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What changed in Outlook Therapeutics, Inc.'s 10-K — 2024 vs 2025

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Paragraph-level year-over-year comparison of Outlook Therapeutics, Inc.'s 2024 and 2025 10-K annual filings, covering the Business, Risk Factors, Legal Proceedings, Cybersecurity, MD&A and Market Risk sections. Every new, removed and edited paragraph is highlighted side-by-side so you can see exactly what management changed in the 2025 report.

+572 added−521 removedSource: 10-K (2025-12-19) vs 10-K (2024-12-27)

Top changes in Outlook Therapeutics, Inc.'s 2025 10-K

572 paragraphs added · 521 removed · 403 edited across 6 sections

Item 1. Business

Business — how the company describes what it does

119 edited+40 added−27 removed237 unchanged
Biggest changeHowever, the preliminary data from the trial demonstrated an improvement in vision and the presence of biologic activity, as well as a continued favorable safety profile for ONS-5010/LYTENAVA. 1 Table of Contents The pre-specified non-inferiority endpoint at week 8 set forth in the SPA with the FDA was measured by mean change in best corrected visual acuity (BCVA) from baseline to week 8.
Biggest changeIn November 2024, we reported that ONS-5010/LYTENAVA did not meet the pre-specified non-inferiority endpoint at week 8 set forth in the SPA. However, the data from the trial demonstrated an improvement in vision and the presence of biologic activity, as well as a continued favorable safety profile for ONS-5010/LYTENAVA.
In the intent-to-treat, or ITT, primary dataset, the percentage of patients who gained at least 15 letters who were treated with ONS-5010/LYTENAVA, was 41.7%, and the percentage of patients who gained at least 15 letters who were treated with ranibizumab was 23.1% (p = 0.0052).
In the intent-to-treat, or ITT, primary dataset, the percentage of patients who gained at least 15 letters who were treated with ONS-5010/LYTENAVA, was 41.7%, and the percentage of patients who gained at least 15 letters who were treated with ranibizumab was 23.1% (p = 0.0052).
The primary endpoint was also statistically significant and clinically relevant in the secondary per-protocol, or PP dataset (p = 0.04) where the percentages were almost identical, at 41.0% with ONS-5010/LYTENAVA, and 24.7% with ranibizumab.
The primary endpoint was also statistically significant and clinically relevant in the secondary per-protocol, or PP dataset (p = 0.04) where the percentages were almost identical, at 41.0% with ONS-5010/LYTENAVA, and 24.7% with ranibizumab.
The key secondary endpoint BCVA score change from baseline to month 11 in the primary ITT dataset was also highly statistically significant and clinically relevant (p = 0.0035). A mean change of 11.2 letters in BCVA score was observed with ONS-5010/LYTENAVA, and with ranibizumab the mean change was 5.8 letters.
The key secondary endpoint BCVA score change from baseline to month 11 in the primary ITT dataset was also highly statistically significant and clinically relevant (p = 0.0035). A mean change of 11.2 letters in BCVA score was observed with ONS-5010/LYTENAVA, and with ranibizumab the mean change was 5.8 letters.
The results were also statistically significant in the secondary PP dataset (p = 0.01) with a mean change with ONS-5010/LYTENAVA of 11.1 letters versus 7.0 letters with ranibizumab.
The results were also statistically significant in the secondary PP dataset (p = 0.01) with a mean change with ONS-5010/LYTENAVA of 11.1 letters versus 7.0 letters with ranibizumab.
If successful, this study will support the submission of a supplemental BLA to the FDA after ONS-5010/LYTENAVA is approved for wet AMD. NORSE EIGHT NORSE EIGHT is a randomized, controlled, parallel-group, masked non-inferiority study of neovascular age-related macular degeneration subjects randomized in a 1:1 ratio to receive 1.25 mg ONS-5010/LYTENAVA or 0.5 mg ranibizumab intravitreal injections.
If successful, this study will support the submission of a supplemental BLA to the FDA after ONS-5010/LYTENAVA is approved for wet AMD. NORSE EIGHT NORSE EIGHT was a randomized, controlled, parallel-group, masked non-inferiority study of neovascular age-related macular degeneration subjects randomized in a 1:1 ratio to receive 1.25 mg ONS-5010/LYTENAVA or 0.5 mg ranibizumab intravitreal injections.
The difference in the means between the ONS-5010/LYTENAVA and ranibizumab in the NORSE EIGHT trial was -2.257 BCVA letters with a 95% confidence interval of (-4.044, -0.470) while the lower bound of the pre-specified non-inferiority margin in the SPA was -3.5 at a 95% confidence interval; the hypothesis of noninferiority was not met (p>0.025).
The difference in the means between the ONS-5010/LYTENAVA and ranibizumab arms in the NORSE EIGHT trial was -2.257 BCVA letters with a 95% confidence interval of (-4.044, -0.470) while the lower bound of the pre-specified non-inferiority margin in the SPA was -3.5 at a 95% confidence interval; the hypothesis of noninferiority was not met (p>0.025).
In December 2023, we submitted a Special Protocol Assessment, or SPA, to the FDA for this trial (NORSE EIGHT) seeking confirmation that, if successful, it would address the FDA’s requirement for a second adequate and well-controlled clinical trial to support our planned resubmission of the ONS-5010/LYTENAVA BLA.
In December 2023, we submitted a Special Protocol Assessment, or SPA, to the FDA for this study (NORSE EIGHT) seeking confirmation that, if successful, it would address the FDA’s requirement for a second adequate and well-controlled clinical trial to support our planned resubmission of the ONS-5010/LYTENAVA BLA.
If granted, patents issuing from these eight applications are expected to expire in 2036, absent any adjustments or extensions. Our fourth PCT application was nationalized in July 2018 in Australia, Canada, China, Europe, India, Japan, Mexico and the United States. If granted, patents issuing from these eight applications are expected to expire in 2037, absent any adjustments or extensions.
Our fourth PCT application was nationalized in July 2018 in Australia, Canada, China, Europe, India, Japan, Mexico and the United States. If granted, patents issuing from these eight applications are expected to expire in 2037, absent any adjustments or extensions.
However, although multiple branded drugs have been approved for these indications (e.g., LUCENTIS, EYLEA, EYLEA HD, BEOVU, SUSVIMO and VABYSMO), they are very expensive. The recently approved biosimilar versions of LUCENTIS and EYLEA are also expensive, although they are available at a discount to the reference drug.
However, although multiple branded drugs have been approved for these indications (e.g., LUCENTIS, EYLEA, EYLEA HD, BEOVU, SUSVIMO and VABYSMO), they are expensive. The recently approved biosimilar versions of LUCENTIS and EYLEA are also expensive, although they are available at a discount to the reference drug.
Clinical trials involve the administration of the investigational product to human subjects under the supervision of qualified investigators in accordance with GCPs, which include the requirement that all research subjects provide their informed consent for their participation in any clinical study.
Clinical trials involve the administration of the investigational product to human subjects under the supervision of qualified investigators in accordance with GCPs, which include the requirement that all research subjects provide their informed consent in writing for their participation in any clinical study.
The process required by the FDA before biologic product candidates may be marketed in the United States generally involves the following: ● completion of preclinical laboratory tests and animal studies performed in accordance with the FDA’s current Good Laboratory Practices, or GLP, regulation; ● submission to the FDA of an IND, which must become effective before clinical trials may begin and must be updated annually or when significant changes are made; ● approval by an independent Institutional Review Board, or IRB, or ethics committee at each clinical site before the trial is commenced; ● performance of adequate and well-controlled human clinical trials to establish the safety, purity and potency of the proposed biologic product candidate for its intended purpose; ● preparation of and submission to the FDA of a BLA after completion of all pivotal clinical trials; ● a determination by the FDA within 60 days of its receipt of a BLA to file the application for review; ● satisfactory completion of an FDA Advisory Committee review, if applicable; 13 Table of Contents ● satisfactory completion of an FDA pre-approval inspection of the manufacturing facility or facilities at which the proposed product is produced to assess compliance with cGMP and to assure that the facilities, methods and controls are adequate to preserve the biological product’s continued safety, purity and potency, and of selected clinical investigation sites to assess compliance with Good Clinical Practices, or GCP; and ● FDA review and approval of the BLA to permit commercial marketing of the product for particular indications for use in the United States.
The process required by the FDA before biologic product candidates may be marketed in the United States generally involves the following: ● completion of preclinical laboratory tests and animal studies performed in accordance with the FDA’s current Good Laboratory Practices, or GLP, regulation; ● submission to the FDA of an IND application, which must become effective before clinical trials may begin and must be updated annually or when significant changes are made; ● approval by an independent Institutional Review Board, or IRB, or ethics committee at each clinical site before the trial is commenced; ● performance of adequate and well-controlled human clinical trials to establish the safety and effectiveness of the proposed biologic product candidate for its intended purpose; ● preparation of and submission to the FDA of a BLA after completion of all pivotal clinical trials; ● a determination by the FDA within 60 days of its receipt of a BLA to file the application for review; ● satisfactory completion of an FDA Advisory Committee review, if applicable; ● satisfactory completion of an FDA pre-approval inspection of the manufacturing facility or facilities at which the proposed product is produced to assess compliance with cGMP and to assure that the facilities, methods and controls are adequate to preserve the biological product’s continued safety, purity and potency, and of selected clinical investigation sites to assess compliance with Good Clinical Practices, or GCP; and ● FDA review and approval of the BLA to permit commercial marketing of the product for particular indications for use in the United States.
These obligations may include limiting personal data processing to only what is necessary for specified, explicit, and legitimate purposes; requiring a legal basis for personal data processing; requiring the appointment of a data protection officer in certain circumstances; increasing transparency obligations to data subjects; requiring data protection impact assessments in certain circumstances; limiting the collection and retention of personal data; increasing rights for data subjects; formalizing a heightened and codified standard of data subject consents; requiring the implementation and maintenance of technical and organizational safeguards for personal data; mandating notice of certain personal data breaches to the relevant supervisory authority(ies) and affected individuals; and mandating the appointment of representatives in the UK and/or the EU in certain circumstances. ​ Additional Regulation In addition to the foregoing, state and federal laws regarding environmental protection and hazardous substances, including the Occupational Safety and Health Act, the Resource Conservancy and Recovery Act and the Toxic Substances Control Act, affect our business.
These obligations may include limiting personal data processing to only what is necessary for specified, explicit, and legitimate purposes; requiring a legal basis for personal data processing; requiring the appointment of a data protection officer in certain circumstances; increasing transparency obligations to data subjects; 25 Table of Contents requiring data protection impact assessments in certain circumstances; limiting the collection and retention of personal data; increasing rights for data subjects; formalizing a heightened and codified standard of data subject consents; requiring the implementation and maintenance of technical and organizational safeguards for personal data; mandating notice of certain personal data breaches to the relevant supervisory authority(ies) and affected individuals; and mandating the appointment of representatives in the UK and/or the EU in certain circumstances. ​ Additional Regulation In addition to the foregoing, state and federal laws regarding environmental protection and hazardous substances, including the Occupational Safety and Health Act, the Resource Conservancy and Recovery Act and the Toxic Substances Control Act, affect our business.
We seek to protect our proprietary technologies by, among other methods, evaluating relevant patents, establishing defensive positions, monitoring EU oppositions and pending intellectual property rights, preparing litigation strategies in view of the U.S. legislative framework and filing U.S. and international patent applications on technologies, inventions and improvements that are important to our business.
We seek to protect our proprietary technologies by, among other methods, evaluating relevant patents, establishing defensive positions, monitoring EU oppositions and pending intellectual property rights, preparing litigation strategies in view of the U.S. legislative framework and filing United States and international patent applications on technologies, inventions and improvements that are important to our business.
The Affordable Care Act, among other things, via the Physician Payments Sunshine Act, imposes annual reporting requirements on certain manufacturers of drugs, devices, biologics, and medical supplies for which payment is available under Medicare, Medicaid, or the Children’s Health Insurance Program, with specific exceptions, for payments made by them to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors), certain other health care providers (such as physicians assistants and nurse practitioners) and teaching hospitals, as well as ownership and investment interests held by physicians and their immediate family members.
The Affordable Care Act, among other things, via the Physician Payments Sunshine Act, imposes annual reporting requirements on certain manufacturers of drugs, devices, biologics, and medical supplies for which payment is available under Medicare, Medicaid, or the Children’s Health Insurance Program, with specific exceptions, for payments made by them to physicians (defined to include doctors, dentists, optometrists, podiatrists and 17 Table of Contents chiropractors), certain other health care providers (such as physicians assistants and nurse practitioners) and teaching hospitals, as well as ownership and investment interests held by physicians and their immediate family members.
