.
+Added: and in foreign jurisdictions could diminish the value of patents in general, thereby impairing our ability to protect our products.
As is the case with other biopharmaceutical companies, our success is heavily dependent on intellectual property, particularly patents.
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Patent reform legislation could increase the uncertainties and costs surrounding the prosecution of patent applications and the enforcement or defense of issued patents.
−Removed: The Leahy Smith America Invents Act ("the Leahy Smith Act") enacted in
−Removed: September 2011, brought significant changes to the U.S.
+Added: The Leahy Smith America Invents Act ("the Leahy Smith Act") enacted in September 2011, brought significant changes to the U.S.
patent law system.
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• the initiation of material developments in, or conclusion of, disputes or litigation to enforce or defend any of our intellectual property rights or defend against the intellectual property rights of others;
−Removed: • announcements by us or our commercial partners or competitors of new commercial products, clinical progress (or the lack thereof), significant contracts, commercial relationships, or capital commitments;
+Added: • announcements by us or our commercial partners or competitors of new commercial products, clinical progress (or the lack thereof), significant business developments, contracts, commercial relationships, or capital commitments;
• adverse publicity relating to our markets, including with respect to other products and potential products in such markets;
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• general and industry-specific economic conditions potentially affecting our research and development expenditures;
−Removed: • general economic conditions in the United States and abroad (including the potential failure of the United States Congress to raise the debt ceiling);
+Added: • general market conditions and other factors, including factors unrelated to our operating performance or the operating performance of our competitors, including a global pandemic, or macroeconomic factors such as geopolitical tensions, tariffs, or the outbreak or escalation of hostilities or war;
• changes in the structure of health care payment systems;
• adverse regulatory decisions;
+Added: • changes in investor perceptions of us or our industry;
• trading volume of our common stock;
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Ownership of our common stock is highly concentrated, and it may prevent other stockholders from influencing significant corporate decisions.
−Removed: Entities affiliated with Deerfield Management Company beneficially own or control approximately 38.6% of our outstanding common stock (assuming full exercise of our outstanding pre-funded warrants and no exercise of outstanding options) as of December 31, 2023, on a fully-diluted basis.
+Added: 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.
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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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.
−Removed: 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.
+Added: 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
+Added: 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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In addition, we are subject to the risk that a person or government could allege fraud or other misconduct, even if none occurred.
−Removed: 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.
+Added: If any such actions are
+Added: 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.
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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.
−Removed: For example, in early 2023, several financial institutions closed and were taken into receivership by the Federal Deposit Insurance Corporation
+Added: For example, in early 2023, several financial institutions closed and were taken into receivership by the Federal Deposit Insurance Corporation (“FDIC”).
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.