We have continued our approach of working closely with regulatory authorities to develop and conduct clinical trials that we believe will appropriately support approval of ONS-5010/LYTENAVA outside the EU and UK. ● Leveraging the expertise of large partners in the biopharma industry to support launch of ONS-5010/LYTENAVA in the EU and UK, and outside of these countries if the product is approved in other territories.
We have continued our approach of working closely with regulatory authorities to develop and conduct clinical trials that we believe will appropriately support approval of ONS-5010/LYTENAVA outside the EU and UK. ● Leveraging the expertise of partners in the biopharma and ophthalmic industry to support launch of ONS-5010/LYTENAVA in the EU and UK, and outside of these countries if the product is approved in other territories.
As agreed to with the FDA in the SPA, NORSE EIGHT is a randomized, controlled, parallel-group, masked, non-inferiority study of approximately 400 newly diagnosed, wet AMD subjects randomized in a 1:1 ratio to receive 1.25 mg ONS-5010/LYTENAVA or 0.5 mg ranibizumab intravitreal injections.
NORSE EIGHT As agreed to with the FDA in the SPA, NORSE EIGHT was a randomized, controlled, parallel-group, masked, non-inferiority study of approximately 400 newly diagnosed, wet AMD subjects randomized in a 1:1 ratio to receive 1.25 mg ONS-5010/LYTENAVA or 0.5 mg ranibizumab intravitreal injections.
In January 2024, we received confirmation from the FDA that, if successful, this study will address the FDA’s requirement for a second adequate and well-controlled clinical trial to support the resubmission of the ONS-5010/LYTENAVA BLA for wet AMD. ​ A total of 400 patients were enrolled in the study.
In January 2024, we received confirmation from the FDA that, if successful, this study would address the FDA’s requirement for a second adequate and well-controlled clinical trial to support the resubmission of the ONS-5010/LYTENAVA BLA for wet AMD. ​ A total of 400 patients were enrolled in the study.
However, if the conditions are not fulfilled within the timeframe set by the EMA and approved by the European Commission, the MA will cease to be renewed. ​ An MA may also be granted “under exceptional circumstances” where the applicant can show that it is unable to provide comprehensive data on efficacy and safety under normal conditions of use even after the product has been authorized and subject to specific procedures being introduced.
However, if the conditions are not fulfilled within the timeframe set by the EMA and approved by the European Commission, the MA will cease to be renewed. ​ 21 Table of Contents An MA may also be granted “under exceptional circumstances” where the applicant can show that it is unable to provide comprehensive data on efficacy and safety under normal conditions of use even after the product has been authorized and subject to specific procedures being introduced.
Once the MA is obtained in all EU Member States and study results are included in the product information, even when negative, the product is eligible for a six-month extension to the Supplementary Protection Certificate, or SPC, if any is in effect at the time of authorization or, in the case of orphan medicinal products, a two-year extension of orphan market exclusivity. ​ 22 Table of Contents Manufacturing Regulation in the EU ​ In addition to an MA, various other requirements apply to the manufacturing and placing on the EU market of medicinal products.
Once the MA is obtained in all EU Member States and study results are included in the product information, even when negative, the product is eligible for a six-month extension to the Supplementary Protection Certificate, or SPC, if any is in effect at the time of authorization or, in the case of orphan medicinal products, a two-year extension of orphan market exclusivity. ​ Manufacturing Regulation in the EU ​ In addition to an MA, various other requirements apply to the manufacturing and placing on the EU market of medicinal products.
In addition, we have the right to terminate each of the commercial agreements at 10 Table of Contents any time for our convenience; however, with respect to the agreements relating to ONS-3010 and ONS-1045, this right is subject to the consent of Laboratories Liomont, S.A. de C.V., or Liomont (a licensing partner in Mexico for ONS-3010 and ONS-1045) pursuant to a corresponding letter we executed in conjunction with the standby agreement entered into between Selexis and Liomont on November 11, 2014.
In addition, we have the right to terminate each of the commercial agreements at any time for our convenience; however, with respect to the agreements relating to ONS-3010 and ONS-1045, this right is subject to the consent of Laboratories Liomont, S.A. de C.V., or Liomont (a licensing partner in Mexico for ONS-3010 and ONS-1045) pursuant to a corresponding letter we executed in conjunction with the standby agreement entered into between Selexis and Liomont on November 11, 2014.
Regulatory Government Regulation and Product Approval The FDA and other regulatory authorities at federal, state, and local levels, as well as in foreign countries, extensively regulate, among other things, the research, development, testing, manufacture, quality control, import, export, safety, effectiveness, labeling, packaging, storage, distribution, record keeping, approval, advertising, promotion, marketing, post-approval monitoring, and post-approval reporting of biologics such as those we are developing.
Regulatory Government Regulation and Product Approval The FDA and other regulatory authorities at federal, state, and local levels, as well as in foreign countries, extensively regulate, among other things, the research, development, testing, manufacture, quality control, import, export, safety, 12 Table of Contents effectiveness, labeling, packaging, storage, distribution, record keeping, approval, advertising, promotion, marketing, post-approval monitoring, and post-approval reporting of biologics such as those we are developing.
The federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, created additional federal criminal statutes that prohibit, among other actions, knowingly and willfully executing, or attempting to execute, a scheme to defraud any healthcare benefit program, including private third-party payors, knowingly and willfully embezzling or stealing from a healthcare benefit program, willfully obstructing a criminal investigation of a healthcare offense, and knowingly and willfully falsifying, concealing or covering up a material fact or making any materially false, fictitious or fraudulent statement in connection with the delivery of or payment for healthcare benefits, items or services.
The federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, created additional federal criminal statutes that prohibit covered entities and business associates from, among other actions, knowingly and willfully executing, or attempting to execute, a scheme to defraud any healthcare benefit program, including private third-party payors, knowingly and willfully embezzling or stealing from a healthcare benefit program, willfully obstructing a criminal investigation of a healthcare offense, and knowingly and willfully falsifying, concealing or covering up a material fact or making any materially false, fictitious or fraudulent statement in connection with the delivery of or payment for healthcare benefits, items or services.
There are also requirements governing the reporting of ongoing clinical studies and clinical study results to public registries. For purposes of BLA approval, human clinical trials are typically conducted in three sequential phases that may overlap. ● Phase 1 — The investigational product is initially introduced into healthy human subjects or patients with the target disease or condition.
There are also requirements governing the reporting of ongoing clinical studies and clinical study results to public registries, including clinicaltrials.gov. For purposes of BLA approval, human clinical trials are typically conducted in three sequential phases that may overlap. ● Phase 1 — The investigational product is initially introduced into healthy human subjects or patients with the target disease or condition.
However, because there is no FDA approved ophthalmic formulation of bevacizumab in the United States, and there was previously no approved ophthalmic formulation of bevacizumab in the EU or UK until the marketing authorizations of ONS-5010/LYTENAVA in the EU and UK , doctors have used repackaged bevacizumab (Avastin) provided by compounding pharmacists that is not required to meet the standards for ophthalmic 8 Table of Contents use necessary for an approved product.
However, because there is no FDA approved ophthalmic formulation of bevacizumab in the United States, and there was previously no approved ophthalmic formulation of bevacizumab in the EU or UK until the marketing authorizations of ONS-5010/LYTENAVA in the EU and UK , doctors have used repackaged bevacizumab (Avastin) provided by compounding pharmacists that is not required to meet the standards for ophthalmic use necessary for an approved product.
Later discovery of previously unknown problems with a product, including adverse events of unanticipated severity or frequency, or with manufacturing processes, or failure to comply with regulatory requirements, may result in revisions to the approved labeling to add new safety information; imposition of post-market studies or clinical studies to assess new safety risks; or imposition of distribution restrictions or other restrictions under a REMS program.
Later discovery of previously unknown problems with a product, including adverse events of unanticipated severity or frequency, or with manufacturing processes, or failure to comply 15 Table of Contents with regulatory requirements, may result in revisions to the approved labeling to add new safety information; imposition of post-market studies or clinical studies to assess new safety risks; or imposition of distribution restrictions or other restrictions under a REMS program.
In the EU, clinical trials are governed by the Clinical Trials Regulation (EU) No 536/2014, or CTR, which entered into application on January 31, 2022 repealing and replacing the former Clinical Trials Directive 2001/20, or CTD. ​ The CTR is intended to harmonize and streamline clinical trial authorizations, simplify adverse-event reporting procedures, improve the supervision of clinical trials and increase transparency.
In the EU, clinical trials are governed by the Clinical Trials Regulation (EU) No 536/2014, or CTR, 19 Table of Contents which entered into application on January 31, 2022 repealing and replacing the former Clinical Trials Directive 2001/20, or CTD. ​ The CTR is intended to harmonize and streamline clinical trial authorizations, simplify adverse-event reporting procedures, improve the supervision of clinical trials and increase transparency.
However, there is no guarantee that a product will be considered by the EU’s regulatory authorities to be a new chemical/biological entity, and products may not qualify for data exclusivity. ​ [In the EU, there is a special regime for biosimilars, or biological medicinal products that are similar to a reference medicinal product but that do not meet the definition of a generic medicinal product.
However, there is no 22 Table of Contents guarantee that a product will be considered by the EU’s regulatory authorities to be a new chemical/biological entity, and products may not qualify for data exclusivity. ​ [In the EU, there is a special regime for biosimilars, or biological medicinal products that are similar to a reference medicinal product but that do not meet the definition of a generic medicinal product.
Per the American Academy of Ophthalmology, retinal vein occlusions are the second most common retinal vascular disorder after diabetic retinopathy. There were an estimated 0.3 million patients with BRVO in the United States, European countries and Japan alone in 2020 (Triangulation 4 Table of Contents of Global Data, Market Scope and Investor Forecasts (2020)).
Per the American Academy of Ophthalmology, retinal vein occlusions are the second most common retinal vascular disorder after diabetic retinopathy. There were an estimated 0.3 million patients with BRVO in the United States, European countries and Japan alone in 2020 (Triangulation of Global Data, Market Scope and Investor Forecasts (2020)).
For example, in March 2010, President Obama signed into law the Affordable Care Act, which among other things, expanded coverage for the uninsured while at the same time containing overall healthcare costs, expanded and increased industry rebates for drugs covered under Medicaid programs, and made changes to the coverage requirements under the Medicare prescription drug benefit.
For example, in March 2010, the Affordable Care Act was signed into law, which among other things, expanded coverage for the uninsured while at the same time containing overall healthcare costs, expanded and increased industry rebates for drugs covered under Medicaid programs, and made changes to the coverage requirements under the Medicare prescription drug benefit.
Subjects will be treated for three months, and the enrollment of subjects in the arm of the study receiving ONS-5010/LYTENAVA in vials has been completed. 5 Table of Contents NORSE ONE NORSE ONE was designed as a randomized, masked clinical experience trial to support our BLA submission with the FDA for ONS-5010/LYTENAVA for the treatment of wet AMD.
Subjects will be treated for three months, and the enrollment of subjects in the arm of the study receiving ONS-5010/LYTENAVA in vials has been completed. NORSE ONE NORSE ONE was designed as a randomized, masked clinical experience trial to support our BLA submission with the FDA for ONS-5010/LYTENAVA for the treatment of wet AMD.
Clinical trials are conducted under protocols detailing, among other things, the objectives of the study, the parameters to be used in monitoring safety and the effectiveness criteria to be evaluated. A separate submission to the existing IND must be made for each successive clinical trial conducted during product development and for any subsequent protocol amendments.
Clinical trials are conducted under protocols detailing, among other things, the objectives of the study, the parameters to be used in monitoring safety and the effectiveness criteria 13 Table of Contents to be evaluated. A separate submission to the existing IND must be made for each successive clinical trial conducted during product development and for any subsequent protocol amendments.
We are also planning to develop ONS-5010/LYTENAVA for use in the treatment of other retina diseases such as DME and BRVO. We continue to hold the developed market commercialization rights for two legacy biosimilar product candidates, but currently have no plans to further develop these assets .
We are also planning to develop and generate evidence to support ONS-5010/LYTENAVA for use in the treatment of other retina diseases such as DME and BRVO. We continue to hold the developed market commercialization rights for two legacy biosimilar product candidates but currently have no plans to further develop these assets .
These clinical trials are intended to establish the overall risk/benefit ratio of the investigational product and to provide an adequate basis for product approval. 14 Table of Contents In some cases, the FDA may require, or companies may voluntarily pursue, additional clinical trials after a product is approved to gain more information about the product.
These clinical trials are intended to establish the overall risk/benefit ratio of the investigational product and to provide an adequate basis for product approval. In some cases, the FDA may require, or companies may voluntarily pursue, additional clinical trials after a product is approved to gain more information about the product.
In addition, many biotechnology companies have formed collaborations with large, established companies to support research, development and commercialization of products that may be competitive with ours, and we may also compete against other biotechnology companies in our efforts to find a potential strategic partner for ONS-5010/LYTENAVA.
In addition, many biotechnology companies have formed 10 Table of Contents collaborations with large, established companies to support research, development and commercialization of products that may be competitive with ours, and we may also compete against other biotechnology companies in our efforts to find a potential strategic partner for ONS-5010/LYTENAVA.
The FDA also may condition approval on, among other things, changes to proposed labeling or the development of adequate controls and specifications. Once approved, the FDA may withdraw the product approval if compliance with pre- and post-marketing requirements is not maintained or if problems occur after the product reaches 15 Table of Contents the marketplace.
The FDA also may condition approval on, among other things, changes to proposed labeling or the development of adequate controls and specifications. Once approved, the FDA may withdraw the product approval if compliance with pre- and post-marketing requirements is not maintained or if problems occur after the product reaches the marketplace.
Applications should be decided within a maximum of 60 days if there are no major objections identified that cannot be resolved within such 60 day period and the approval from the 24 Table of Contents trusted regulatory partner selected has been granted within the previous 2 years or if there are such major objections identified or such approval hasn’t been granted within the previous 2 years within 110 days.
Applications should be decided within a maximum of 60 days if there are no major objections identified that cannot be resolved within such 60 day period and the approval from the trusted regulatory partner selected has been granted within the previous 2 years or if there are such major objections identified or such approval hasn’t been granted within the previous 2 years within 110 days.
NORSE THREE was an open-label safety study we conducted to ensure the adequate number of safety exposures to ONS-5010/LYTENAVA were available for the initial ONS-5010/LYTENAVA BLA submission with the FDA. In March 2021, we reported that the results from NORSE 2 Table of Contents THREE showed a positive safety profile for ONS-5010/LYTENAVA.
NORSE THREE was an open-label safety study we conducted to ensure the adequate number of safety exposures to ONS-5010/LYTENAVA were available for the initial ONS-5010/LYTENAVA BLA submission with the FDA. In March 2021, we reported that the results from NORSE THREE showed a positive safety profile for ONS-5010/LYTENAVA.
To obtain an MA for a product in the EU, an applicant must submit a Marketing Authorization Application, or MAA, either under a centralized procedure administered by the European Medicines Agency, or EMA, or one of the 20 Table of Contents procedures administered by the competent authorities of EU Member States (decentralized procedure, national procedure or mutual recognition procedure).
To obtain an MA for a product in the EU, an applicant must submit a Marketing Authorization Application, or MAA, either under a centralized procedure administered by the European Medicines Agency, or EMA, or one of the procedures administered by the competent authorities of EU Member States (decentralized procedure, national procedure or mutual recognition procedure).
It is a three month study designed to compare the safety of ophthalmic bevacizumab in vials versus 7 Table of Contents pre-filled syringes in subjects diagnosed with a retinal condition that would benefit from treatment with intravitreal injection of bevacizumab, including exudative AMD, DME, or BRVO.
It is a three month study designed to compare the safety of ophthalmic bevacizumab in vials versus pre-filled syringes in subjects diagnosed with a retinal condition that would benefit from treatment with intravitreal injection of bevacizumab, including exudative AMD, DME, or BRVO.
The federal government has used the civil False Claims Act, 17 Table of Contents and the accompanying threat of significant liability, in its investigation and prosecution of pharmaceutical and biotechnology companies throughout the country, for example, in connection with the promotion of products for unapproved uses and other illegal sales and marketing practices.
The federal government has used the civil False Claims Act, and the accompanying threat of significant liability, in its investigation and prosecution of pharmaceutical and biotechnology companies throughout the country, for example, in connection with the promotion of products for unapproved uses and other illegal sales and marketing practices.
Upon formation of the PRC joint venture in April 2021, we entered into a royalty-free license with the PRC joint venture for the development, 9 Table of Contents commercialization and manufacture of ONS-5010/LYTENAVA in the greater China market, which includes Hong Kong, Taiwan and Macau.
Upon formation of the PRC joint venture in April 2021, we entered into a royalty-free license with the PRC joint venture for the development, commercialization and manufacture of ONS-5010/LYTENAVA in the greater China market, which includes Hong Kong, Taiwan and Macau.
General requirements for advertising and promotion of medicinal products, such as direct-to-consumer advertising of prescription medicinal products are established in EU law. 23 Table of Contents However, the details are governed by regulations in individual EU Member States and can differ from one country to another.
General requirements for advertising and promotion of medicinal products, such as direct-to-consumer advertising of prescription medicinal products are established in EU law. However, the details are governed by regulations in individual EU Member States and can differ from one country to another.
In addition, we are required to pay a single-digit royalty on a final product-by-final product and country-by-country basis, based on worldwide net sales of such final products by us or any of our affiliates or sublicensees during the royalty term.
In addition, we are required to pay a single-digit royalty on a final product-by-final product and 9 Table of Contents country-by-country basis, based on worldwide net sales of such final products by us or any of our affiliates or sublicensees during the royalty term.
Our registration plan for wet AMD, the initial indication planned for ONS-5010/LYTENAVA, consisted of three clinical trials which we refer to as NORSE ONE, NORSE TWO and NORSE THREE. All three clinical trials have been completed. We reported achieving the anticipated safety and efficacy and positive proof-of-concept topline results from NORSE ONE, a clinical experience study, in August 2020.
Our registration plan for wet AMD, the initial indication planned for ONS-5010/LYTENAVA, consisted of three clinical trials which we refer to as NORSE ONE, NORSE TWO and NORSE THREE. We reported achieving the anticipated safety and efficacy and positive proof-of-concept topline results from NORSE ONE, a clinical experience study, in August 2020.
The primary endpoint is the mean change in BCVA from baseline to Week 8. Subjects received injections at Day 0 (randomization), Week 4, and Week 8 visits.
The primary endpoint was the mean change in BCVA from baseline to Week 8. Subjects received injections at Day 0 (randomization), Week 4, and Week 8 visits.
Preclinical and Clinical Development Prior to beginning the first clinical trial with a product candidate in the United States, we must submit an IND to the FDA. An IND is a request for authorization from the FDA to administer an investigational new drug product to humans.
Preclinical and Clinical Development Prior to beginning the first clinical trial with a product candidate in the United States, we must submit an IND to the FDA. An IND is a request for authorization from the FDA to administer an investigational new drug product (including biological products) to humans.
In October 2023, the MHRA announced a new Notification Scheme for clinical trials which enables a more streamlined and risk-proportionate approach to initial clinical trial applications for Phase 4 and low-risk Phase 3 clinical trial applications. ​ Marketing authorizations in the UK are governed by the Human Medicines Regulations (SI 2012/1916), as amended.
In October 2023, the MHRA announced a new Notification Scheme for clinical trials which enables a more streamlined and risk-proportionate approach to initial clinical trial applications for Phase 4 and low-risk Phase 3 clinical trial applications. 23 Table of Contents ​ Marketing authorizations in the UK are governed by the Human Medicines Regulations (SI 2012/1916), as amended.
In addition, the U.S. government, state legislatures and foreign governments have continued implementing cost-containment programs, including price controls, restrictions on coverage and reimbursement and requirements for substitution of generic products. Adoption of price controls and cost-containment measures and adoption of more restrictive policies in jurisdictions with existing controls and measures could further limit our net revenue and results.
In addition, the United States government, state legislatures and foreign governments have continued implementing cost-containment programs, including price controls, restrictions on coverage and reimbursement and requirements for substitution of generic products. Adoption of price controls and cost-containment measures and adoption of more restrictive policies in jurisdictions with existing controls and measures could further limit our net revenue and results.
This Health Technology Assessment, or HTA, process is the procedure according to which the assessment of the public health impact, 25 Table of Contents therapeutic impact and the economic and societal impact of use of a given medicinal product in the national healthcare systems of the individual country is conducted.
This Health Technology Assessment, or HTA, process is the procedure according to which the assessment of the public health impact, therapeutic impact and the economic and societal impact of use of a given medicinal product in the national healthcare systems of the individual country is conducted.
We have also executed a supply agreement for a best-in-class pre-filled ophthalmic syringe, which we believe will provide both ease-of-use for clinicians and add to ONS-5010/LYTENAVA’s safety profile over the current unapproved therapies that have caused problems related to syringe malfunction and contamination. We will screen other contract manufacturers to meet our clinical, commercial and regulatory supply requirements as needed.
We are currently negotiating a supply agreement for a best-in-class pre-filled ophthalmic syringe, which we believe will provide both ease-of-use for clinicians and add to ONS-5010/LYTENAVA’s safety profile over the current unapproved therapies that have caused problems related to syringe malfunction and contamination. We will screen other contract manufacturers to meet our clinical, commercial and regulatory supply requirements as needed.
Pursuant to the IRP, the MHRA will take into account the expertise and decision-making of trusted regulatory partners (e.g. the regulatory in Australia, Canada, Switzerland, Singapore, Japan, the U.S.A. and the EU). The MHRA will conduct a targeted assessment of IRP applications but retain the authority to reject applications if the evidence provided is considered insufficiently robust.
Pursuant to the IRP, the MHRA will take into account the expertise and decision-making of trusted regulatory partners (e.g. the regulatory in Australia, Canada, Switzerland, Singapore, Japan, the United States and the EU). The MHRA will conduct a targeted assessment of IRP applications but retain the authority to reject applications if the evidence provided is considered insufficiently robust.
We intend to leverage their collective experience to further the development of, and execute an optimal commercial strategy for, ONS-5010/LYTENAVA, including licensing commercial rights to ONS-5010/LYTENAVA to a strategic partner outside the United States. ● Engaging with regulatory authorities to establish clear guidelines for potential approval of ONS-5010/LYTENAVA outside the EU and UK.
We intend to leverage their collective experience to further the development of, and execute an optimal commercial strategy for, ONS-5010/LYTENAVA, including potentially licensing commercial rights to ONS-5010/LYTENAVA to a strategic partner in some countries outside the United States. ● Engaging with regulatory authorities to establish clear guidelines for potential approval of ONS-5010/LYTENAVA outside the EU and UK.
Additionally, the federal false claims and civil monetary penalties laws, including the civil False Claims Act prohibit, among other things, knowingly presenting or causing the presentation of a false, fictitious or fraudulent claim for payment to the U.S. government, or making a false statement to avoid, decrease, or conceal an obligation to pay money to the federal government.
Additionally, the federal false claims and civil monetary penalties laws, including the civil False Claims Act prohibit, among other things, knowingly presenting or causing the presentation of a false, fictitious or fraudulent claim for payment to the United States government, or making a false statement to avoid, decrease, or conceal an obligation to pay money to the federal government.
Wet AMD is the advanced form of macular degeneration that involves the formation of abnormal and leaky blood vessels in the back of the eye behind the retina, through a process known as 11 Table of Contents choroidal neovascularization.
Wet AMD is the advanced form of macular degeneration that involves the formation of abnormal and leaky blood vessels in the back of the eye behind the retina, through a process known as choroidal neovascularization.
Our second PCT application was nationalized in July 2017 in Europe and the United States. If granted, patents issuing from these two applications are expected to expire in 2036, absent any adjustments or extensions. Our third PCT application was nationalized in June 2018 in Australia, Canada, China, Europe, India, Japan, Mexico and the United States.
If granted, patents issuing from these two applications are expected to expire in 2036, absent any adjustments or extensions. Our third PCT application was nationalized in June 2018 in Australia, Canada, China, Europe, India, Japan, Mexico and the United States. If granted, patents issuing from these eight applications are expected to expire in 2036, absent any adjustments or extensions.
The safety results demonstrated in NORSE EIGHT are consistent with previously reported safety results from the NORSE ONE, NORSE TWO, and NORSE THREE clinical trials, with no cases of retinal vasculitis reported in either study arm.
The safety results demonstrated across the full duration of NORSE EIGHT are consistent with previously reported safety results from the NORSE ONE, NORSE TWO, and NORSE THREE clinical trials, with no cases of retinal vasculitis reported in either study arm.
Further, there is no uniform policy for coverage and reimbursement in the United States. Third-party payors often rely upon Medicare coverage policy and payment limitations in setting their own reimbursement rates, but also have their own methods and approval process apart from Medicare determinations.
Further, there is no uniform policy for coverage and reimbursement in the United 24 Table of Contents States. Third-party payors often rely upon Medicare coverage policy and payment limitations in setting their own reimbursement rates, but also have their own methods and approval process apart from Medicare determinations.
On August 29, 2023, we received a Complete Response Letter, or CRL, in which the FDA concluded it could not approve the BLA during this review cycle due to several chemical, manufacturing and control, or CMC, issues, open observations from pre-approval manufacturing inspections, and a lack of substantial evidence.
In August 2023, we received a Complete Response Letter, or CRL, in which the FDA concluded it could not approve the BLA during this review cycle due to several chemical, manufacturing and control, or CMC, issues, open observations from pre-approval manufacturing inspections, and a lack of substantial 1 Table of Contents evidence.
If the CHMP accepts a request for accelerated assessment, the time limit of 210 days will be reduced to 150 days (excluding clock stops).
If the CHMP accepts a request for accelerated assessment, the time limit of 210 days 20 Table of Contents will be reduced to 150 days (excluding clock stops).
Our business could be harmed if our current contract manufacturer is unable to manufacture our product candidates at the necessary quantity or quality levels, We currently engage single source suppliers for clinical trial services and multiple source suppliers for future drug substance manufacturing, fill-finish manufacturing and product testing of ONS-5010/LYTENAVA.
Our business could be harmed if our current contract manufacturer is unable to manufacture our product candidates at the necessary quantity or quality levels, We currently engage single source suppliers for clinical trial services, drug substance manufacturing, and fill-finish manufacturing of ONS-5010/LYTENAVA. The loss of any of these suppliers, or any future single source suppliers, could harm our business.
To meet this retinal market need, we are developing ONS-5010/LYTENAVA as an investigational ophthalmic formulation of bevacizumab in the United States.
To meet this retinal market need, we developed ONS-5010/LYTENAVA as an investigational ophthalmic formulation of bevacizumab in the United States.
Our first PCT application was nationalized in April 2016 in Australia, Canada, China, Europe, Hong Kong, India, Japan, Mexico and the United States. If granted, patents issuing 12 Table of Contents from these nine applications are expected to expire in 2034, absent any adjustments or extensions.
Our first PCT application was nationalized in April 2016 in Australia, Canada, China, Europe, Hong Kong, India, Japan, Mexico and the United States. If granted, patents issuing from these nine applications are expected to expire in 2034, absent any adjustments or extensions. Our second PCT application was nationalized in July 2017 in Europe and the United States.
On August 15, 2024, HHS announced the agreed-upon reimbursement prices of the first ten drugs that were subject to price negotiations, although the Medicare drug price negotiation program is currently subject to legal challenges. HHS will select up to fifteen additional drugs covered under Part D for negotiation in 2025.
On August 15, 2024, HHS announced the agreed-upon reimbursement prices of the first ten drugs that were subject to price negotiations, although the Medicare drug price negotiation program is currently subject to legal challenges. On January 17, 2025, HHS selected fifteen additional products covered under Part D for price negotiation in 2025.
At subsequent Type A meetings with the FDA, we learned that the FDA requires the completion of an additional adequate and well-controlled clinical trial demonstrating the effectiveness of ONS-5010/LYTENAVA in the treatment of nAMD, as well as additional requested CMC data indicated in the CRL to approve ONS-5010/LYTENAVA for use in wet AMD.
At subsequent Type A meetings with the FDA, we learned that the FDA required the completion of an additional adequate and well-controlled clinical trial evaluating ONS-5010/LYTENAVA, as well as additional requested CMC data indicated in the CRL to approve ONS-5010/LYTENAVA for use in wet AMD.
We may incur significant costs to comply with such laws and regulations now or in the future. ​ Employees and Human Capital Resources As of September 30, 2024, we had 23 full-time employees, seven of whom were primarily engaged in research and development activities and five of whom have a Ph.D. degree.
We may incur significant costs to comply with such laws and regulations now or in the future. ​ Employees and Human Capital Resources As of September 30, 2025, we had 17 full-time employees, seven of whom were primarily engaged in research and development activities and commercialization of ONS-5010/LYTENAVA and five of whom have a Ph.D. degree.
Any authorization which is not followed by the actual placing of the medicinal product on the EU market (for a centralized MA) or on the market of the authorizing EU Member State within three years after authorization ceases to be valid (the so-called sunset clause). ​ 21 Table of Contents Innovative products that target an unmet medical need and are expected to be of major public health interest may be eligible for a number of expedited development and review programs, such as the Priority Medicines, or PRIME, scheme, which provides incentives similar to the breakthrough therapy designation in the U.S.
Any authorization which is not followed by the actual placing of the medicinal product on the EU market (for a centralized MA) or on the market of the authorizing EU Member State within three years after authorization ceases to be valid (the so-called sunset clause). ​ Innovative products that target an unmet medical need and are expected to be of major public health interest may be eligible for a number of expedited development and review programs, such as the Priority Medicines, or PRIME, scheme, which provides incentives similar to the breakthrough therapy designation in the United States PRIME is a voluntary scheme aimed at enhancing the EMA’s support for the development of medicinal products that target unmet medical needs.
Since the advent of anti-VEGF therapy, it has become the standard of care treatment option within the retina community, globally. Market Opportunity Age-related macular degeneration, or AMD, is a common eye condition and a leading cause of vision loss among people age 50 and older. Wet AMD is a form of “late stage” AMD and is also called neovascular AMD.
Since the advent of anti-VEGF therapy, it has become the standard of care treatment option within the retina community, globally. 4 Table of Contents Market Opportunity Age-related macular degeneration, or AMD, is a common eye condition and a leading cause of vision loss among people age 50 and older.
We cannot predict what healthcare reform initiatives may be adopted in the future, particularly in light of the U.S. presidential and Congressional elections. The Affordable Care Act, the IRA, as well as other federal, state and foreign healthcare reform measures that have been and may be adopted in the future, could harm our future revenues.
We cannot predict what healthcare reform initiatives may be adopted in the future. The Affordable Care Act, the IRA, as well as other federal, state and foreign healthcare reform measures that have been and may be adopted in the future, could harm our future revenues.
Furthermore, an independent IRB for each site proposing to conduct the clinical trial must review and approve the plan for any clinical trial and its informed consent form before the clinical trial begins at that site and must monitor the study until completed.
Furthermore, an independent IRB for each site proposing to conduct the clinical trial must review and approve the plan for any clinical trial and its informed consent form that must be provided to each trial subject or his or her legal representative before the clinical trial begins at that site and must monitor the study until completed.
Such off-label uses are common across medical specialties. Physicians may believe that such off-label uses are the best treatment for many patients in varied circumstances. The FDA does not regulate the behavior of physicians in their choice of treatments.
Such off-label uses are common across medical specialties. Physicians may believe that such off-label uses are the best treatment for many patients in varied circumstances. The FDA does not regulate the behavior of physicians in their choice of treatments. The FDA does, however, restrict manufacturer’s communications on the subject of off-label use of their products.
Additionally, the IRA, among other things, (i) directs HHS to negotiate the price of certain high-expenditure, single-source drugs and biologics covered under Medicare, and subject drug manufacturers to civil monetary penalties and a potential excise tax by offering a price that is not equal to or less than the negotiated “maximum fair price” under the law, and (ii) imposes rebates under Medicare Part B and Medicare Part D to penalize price increases that outpace inflation.
Department of Health & Human Services, or HHS, to negotiate the price of certain high-expenditure, single-source drugs and biologics covered under Medicare, and subject drug manufacturers to civil monetary penalties and a potential excise tax by offering a price that is not equal to or less than the negotiated “maximum fair price” under the law, and (ii) imposed rebates under Medicare Part B and Medicare Part D to penalize price increases that outpace inflation.
Before approving a BLA, the FDA will typically inspect the facility or facilities where the product is manufactured. The FDA will not approve an application unless it determines that the manufacturing processes and facilities are in compliance with cGMP requirements and adequate to assure consistent production of the product within required specifications.
The FDA will not approve an application unless it determines that the manufacturing processes and facilities are in compliance with cGMP requirements and adequate to assure consistent production of the product within required specifications. Additionally, before approving a BLA, the FDA will typically inspect one or more clinical sites to assure compliance with GCP.
The FDA does, however, restrict manufacturer’s communications on the subject of off-label use of their products. 16 Table of Contents Biosimilars and Reference Product Exclusivity The Patient Protection and Affordable Care Act, as amended by the Health Care and Education Reconciliation Act, or collectively, the Affordable Care Act, signed into law in 2010, includes a subtitle called the Biologics Price Competition and Innovation Act of 2009, or BPCIA, which created an abbreviated approval pathway for biological products that are biosimilar to or interchangeable with an FDA-approved reference biological product.
Biosimilars and Reference Product Exclusivity The Patient Protection and Affordable Care Act, as amended by the Health Care and Education Reconciliation Act, or collectively, the Affordable Care Act, signed into law in 2010, includes a subtitle called the Biologics Price Competition and Innovation Act of 2009, or BPCIA, which created an abbreviated approval pathway for biological products that are biosimilar to or interchangeable with an FDA-approved reference biological product.
In wet AMD, abnormal blood vessels grow underneath the retina. These vessels can leak fluid and blood, which may lead to swelling and damage of the macula causing vision loss. With wet AMD, abnormally high levels of VEGF are secreted in the eyes. VEGF is a protein that promotes the growth of new abnormal blood vessels.
Wet AMD is a form of “late stage” AMD and is also called neovascular AMD. In wet AMD, abnormal blood vessels grow underneath the retina. These vessels can leak fluid and blood, which may lead to swelling and damage of the macula causing vision loss. With wet AMD, abnormally high levels of VEGF are secreted in the eyes.
In November 2021, we began enrolling patients in our NORSE SEVEN clinical trial. The study compares the safety of ophthalmic bevacizumab in vials versus pre-filled syringes in subjects diagnosed with a retinal condition that would benefit from treatment with intravitreal injection of bevacizumab, including exudative age-related macular degeneration, DME, or BRVO.
The study compares the safety of ophthalmic bevacizumab in vials versus pre-filled syringes in subjects diagnosed with a retinal condition that would benefit from treatment with intravitreal injection of bevacizumab, including exudative age-related macular degeneration, DME, or BRVO.
The current FDA approved market leaders for the treatment of wet AMD are VEGF inhibitors, including EYLEA, EYLEA HD, BEOVU, LUCENTIS, SUSVIMO and VABYSMO. Recently, BYOOVIZ and CIMERLI were approved and launched, both ranibizumab biosimilars, as well as PAVBLU, an aflibercept biosimilar.
The current FDA-approved market leaders are VEGF inhibitors, including Eylea ® , Eylea ® HD, Beovu ® , Lucentis ® , Susvimo ® , and Vabysmo ® . Recently, ranibizumab biosimilars BYOOVIZ ® and CIMERLI ® and the aflibercept biosimilar PAVBLU ® were approved and launched.
As part of our multi-year commercial planning process, we entered into a strategic collaboration agreement with Cencora to support the commercial launch of ONS-5010/LYTENAVA globally. Cencora will provide comprehensive launch support in the EU and UK, including pharmacovigilance, regulatory affairs, quality management, market access support, importation, third-party logistics distribution and field solutions.
We have entered into a strategic collaboration agreement with Cencora to support the commercial launch of ONS-5010/LYTENAVA globally. Cencora 7 Table of Contents provides comprehensive launch support in the EU and UK, including pharmacovigilance, regulatory affairs, quality management, market access support, importation, third-party logistics distribution and field solutions.
Because there are no approved bevacizumab products for the treatment of retinal diseases in the United States, we submitted a standard BLA, and are not using the biosimilar drug development pathway that would be required if there were an approved bevacizumab drug for the targeted diseases.
Because there previously were no approved bevacizumab products for the treatment of retinal diseases in the United States and other major markets, we submitted standard biologic therapeutic applications and are not using the biosimilar drug regulatory pathway that would be required if bevacizumab were an approved drug for the targeted disease.
Healthcare Laws and Compliance Requirements Although we currently do not have any products on the market, our current and future arrangements with healthcare professionals, principal investigators, consultants, customers and third-party payors expose us to broadly applicable healthcare regulation and enforcement by the federal government and the states and foreign governments in which we conduct our business.
The BPCIA also created certain exclusivity periods for biosimilars approved as interchangeable products. 16 Table of Contents Other United States Healthcare Laws and Compliance Requirements Although we currently do not have any products on the market, our current and future arrangements with healthcare professionals, principal investigators, consultants, customers and third-party payors expose us to broadly applicable healthcare regulation and enforcement by the federal government and the states and foreign governments in which we conduct our business.

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Item 1A. Risk Factors

Risk Factors — what could go wrong, per management

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Biggest changeAdditional mergers and acquisitions in the pharmaceutical industry may result in even more resources being concentrated in our competitors. As a result, these companies may obtain regulatory approval in countries where we have not yet received approval for ONS-5010/LYTENAVA more rapidly than we are able to and may be more effective in selling and marketing their products.
Biggest changeAs a result, these companies may obtain regulatory approval in countries where we have not yet received approval for ONS-5010/LYTENAVA more rapidly than we are able to and may be more effective in selling and marketing their products. 44 Table of Contents Smaller or early-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large, established companies, and we also compete against such companies for resources from and in securing partnering arrangements with, such large, established companies.
At subsequent Type A meetings with the FDA, we learned that the FDA requires the successful completion of an additional adequate and well-controlled clinical trial evaluating ONS-5010/LYTENAVA, as well as additional requested CMC data indicated in the CRL to approve ONS-5010/LYTENAVA for use in wet AMD.
At subsequent Type A meetings with the FDA, we learned that the FDA requires the successful completion of an additional adequate and well-controlled clinical trial evaluating ONS-5010/LYTENAVA, as well as additional requested CMC data indicated in the CRL to approve ONS-5010/LYTENAVA for use in wet AMD.
For example, in May 2022, we voluntarily withdrew our BLA to provide additional information requested by the FDA. We re-submitted the BLA to the FDA for ONS-5010/LYTENAVA on August 30, 2022.
For example, in May 2022, we voluntarily withdrew our BLA to provide additional information requested by the FDA. We re-submitted the BLA to the FDA for ONS-5010/LYTENAVA on August 30, 2022.
On August 29, 2023, we received a CRL in which the FDA concluded it could not approve the BLA during this review cycle due to several CMC issues, open observations from pre-approval manufacturing inspections, and a lack of substantial evidence.
On August 29, 2023, we received a CRL in which the FDA concluded it could not approve the BLA during this review cycle due to several CMC issues, open observations from pre-approval manufacturing inspections, and a lack of substantial evidence.
The commencement and completion of clinical trials can be delayed for a number of reasons, including delays related to: ● the FDA disagreeing as to the design or implementation of our clinical studies; ● obtaining FDA authorizations to commence a trial or reaching a consensus with the FDA on trial design; 40 Table of Contents ● any failure or delay in reaching an agreement with CROs and clinical trial sites, the terms of which can be subject to extensive negotiation and may vary significantly among different CROs and trial sites; ● obtaining approval from one or more IRBs; ● IRBs refusing to approve, suspending or terminating the trial at an investigational site, precluding enrollment of additional subjects, or withdrawing their approval of the trial; ● changes to clinical trial protocol; ● clinical sites deviating from trial protocol or dropping out of a trial; ● manufacturing sufficient quantities of product candidate or obtaining sufficient quantities of combination therapies for use in clinical trials; ● subjects failing to enroll or remain in our trial at the rate we expect, or failing to return for post-treatment follow-up; ● subjects choosing an alternative treatment, or participating in competing clinical trials; ● lack of adequate funding to continue the clinical trial; ● subjects experiencing severe or unexpected drug-related adverse effects; ● occurrence of serious adverse events in trials of the same class of agents conducted by other companies; ● selection of clinical end points that require prolonged periods of clinical observation or analysis of the resulting data; ● a facility manufacturing our product candidates or any of their components being ordered by the FDA to temporarily or permanently shut down due to violations of cGMP, regulations or other applicable requirements, or infections or cross-contaminations of product candidates in the manufacturing process; ● any changes to our manufacturing process that may be necessary or desired; ● third-party clinical investigators losing the licenses or permits necessary to perform our clinical trials, not performing our clinical trials on our anticipated schedule or consistent with the clinical trial protocol, GCP, or other regulatory requirements; ● third-party contractors not performing data collection or analysis in a timely or accurate manner; or ● third-party contractors becoming debarred or suspended or otherwise penalized by the FDA or other government or regulatory authorities for violations of regulatory requirements, in which case we may need to find a substitute contractor, and we may not be able to use some or all of the data produced by such contractors in support of our marketing applications.
The commencement and completion of clinical trials can be delayed for a number of reasons, including delays related to: ● the FDA disagreeing as to the design or implementation of our clinical studies; ● obtaining FDA authorizations to commence a trial or reaching a consensus with the FDA on trial design; ● any failure or delay in reaching an agreement with CROs and clinical trial sites, the terms of which can be subject to extensive negotiation and may vary significantly among different CROs and trial sites; ● obtaining approval from one or more IRBs; ● IRBs refusing to approve, suspending or terminating the trial at an investigational site, precluding enrollment of additional subjects, or withdrawing their approval of the trial; ● changes to clinical trial protocol; ● clinical sites deviating from trial protocol or dropping out of a trial; ● manufacturing sufficient quantities of product candidate or obtaining sufficient quantities of combination therapies for use in clinical trials; ● subjects failing to enroll or remain in our trial at the rate we expect, or failing to return for post-treatment follow-up; ● subjects choosing an alternative treatment, or participating in competing clinical trials; 40 Table of Contents ● lack of adequate funding to continue the clinical trial; ● subjects experiencing severe or unexpected drug-related adverse effects; ● occurrence of serious adverse events in trials of the same class of agents conducted by other companies; ● selection of clinical end points that require prolonged periods of clinical observation or analysis of the resulting data; ● a facility manufacturing our product candidates or any of their components being ordered by the FDA to temporarily or permanently shut down due to violations of cGMP, regulations or other applicable requirements, or infections or cross-contaminations of product candidates in the manufacturing process; ● any changes to our manufacturing process that may be necessary or desired; ● third-party clinical investigators losing the licenses or permits necessary to perform our clinical trials, not performing our clinical trials on our anticipated schedule or consistent with the clinical trial protocol, GCP, or other regulatory requirements; ● third-party contractors not performing data collection or analysis in a timely or accurate manner; or ● third-party contractors becoming debarred or suspended or otherwise penalized by the FDA or other government or regulatory authorities for violations of regulatory requirements, in which case we may need to find a substitute contractor, and we may not be able to use some or all of the data produced by such contractors in support of our marketing applications.
The degree of market acceptance of ONS-5010/LYTENAVA or any of our product candidates, if approved for commercial sale, will depend on a number of factors, including but not limited to: ● the safety and efficacy of the product in clinical trials, and potential advantages over competing treatments; ● the publication of unfavorable safety or efficacy data concerning our product by third-parties; ● the prevalence and severity of any side effects, including any limitations or warnings contained in a product’s approved labeling; ● the clinical indications for which approval is granted; 45 Table of Contents ● recognition and acceptance of our product candidates over our competitors’ products; ● prevalence of the disease or condition for which the product is approved; ● the cost of treatment, particularly in relation to competing treatments; ● the willingness of the target patient population to try our therapies and of physicians to prescribe these therapies; ● the strength of marketing and distribution support and timing of market introduction of competitive products; ● the extent to which the product is approved for inclusion on formularies of hospitals and managed care organizations; ● publicity concerning our products or competing products and treatments; ● the extent to which third-party payors provide coverage and adequate reimbursement for ONS-5010/LYTENAVA, or any other product candidates we may pursue that may be approved; ● our ability to maintain compliance with regulatory requirements; and ● labeling or naming imposed by FDA or other regulatory authorities.
The degree of market acceptance of ONS-5010/LYTENAVA or any of our product candidates, if approved for commercial sale, will depend on a number of factors, including but not limited to: ● the safety and efficacy of the product in clinical trials, and potential advantages over competing treatments; ● the publication of unfavorable safety or efficacy data concerning our product by third-parties; ● the prevalence and severity of any side effects, including any limitations or warnings contained in a product’s approved labeling; ● the clinical indications for which approval is granted; ● recognition and acceptance of our product candidates over our competitors’ products; ● prevalence of the disease or condition for which the product is approved; ● the cost of treatment, particularly in relation to competing treatments; ● the willingness of the target patient population to try our therapies and of physicians to prescribe these therapies; ● the strength of marketing and distribution support and timing of market introduction of competitive products; ● the extent to which the product is approved for inclusion on formularies of hospitals and managed care organizations; ● publicity concerning our products or competing products and treatments; 45 Table of Contents ● the extent to which third-party payors provide coverage and adequate reimbursement for ONS-5010/LYTENAVA, or any other product candidates we may pursue that may be approved; ● our ability to maintain compliance with regulatory requirements; and ● labeling or naming imposed by FDA or other regulatory authorities.
Our development efforts may fail to yield additional product candidates suitable for clinical development and commercialization for a number of reasons, including but not limited to the following: ● we may not be successful in identifying potential product candidates that pass our strict screening criteria; 63 Table of Contents ● we may not be able to overcome technological hurdles to development or a product candidate may not be capable of producing commercial quantities at an acceptable cost, or at all; ● we may not be able to assemble sufficient resources to acquire or discover additional product candidates; ● our product candidates may not succeed in preclinical or clinical testing; ● competitors may develop alternatives that render our product candidates obsolete or less attractive or the market for a product candidate may change such that a product candidate may not justify further development.
Our development efforts may fail to yield additional product candidates suitable for clinical development and commercialization for a number of reasons, including but not limited to the following: ● we may not be successful in identifying potential product candidates that pass our strict screening criteria; ● we may not be able to overcome technological hurdles to development or a product candidate may not be capable of producing commercial quantities at an acceptable cost, or at all; ● we may not be able to assemble sufficient resources to acquire or discover additional product candidates; 63 Table of Contents ● our product candidates may not succeed in preclinical or clinical testing; ● competitors may develop alternatives that render our product candidates obsolete or less attractive or the market for a product candidate may change such that a product candidate may not justify further development.
If we are unable to maintain favorable pricing and reimbursement status in EU Member States for product candidates that we may successfully develop and for which we may obtain regulatory approval, any anticipated revenue from and growth prospects for those products in the EU could be negatively affected. ​ In addition, on April 26, 2023, the European Commission adopted a proposal for a new Directive and Regulation to revise the existing pharmaceutical legislation and on 10 April 2024, the Parliament adopted its related position.
If we are unable to maintain favorable pricing and reimbursement status in EU Member States for product candidates that we may successfully develop and for which we may obtain regulatory approval, any anticipated revenue from and growth prospects for those products in the EU could be negatively affected. ​ In addition, on April 26, 2023, the European Commission adopted a proposal for a new Directive and Regulation to revise the existing pharmaceutical legislation and on April 10, 2024, the Parliament adopted its related position.
Our amended and restated certificate of incorporation, as amended, amended and restated bylaws, as amended and Delaware law contain provisions that may have the effect of delaying or preventing a change in control of us or changes in our management.
Our amended and restated certificate of incorporation, as amended, amended and restated bylaws and Delaware law contain provisions that may have the effect of delaying or preventing a change in control of us or changes in our management.
Our charter documents also contain other provisions that could have an anti-takeover effect, such as: ● establishing a classified board of directors so that not all members of our board of directors are elected at one time; 81 Table of Contents ● permitting the board of directors to establish the number of directors and fill any vacancies and newly created directorships; ● providing that directors may only be removed for cause; ● prohibiting cumulative voting for directors; ● requiring super-majority voting to amend some provisions in our amended and restated certificate of incorporation and amended and restated bylaws; ● authorizing the issuance of “blank check” preferred stock that our board of directors could use to implement a stockholder rights plan; ● eliminating the ability of stockholders to call special meetings of stockholders; and ● prohibiting stockholder action by written consent, which requires all stockholder actions to be taken at a meeting of our stockholders.
Our charter documents also contain other provisions that could have an anti-takeover effect, such as: ● establishing a classified board of directors so that not all members of our board of directors are elected at one time; ● permitting the board of directors to establish the number of directors and fill any vacancies and newly created directorships; ● providing that directors may only be removed for cause; ● prohibiting cumulative voting for directors; ● requiring super-majority voting to amend some provisions in our amended and restated certificate of incorporation and amended and restated bylaws; 81 Table of Contents ● authorizing the issuance of “blank check” preferred stock that our board of directors could use to implement a stockholder rights plan; ● eliminating the ability of stockholders to call special meetings of stockholders; and ● prohibiting stockholder action by written consent, which requires all stockholder actions to be taken at a meeting of our stockholders.
The market price of our securities could be subject to wide fluctuations in response to a variety of factors, including but not limited to: ● the success of competitive services, products or technologies; ● adverse results or delays in preclinical or clinical trials; ● any inability to obtain additional funding; ● any delay in filing an IND, BLA or other regulatory submission for ONS-5010/LYTENAVA, or any of our product candidates when planned, and any adverse development or perceived adverse development with respect to the applicable regulatory agency’s review of that IND, BLA or other regulatory submission; ● the perception of limited market sizes or pricing for ONS-5010/LYTENAVA or any of our other product candidates; ● failure to successfully develop and commercialize ONS-5010/LYTENAVA or any of our other product candidates; ● post-marketing safety issues relating to our product candidates generally; ● failure to maintain our existing strategic collaborations or enter into new collaborations; ● failure by us or our licensors and strategic collaboration partners to prosecute, maintain or enforce our intellectual property rights; ● changes in laws or regulations applicable to our products; ● any inability to obtain adequate product supply for our product candidates or the inability to do so at acceptable prices; ● adverse regulatory decisions; ● introduction of new products, services or technologies by our competitors; ● failure to meet or exceed financial projections we may provide to the public; ● failure to meet or exceed the financial projections of the investment community; ● the perception of the pharmaceutical industry by the public, legislatures, regulators and the investment community; 76 Table of Contents ● announcements of significant acquisitions, strategic partnerships, joint ventures or capital commitments by us, our strategic collaboration partners or our competitors; ● disputes or other developments relating to proprietary rights, including patents, litigation matters and our ability to obtain patent protection for our technologies; ● additions or departures of key scientific or management personnel; ● significant lawsuits, including stockholder litigation and litigation filed by us or filed against us pertaining to patent infringement or other violations of intellectual property rights; ● the outcomes of any citizens petitions filed by parties seeking to restrict or limit the approval of ONS-5010/LYTENAVA in the EU or UK, or any of our product candidates that may be approved; ● if securities or industry analysts do not publish research or reports about our business or if they issue an adverse or misleading opinion regarding our stock; ● changes in the market valuations of similar companies; ● general economic, industry or market conditions; ● sales of our securities by us or our stockholders in the future; ● trading volume of our securities; ● issuance of patents to third parties that could prevent our ability to commercialize our product candidates; ● the loss of one or more employees constituting our leadership team; ● changes in regulatory requirements that could make it more difficult for us to develop our product candidates; and ● the other factors described in this “Risk Factors” section.
The market price of our securities could be subject to wide fluctuations in response to a variety of factors, including but not limited to: ● the success of competitive services, products or technologies; ● adverse results or delays in preclinical or clinical trials; 75 Table of Contents ● any inability to obtain additional funding; ● any delay in filing an IND, BLA or other regulatory submission for ONS-5010/LYTENAVA, or any of our product candidates when planned, and any adverse development or perceived adverse development with respect to the applicable regulatory agency’s review of that IND, BLA or other regulatory submission; ● the perception of limited market sizes or pricing for ONS-5010/LYTENAVA or any of our other product candidates; ● failure to successfully develop and commercialize ONS-5010/LYTENAVA or any of our other product candidates; ● post-marketing safety issues relating to our product candidates generally; ● failure to maintain our existing strategic collaborations or enter into new collaborations; ● failure by us or our licensors and strategic collaboration partners to prosecute, maintain or enforce our intellectual property rights; ● changes in laws or regulations applicable to our products; ● any inability to obtain adequate product supply for our product candidates or the inability to do so at acceptable prices; ● adverse regulatory decisions; ● introduction of new products, services or technologies by our competitors; ● failure to meet or exceed financial projections we may provide to the public; ● failure to meet or exceed the financial projections of the investment community; ● the perception of the pharmaceutical industry by the public, legislatures, regulators and the investment community; ● announcements of significant acquisitions, strategic partnerships, joint ventures or capital commitments by us, our strategic collaboration partners or our competitors; ● disputes or other developments relating to proprietary rights, including patents, litigation matters and our ability to obtain patent protection for our technologies; ● additions or departures of key scientific or management personnel; ● significant lawsuits, including stockholder litigation and litigation filed by us or filed against us pertaining to patent infringement or other violations of intellectual property rights; ● the outcomes of any citizens petitions filed by parties seeking to restrict or limit the approval of ONS-5010/LYTENAVA in the EU or UK, or any of our product candidates that may be approved; ● if securities or industry analysts do not publish research or reports about our business or if they issue an adverse or misleading opinion regarding our stock; 76 Table of Contents ● changes in the market valuations of similar companies; ● general economic, industry or market conditions; ● sales of our securities by us or our stockholders in the future; ● trading volume of our securities; ● issuance of patents to third parties that could prevent our ability to commercialize our product candidates; ● the loss of one or more employees constituting our leadership team; ● changes in regulatory requirements that could make it more difficult for us to develop our product candidates; and ● the other factors described in this “Risk Factors” section.
We anticipate that our expenses may increase substantially if and as we: ● prepare to launch and market ONS-5010/LYTENAVA in the EU and UK, and in other countries if the product is approved in these territories; ● continue the clinical development of ONS-5010/LYTENAVA; ● advance ONS-5010/LYTENAVA into additional clinical trials; ● change or add contract manufacturing providers, clinical research service providers, testing laboratories, device suppliers, legal service providers or other vendors or suppliers; ● seek regulatory and marketing approvals for ONS-5010/LYTENAVA in the United States and other markets if we successfully complete clinical trials; 27 Table of Contents ● establish a sales, marketing and distribution infrastructure to commercialize any products for which we may obtain marketing approval and for which we retain such rights; ● seek to identify, assess, acquire or develop other product candidates that may be complementary to ONS-5010/LYTENAVA; ● make upfront, milestone, royalty or other payments under any license agreements; ● seek to create, maintain, protect and expand our intellectual property portfolio; ● engage in litigation, including the pending securities class action lawsuit, as well as any other potential litigation; ● seek to attract and retain skilled personnel; ● create additional infrastructure to support our operations as a public company and any future commercialization efforts; and ● experience any delays or encounter issues with any of the above, including but not limited to failed clinical trials, conflicting results, safety issues or regulatory challenges that may require longer follow-up of existing studies, additional major studies or additional supportive studies in order to pursue marketing approval.
We anticipate that our expenses may increase substantially if and as we: ● continue our product launch and market ONS-5010/LYTENAVA in the EU and UK, and in other countries if the product is approved in these territories; ● continue the clinical development of ONS-5010/LYTENAVA; ● advance ONS-5010/LYTENAVA into additional clinical trials; ● change or add contract manufacturing providers, clinical research service providers, testing laboratories, device suppliers, legal service providers or other vendors or suppliers; ● seek regulatory and marketing approvals for ONS-5010/LYTENAVA in the United States and other markets if we successfully complete clinical trials; ● establish a sales, marketing and distribution infrastructure to commercialize any products for which we may obtain marketing approval and for which we retain such rights; ● seek to identify, assess, acquire or develop other product candidates that may be complementary to ONS-5010/LYTENAVA; ● make upfront, milestone, royalty or other payments under any license agreements; ● seek to create, maintain, protect and expand our intellectual property portfolio; ● engage in litigation, including the pending securities class action lawsuit, as well as any other pending or potential litigation; ● seek to attract and retain skilled personnel; 27 Table of Contents ● create additional infrastructure to support our operations as a public company and any future commercialization efforts; and ● experience any delays or encounter issues with any of the above, including but not limited to failed clinical trials, conflicting results, safety issues or regulatory challenges that may require longer follow-up of existing studies, additional major studies or additional supportive studies in order to pursue marketing approval.
Events that may prevent successful or timely completion of clinical development include but are not limited to: ● inability to generate sufficient preclinical, toxicology or other in vivo or in vitro data to support the initiation of human clinical trials; ● delays in reaching a consensus with regulatory authorities on study design; ● delays in reaching agreement on acceptable terms with prospective contract research organizations, or CROs, and clinical trial sites, the terms of which can be subject to extensive negotiation and may vary significantly among different CROs and clinical trial sites; ● delays in obtaining required IRB approval at each clinical trial site, or positive Ethics Committees opinions; ● imposition of a clinical hold by regulatory authorities, after review of an IND, application or amendment or equivalent filing, or an inspection of our clinical trial operations or trial sites, or as a result of adverse events reported during a clinical trial; ● further delays in recruiting suitable patients to participate in our clinical trials; ● difficulty collaborating with patient groups and investigators; ● failure by our CROs, other third parties or us to adhere to clinical trial requirements; ● failure to perform in accordance with the FDA’s good clinical practice, or GCP, requirements or applicable regulatory guidelines in other countries; ● delays in having subjects complete participation in a study or return for post-treatment follow-up, or subjects dropping out of a study; ● occurrence of adverse events associated with the product candidate that are viewed to outweigh its potential benefits; ● changes in regulatory requirements and guidance that require amending or submitting new clinical protocols; ● the cost of clinical trials of our product candidates being greater than we anticipate; 34 Table of Contents ● clinical trials of our product candidates producing negative or inconclusive results, which may result in us deciding or regulators requiring us to conduct additional clinical trials or abandon product development programs; and ● delays in manufacturing, testing, releasing, validating or importing/exporting and/or distributing sufficient stable quantities of our product candidates for use in clinical trials or the inability to do any of the foregoing.
Events that may prevent successful or timely completion of clinical development include but are not limited to: ● inability to generate sufficient preclinical, toxicology or other in vivo or in vitro data to support the initiation of human clinical trials; ● delays in reaching a consensus with regulatory authorities on study design; ● delays in reaching agreement on acceptable terms with prospective contract research organizations, or CROs, and clinical trial sites, the terms of which can be subject to extensive negotiation and may vary significantly among different CROs and clinical trial sites; ● delays in obtaining required IRB approval at each clinical trial site, or positive Ethics Committees opinions; 33 Table of Contents ● imposition of a clinical hold by regulatory authorities, after review of an IND, application or amendment or equivalent filing, or an inspection of our clinical trial operations or trial sites, or as a result of adverse events reported during a clinical trial; ● further delays in recruiting suitable patients to participate in our clinical trials; ● difficulty collaborating with patient groups and investigators; ● failure by our CROs, other third parties or us to adhere to clinical trial requirements; ● failure to perform in accordance with the FDA’s good clinical practice, or GCP, requirements or applicable regulatory guidelines in other countries; ● delays in having subjects complete participation in a study or return for post-treatment follow-up, or subjects dropping out of a study; ● occurrence of adverse events associated with the product candidate that are viewed to outweigh its potential benefits; ● changes in regulatory requirements and guidance that require amending or submitting new clinical protocols; ● the cost of clinical trials of our product candidates being greater than we anticipate; ● clinical trials of our product candidates producing negative or inconclusive results, which may result in us deciding or regulators requiring us to conduct additional clinical trials or abandon product development programs; and ● delays in manufacturing, testing, releasing, validating or importing/exporting and/or distributing sufficient stable quantities of our product candidates for use in clinical trials or the inability to do any of the foregoing.
The healthcare laws that may affect our ability to operate include but are not limited to: ● the federal Anti-Kickback Statute, which prohibits, among other things, persons and entities from knowingly and willfully soliciting, receiving, offering or paying remuneration, directly or indirectly, in cash or in kind, to induce, reward, or in return for either the referral of an individual for, or the purchase, recommendation, order or furnishing of an item or service reimbursable, in whole or in part, under a federal healthcare program, such as the Medicare and Medicaid programs; ● federal civil and criminal false claims laws and civil monetary penalty laws, including the civil False Claims Act, which can be enforced by private individuals through civil whistleblower or qui tam actions, which prohibit, among other things, individuals or entities from knowingly presenting or causing to be presented claims for payment from Medicare, Medicaid or other government health programs that are false or fraudulent; ● HIPAA, which created additional federal criminal statutes that prohibit, among other things, executing a scheme to defraud any healthcare benefit program and making false statements relating to healthcare matters; ● HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act, and their implementing regulations, which imposes certain requirements, including mandatory contractual terms, relating to the privacy, security and transmission of individually identifiable health information on health plans, certain healthcare providers, and healthcare clearinghouses, known as covered entities, and their business associates that provide services to the covered entity that involve individually identifiable health information and their subcontractors that use, disclose or otherwise process individually identifiable health information; ● the federal legislation commonly referred to as the Physician Payments Sunshine Act under the Affordable Care Act, which requires certain manufacturers of drugs, devices, biologics and medical supplies for which payment is available under Medicare, Medicaid, or the Children’s Health Insurance Program, with specific exceptions, to report annually to the Centers for Medicare & Medicaid Services information related to payments and other transfers of value made by such manufacturers to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors), certain other healthcare providers (such as physicians assistants and nurse practitioners), and teaching hospitals, as well as ownership and investment interests held by physicians and their immediate family members; and ● analogous state and foreign laws and regulations, such as anti-kickback and false claims laws that may apply to items or services reimbursed by any third-party payor, including commercial insurers; state and foreign laws that require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the government or otherwise restrict payments that may be made to healthcare providers and other potential referral sources; state and foreign laws that require drug manufacturers to report information related to payments and other transfers of value to physicians and other healthcare providers or marketing expenditures or drug pricing; state, foreign and local laws that require the registration of pharmaceutical sales representatives; and state and foreign laws governing the privacy and security of health information in certain circumstances, many of which differ from each other in significant ways and may not have the same effect, thus complicating compliance efforts.
The healthcare laws that may affect our ability to operate include but are not limited to: ● the federal Anti-Kickback Statute, which prohibits, among other things, persons and entities from knowingly and willfully soliciting, receiving, offering or paying remuneration, directly or indirectly, in cash or in kind, to induce, reward, or in return for either the referral of an individual for, or the purchase, recommendation, order or furnishing of an item or service reimbursable, in whole or in part, under a federal healthcare program, such as the Medicare and Medicaid programs; ● federal civil and criminal false claims laws and civil monetary penalty laws, including the civil False Claims Act, which can be enforced by private individuals through civil whistleblower or qui tam actions, which prohibit, among other things, individuals or entities from knowingly presenting or causing to be presented claims for payment from Medicare, Medicaid or other government health programs that are false or fraudulent; 67 Table of Contents ● HIPAA, which created additional federal criminal statutes that prohibit covered entities and business associates from, among other things, executing a scheme to defraud any healthcare benefit program and making false statements relating to healthcare matters; ● HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act, and their implementing regulations, which imposes certain requirements, including mandatory contractual terms, relating to the privacy, security and transmission of individually identifiable health information on health plans, certain healthcare providers, and healthcare clearinghouses, known as covered entities, and their business associates that provide services to the covered entity that involve individually identifiable health information and their subcontractors that use, disclose or otherwise process individually identifiable health information; ● the federal legislation commonly referred to as the Physician Payments Sunshine Act under the Affordable Care Act, which requires certain manufacturers of drugs, devices, biologics and medical supplies for which payment is available under Medicare, Medicaid, or the Children’s Health Insurance Program, with specific exceptions, to report annually to the Centers for Medicare & Medicaid Services information related to payments and other transfers of value made by such manufacturers to physicians (defined to include doctors, dentists, optometrists, podiatrists and chiropractors), certain other healthcare providers (such as physicians assistants and nurse practitioners), and teaching hospitals, as well as ownership and investment interests held by physicians and their immediate family members; and ● analogous state and foreign laws and regulations, such as anti-kickback and false claims laws that may apply to items or services reimbursed by any third-party payor, including commercial insurers; state and foreign laws that require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the government or otherwise restrict payments that may be made to healthcare providers and other potential referral sources; state and foreign laws that require drug manufacturers to report information related to payments and other transfers of value to physicians and other healthcare providers or marketing expenditures or drug pricing; state, foreign and local laws that require the registration of pharmaceutical sales representatives; and state and foreign laws governing the privacy and security of health information in certain circumstances, many of which differ from each other in significant ways and may not have the same effect, thus complicating compliance efforts.
We have also entered into a strategic relationship with Cencora in preparation for the anticipated commercial launch of ONS-5010/LYTENAVA in the EEA, UK, and in the United States, if approved by the FDA, pursuant to which Cencora would provide comprehensive launch support in the EEA and the UK including pharmacovigilance, regulatory affairs, quality management, market access support, importation, field solutions, third-party logistics services and distribution, andmedical information, as well as other regions outside the United States.
We have also entered into a strategic relationship with Cencora for our commercial launch of ONS-5010/LYTENAVA in the EEA, UK, and in preparation for the anticipated commercial launch in the United States, if approved by the FDA, pursuant to which Cencora would provide comprehensive launch support in the EEA and the UK including pharmacovigilance, regulatory affairs, quality management, market access support, importation, field solutions, third-party logistics services and distribution, andmedical information, as well as other regions outside the United States.
The FDA could delay, limit or deny approval of a product candidate for many reasons, or request additional information, including because they: ● may not deem our product candidate to be adequately safe and effective; ● may not agree that the data collected from clinical trials are acceptable or sufficient to support the submission of a BLA or other submission or to obtain regulatory approval, and may impose requirements for additional preclinical studies or clinical trials; ● may determine that adverse events experienced by participants in our clinical trials represents an unacceptable level of risk; ● may determine that population studied in the clinical trial may not be sufficiently broad or representative to assure safety in the full population for which we seek approval; ● may not accept clinical data from trials which are conducted at clinical facilities or in countries where the standard of care is potentially different from that of the United States; ● may disagree regarding the formulation, labeling and/or the specifications; ● may not approve the manufacturing processes or facilities associated with our product candidate; ● may change approval policies or adopt new regulations; or 39 Table of Contents ● may not accept a submission due to, among other reasons, the content or formatting of the submission.
The FDA could delay, limit or deny approval of a product candidate for many reasons, or request additional information, including because they: ● may not deem our product candidate to be adequately safe and effective; 38 Table of Contents ● may not agree that the data collected from clinical trials are acceptable or sufficient to support the submission of a BLA or other submission or to obtain regulatory approval, and may impose requirements for additional preclinical studies or clinical trials; ● may determine that adverse events experienced by participants in our clinical trials represents an unacceptable level of risk; ● may determine that population studied in the clinical trial may not be sufficiently broad or representative to assure safety in the full population for which we seek approval; ● may not accept clinical data from trials which are conducted at clinical facilities or in countries where the standard of care is potentially different from that of the United States; ● may disagree regarding the formulation, labeling and/or the specifications; ● may not approve the manufacturing processes or facilities associated with our product candidate; ● may change approval policies or adopt new regulations; or ● may not accept a submission due to, among other reasons, the content or formatting of the submission.
Obtaining approval from the FDA or similar regulatory approval is an extensive, lengthy, expensive and inherently uncertain process, and the FDA or other foreign regulatory authorities may delay, limit or deny approval of ONS-5010/LYTENAVA for many reasons, including: ● we may not be able to demonstrate that ONS-5010/LYTENAVA is effective as a treatment for any of our currently targeted indications to the satisfaction of the FDA or other relevant regulatory authorities; ● the relevant regulatory authorities may require additional pre-approval studies or clinical trials, which would increase our costs and prolong our development timelines; ● the results of our clinical trials may not meet the level of statistical or clinical significance required by the FDA or other relevant regulatory authorities for marketing approval; ● the FDA or other relevant regulatory authorities may disagree with the number, design, size, conduct or implementation of our clinical trials; ● the FDA or other relevant regulatory authorities may not find the data from nonclinical studies or clinical trials sufficient to demonstrate that the clinical and other benefits of these products outweigh their safety risks; 32 Table of Contents ● the FDA or other relevant regulatory authorities may disagree with our interpretation of data or significance of results from the nonclinical studies and clinical trials of ONS-5010/LYTENAVA and any future product candidate, or may require that we conduct additional trials; ● the FDA or other relevant regulatory authorities may require development of a risk evaluation and mitigation strategy, or REMS, or its equivalent, as a condition of approval; ● the FDA or other relevant regulatory authorities may require additional post-marketing studies, which would be costly; ● the FDA or other relevant regulatory authorities may identify deficiencies in the manufacturing processes or facilities of our third-party manufacturers; or ● the FDA or other relevant regulatory authorities may change their approval policies or adopt new regulations.
Obtaining approval from the FDA or similar regulatory approval is an extensive, lengthy, expensive and inherently uncertain process, and the FDA or other foreign regulatory authorities may delay, limit or deny approval of ONS-5010/LYTENAVA for many reasons, including: ● we may not be able to demonstrate that ONS-5010/LYTENAVA is effective as a treatment for any of our currently targeted indications to the satisfaction of the FDA or other relevant regulatory authorities; ● the relevant regulatory authorities may require additional pre-approval studies or clinical trials, which would increase our costs and prolong our development timelines; ● the results of our clinical trials may not meet the level of statistical or clinical significance required by the FDA or other relevant regulatory authorities for marketing approval; ● the FDA or other relevant regulatory authorities may disagree with the number, design, size, conduct or implementation of our clinical trials; ● the FDA or other relevant regulatory authorities may not find the data from nonclinical studies or clinical trials sufficient to demonstrate that the clinical and other benefits of these products outweigh their safety risks; ● the FDA or other relevant regulatory authorities may disagree with our interpretation of data or significance of results from the nonclinical studies and clinical trials of ONS-5010/LYTENAVA and any future product candidate, or may require that we conduct additional trials; ● the FDA or other relevant regulatory authorities may require development of a risk evaluation and mitigation strategy, or REMS, or its equivalent, as a condition of approval; ● the FDA or other relevant regulatory authorities may require additional post-marketing studies, which would be costly; ● the FDA or other relevant regulatory authorities may identify deficiencies in the manufacturing processes or facilities of our third-party manufacturers; or ● the FDA or other relevant regulatory authorities may change their approval policies or adopt new regulations.
In addition, if, following the marketing authorizations of ONS-5010/LYTENAVA in the EU and UK, or if ONS-5010/LYTENAVA receives FDA approval, or if any future product candidate receives marketing approval, and we or others later identify undesirable side effects, a number of potentially significant negative consequences could result, including: ● regulatory authorities may withdraw, suspend, or vary approval of such product; ● we may be required to recall a product or change the way such product is administered to patients; ● regulatory authorities may require additional warnings on the label, such as a “black box” warning or a contraindication, or issue safety alerts, Dear Healthcare Provider letters, press releases or other communications containing warnings or other safety information about the product; ● we may be required to implement a REMS, or create a medication guide outlining the risks of such side effects for distribution to patients, or comparable foreign strategies; ● additional restrictions may be imposed on the marketing or promotion of the particular product or the manufacturing processes for the product or any component thereof; ● we could be sued and held liable for harm caused to patients; 43 Table of Contents ● such product could become less competitive; and ● our reputation may suffer.
In addition, if, following the marketing authorizations of ONS-5010/LYTENAVA in the EU and UK, or if ONS-5010/LYTENAVA receives FDA approval, or if any future product candidate receives marketing approval, and we or others later identify undesirable side effects, a number of potentially significant negative consequences could result, including: ● regulatory authorities may withdraw, suspend, or vary approval of such product; ● we may be required to recall a product or change the way such product is administered to patients; ● regulatory authorities may require additional warnings on the label, such as a “black box” warning or a contraindication, or issue safety alerts, Dear Healthcare Provider letters, press releases or other communications containing warnings or other safety information about the product; ● we may be required to implement a REMS, or create a medication guide outlining the risks of such side effects for distribution to patients, or comparable foreign strategies; ● additional restrictions may be imposed on the marketing or promotion of the particular product or the manufacturing processes for the product or any component thereof; ● we could be sued and held liable for harm caused to patients; ● such product could become less competitive; and ● our reputation may suffer.
Patient enrollment is also affected by other factors, including: ● severity of the disease under investigation; ● our ability to recruit clinical trial investigators of appropriate competencies and experience; ● invasive procedures required to obtain evidence of the product candidate’s performance during the clinical trial; ● availability and efficacy of approved medications for the disease under investigation; ● eligibility criteria defined in the protocol for the trial in question; ● the size of the patient population required for analysis of the trial’s primary endpoints; ● perceived risks and benefits; ● efforts to facilitate timely enrollment in clinical trials; ● reluctance of physicians to encourage patient participation in clinical trials; ● the ability to monitor patients adequately during and after treatment; ● our ability to obtain and maintain patient consents; and ● proximity and availability of clinical trial sites for prospective patients.
Patient enrollment is also affected by other factors, including: ● severity of the disease under investigation; 41 Table of Contents ● our ability to recruit clinical trial investigators of appropriate competencies and experience; ● invasive procedures required to obtain evidence of the product candidate’s performance during the clinical trial; ● availability and efficacy of approved medications for the disease under investigation; ● eligibility criteria defined in the protocol for the trial in question; ● the size of the patient population required for analysis of the trial’s primary endpoints; ● perceived risks and benefits; ● efforts to facilitate timely enrollment in clinical trials; ● reluctance of physicians to encourage patient participation in clinical trials; ● the ability to monitor patients adequately during and after treatment; ● our ability to obtain and maintain patient consents; and ● proximity and availability of clinical trial sites for prospective patients.
The process of manufacturing our ONS-5010/LYTENAVA and our other monoclonal antibody product candidates is complex, highly regulated and subject to several risks, including but not limited to: ● failure to establish contracts with CMOs, and device vendors where applicable; ● product loss due to contamination, equipment failure or improper installation or operation of equipment or vendor or operator error; ● infringing intellectual property rights of third parties relating to manufacturing and quality testing; ● failure to achieve or maintain compliance with MHRA, EEA authorities’ or FDA’s requirements for acceptance of the applicable manufacturing facilities; and 52 Table of Contents ● labor shortages, natural disasters and power failures.
The process of manufacturing our ONS-5010/LYTENAVA and our other monoclonal antibody product candidates is complex, highly regulated and subject to several risks, including but not limited to: ● failure to establish contracts with CMOs, and device vendors where applicable; ● product loss due to contamination, equipment failure or improper installation or operation of equipment or vendor or operator error; ● infringing intellectual property rights of third parties relating to manufacturing and quality testing; ● failure to achieve or maintain compliance with MHRA, EEA authorities’ or FDA’s requirements for acceptance of the applicable manufacturing facilities; and ● labor shortages, natural disasters and power failures.
These lawsuits, and any other lawsuits to which we are subject, will be costly to defend or pursue and are uncertain in its outcome”, we and two of our officers have been named as defendants a class action lawsuit filed in the United States District Court for the District of New Jersey and certain of our officers and directors were named as defendants in a shareholder derivative action filed in the District Court of the District of Delaware.
These lawsuits, and any other lawsuits to which we are subject, will be costly to defend or pursue and are uncertain in its outcome”, we and two of our current and former officers have been named as defendants a class action lawsuit filed in the United States District Court for the District of New Jersey and certain of our current and former officers and directors were named as defendants in a shareholder derivative action filed in the District Court of the District of Delaware.
For example, under the GDPR, in the event of any non-compliance, companies subject to the laws 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, in each case, 4% of annual global revenue, whichever is greater; or private litigation related to processing of personal data brought by classes of data subjects or consumer protection organizations authorized at law to represent their interests.
For example, under the GDPR, in the event of any non-compliance, companies subject to the laws 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, in each case, 4% of annual global revenue, whichever is greater; or private 72 Table of Contents litigation related to processing of personal data brought by classes of data subjects or consumer protection organizations authorized at law to represent their interests.
If we fail to comply with applicable regulatory requirements, a regulatory authority or enforcement authority may, among other things: ​ ● issue untitled and warning letters; ● impose civil or criminal penalties; ● suspend, vary or withdraw regulatory approval; ● suspend any of our ongoing clinical trials; ● refuse to approve pending applications or supplements to approved applications submitted by us; ● total or partial suspension of production, distribution or manufacturing; ● impose restrictions on our operations, including closing our manufacturing facilities; ● suspension of licenses; or ● seize or detain products or require a product recall.
If we fail to comply with applicable regulatory requirements, a regulatory authority or enforcement authority may, among other things: ​ ● issue untitled and warning letters; ● impose civil or criminal penalties; ● suspend, vary or withdraw regulatory approval; 37 Table of Contents ● suspend any of our ongoing clinical trials; ● refuse to approve pending applications or supplements to approved applications submitted by us; ● total or partial suspension of production, distribution or manufacturing; ● impose restrictions on our operations, including closing our manufacturing facilities; ● suspension of licenses; or ● seize or detain products or require a product recall.
Enrollment delays in our clinical trials may result in increased development costs, which would cause the value of our company to decline and limit our ability to obtain additional financing. ​ 42 Table of Contents Adverse side effects or other safety risks associated with ONS-5010/LYTENAVA or any future product candidate could delay or preclude approval, cause us to suspend or discontinue clinical trials, abandon further development, limit the commercial profile of an approved label, or result in significant negative consequences following marketing approval, if any.
Enrollment delays in our clinical trials may result in increased development costs, which would cause the value of our company to decline and limit our ability to obtain additional financing. ​ Adverse side effects or other safety risks associated with ONS-5010/LYTENAVA or any future product candidate could delay or preclude approval, cause us to suspend or discontinue clinical trials, abandon further development, limit the commercial profile of an approved label, or result in significant negative consequences following marketing approval, if any.
Certain of our officers and directors have also been named as defendants in a pending shareholder derivative action. These lawsuits, and potential similar or related lawsuits, could result in substantial damages, divert management’s time and attention from our business, and have a material adverse effect on our results of operations.
Certain of our current and former officers and directors have also been named as defendants in a pending shareholder derivative action. These lawsuits, and potential similar or related lawsuits, could result in substantial damages, divert management’s time and attention from our business, and have a material adverse effect on our results of operations.
In addition, the combinations will likely not have been previously tested and may, among other things, fail to demonstrate synergistic activity, may fail to achieve superior outcomes relative to the use of single agents or other combination therapies, may exacerbate adverse events associated with one of our product candidates when used as monotherapy or may fail to demonstrate sufficient safety or efficacy traits in clinical trials to enable us to complete those clinical trials or obtain marketing approval for the combination therapy.
In addition, the combinations will likely not have been previously tested and may, among other 70 Table of Contents things, fail to demonstrate synergistic activity, may fail to achieve superior outcomes relative to the use of single agents or other combination therapies, may exacerbate adverse events associated with one of our product candidates when used as monotherapy or may fail to demonstrate sufficient safety or efficacy traits in clinical trials to enable us to complete those clinical trials or obtain marketing approval for the combination therapy.
Advertising and promotion of any product candidate that obtains approval in the United States will be heavily scrutinized by the FDA, the U.S. Federal Trade Commission, the Department of Justice, or the DOJ, the Office of Inspector General of the U.S. Department of Health and Human Services, or HHS, state attorneys general, members of the U.S. Congress, and the public.
Advertising and promotion of any product candidate that obtains approval in the United States will be heavily scrutinized by the FDA, the United States Federal Trade Commission, the Department of Justice, or the DOJ, the Office of Inspector General of the United States Department of Health and Human Services, or HHS, state attorneys general, members of the United States Congress, and the public.
If we are not able to comply with the requirements of Section 404 in a timely manner or if we identify or our independent registered public accounting firm identifies deficiencies in our internal control over financial reporting that are deemed to be material weaknesses, the market price of our stock 79 Table of Contents could decline and we could be subject to sanctions or investigations by Nasdaq, the SEC or other regulatory authorities, which would require additional financial and management resources.
If we are not able to comply with the requirements of Section 404 in a timely manner or if we identify or our independent registered public accounting firm identifies deficiencies in our internal control over financial reporting that are deemed to be material weaknesses, the market price of our stock could decline and we could be subject to sanctions or investigations by Nasdaq, the SEC or other regulatory authorities, which would require additional financial and management resources.
Such authorities may impose such a suspension or termination due to a number of factors, including failure to conduct the clinical trial in accordance with regulatory requirements or our clinical protocols, inspection of the clinical trial operations 41 Table of Contents or trial site by the FDA or comparable foreign regulatory authorities resulting in the imposition of a clinical hold, unforeseen safety issues or adverse side effects, failure to demonstrate a benefit from using a pharmaceutical, changes in governmental regulations or administrative actions or lack of adequate funding to continue the clinical trial.
Such authorities may impose such a suspension or termination due to a number of factors, including failure to conduct the clinical trial in accordance with regulatory requirements or our clinical protocols, inspection of the clinical trial operations or trial site by the FDA or comparable foreign regulatory authorities resulting in the imposition of a clinical hold, unforeseen safety issues or adverse side effects, failure to demonstrate a benefit from using a pharmaceutical, changes in governmental regulations or administrative actions or lack of adequate funding to continue the clinical trial.
Our failure or the failure of our third-party manufacturers to comply with applicable regulations could result in sanctions being imposed on us, including fines, injunctions, civil penalties, delays, suspension, variation or withdrawal of approvals, license revocation, seizures or recalls of products, operating restrictions and criminal prosecutions, any of which could adversely affect supplies of ONS-5010/LYTENAVA or any other product candidates that we may develop.
Our failure or the failure of our third-party manufacturers to comply with applicable regulations could result in 51 Table of Contents sanctions being imposed on us, including fines, injunctions, civil penalties, delays, suspension, variation or withdrawal of approvals, license revocation, seizures or recalls of products, operating restrictions and criminal prosecutions, any of which could adversely affect supplies of ONS-5010/LYTENAVA or any other product candidates that we may develop.
Additionally, we do not currently maintain “key person” life insurance on the lives of our executives or any of our employees. 64 Table of Contents We and certain of our officers have been named as defendants in a pending securities class action lawsuit.
Additionally, we do not currently maintain “key person” life insurance on the lives of our executives or any of our employees. 64 Table of Contents We and certain of our current and former officers have been named as defendants in a pending securities class action lawsuit.
Our ability to enjoy any competitive advantages afforded by our own intellectual property depends in large part on our ability to obtain and maintain patents and other intellectual property protection in the United States and in other countries with respect to various proprietary elements of our product candidates, such as, for example, our product formulations and processes for manufacturing our products and our ability to maintain and control the confidentiality of our trade secrets and confidential information critical to our business.
Our ability to enjoy 57 Table of Contents any competitive advantages afforded by our own intellectual property depends in large part on our ability to obtain and maintain patents and other intellectual property protection in the United States and in other countries with respect to various proprietary elements of our product candidates, such as, for example, our product formulations and processes for manufacturing our products and our ability to maintain and control the confidentiality of our trade secrets and confidential information critical to our business.
For example, 30 Table of Contents our ability to raise additional capital may be adversely impacted by global economic conditions and disruptions to and volatility in the credit and financial markets in the United States and worldwide, such as has been experienced recently due in part to, among other things, the impacts of inflation, ongoing overseas conflict, and disruptions in access to bank deposits and lending commitments due to bank failure.
For example, our ability to raise additional capital may be adversely impacted by global economic conditions and disruptions to and volatility in the credit and financial markets in the United States and worldwide, such as has been experienced recently due in part to, among other things, the impacts of inflation, ongoing overseas conflict, and disruptions in access to bank deposits and lending commitments due to bank failure.
In addition, while we typically require our employees, consultants and contractors who may be involved in the development of intellectual property to execute agreements assigning such intellectual property to us, we may be 57 Table of Contents unsuccessful in executing such an agreement with each party who in fact develops intellectual property that we regard as our own, which may result in claims by or against us asserting ownership of such intellectual property.
In addition, while we typically require our employees, consultants and contractors who may be involved in the development of intellectual property to execute agreements assigning such intellectual property to us, we may be unsuccessful in executing such an agreement with each party who in fact develops intellectual property that we regard as our own, which may result in claims by or against us asserting ownership of such intellectual property.
Further, because patent applications in the United States and most other countries are confidential for a period of time, 58 Table of Contents typically for 18 months after filing, we cannot be certain that we were the first to either (i) file any patent application related to our product candidates or (ii) invent any of the inventions claimed in our patents or patent applications.
Further, because patent applications in the United States and most other countries are confidential for a period of time, typically for 18 months after filing, we cannot be certain that we were the first to either (i) file any patent application related to our product candidates or (ii) invent any of the inventions claimed in our patents or patent applications.
In such an event, we may be held liable for any resulting damages and such liability could exceed our resources and state or federal or other applicable authorities may curtail our use of certain materials and/or interrupt our business operations. Furthermore, environmental laws and regulations are complex, change frequently and have tended to become more stringent.
In such an event, we may be held liable for any resulting damages and such liability could exceed our resources and state or federal or other applicable authorities may curtail our use of certain materials and/or interrupt our business operations. Furthermore, environmental laws and regulations are complex, change frequently and have tended to become more 69 Table of Contents stringent.
If we, any of our CROs, service providers or investigators fail to comply with applicable regulations or GCPs, the data generated in our preclinical and clinical trials may be deemed unreliable and the FDA, MHRA, EMA, European Commission, or comparable foreign regulatory authorities may require us to perform additional preclinical and clinical trials before approving our marketing applications.
If we, any of our CROs, service providers or investigators fail to comply with applicable 50 Table of Contents regulations or GCPs, the data generated in our preclinical and clinical trials may be deemed unreliable and the FDA, MHRA, EMA, European Commission, or comparable foreign regulatory authorities may require us to perform additional preclinical and clinical trials before approving our marketing applications.
However, the America Invents Act and its implementation could increase the uncertainties and costs surrounding the prosecution of 60 Table of Contents our patent applications and the enforcement or defense of any issued patents, all of which could harm our business and financial condition. Further, recent court rulings in cases such as Association for Molecular Pathology v. Myriad Genetics, Inc.
However, the America Invents Act and its implementation could increase the uncertainties and costs surrounding the prosecution of our patent applications and the enforcement or defense of any issued patents, all of which could harm our business and financial condition. Further, recent court rulings in cases such as Association for Molecular Pathology v. Myriad Genetics, Inc.
If these policies, materials or statements are found to be deficient, lacking in transparency, deceptive, unfair, or misrepresentative of our practices, we may be subject to investigation, enforcement actions by regulators, or other adverse consequences. 73 Table of Contents Obligations related to data privacy and security (and consumers’ data privacy expectations) are quickly changing, becoming increasingly stringent, and creating uncertainty.
If these policies, materials or statements are found to be deficient, lacking in transparency, deceptive, unfair, or misrepresentative of our practices, we may be subject to investigation, enforcement actions by regulators, or other adverse consequences. Obligations related to data privacy and security (and consumers’ data privacy expectations) are quickly changing, becoming increasingly stringent, and creating uncertainty.
We may also be unable to expand our operations or otherwise capitalize on our business opportunities, as desired, which could harm our business, financial condition and results of operations. ​ Raising additional capital, including modifications to our existing convertible securities, may cause dilution to our securityholders, restrict our operations or require us to relinquish rights to our technologies or product candidates.
We may also be unable to expand our operations or otherwise capitalize on our business opportunities, as desired, which could harm our business, financial condition and results of operations. ​ 30 Table of Contents Raising additional capital, including modifications to our existing convertible securities, may cause dilution to our securityholders, restrict our operations or require us to relinquish rights to our technologies or product candidates.
We re-submitted the BLA to the FDA for ONS-5010/LYTENAVA on August 30, 2022. On August 29, 2023, we received a CRL in which the FDA concluded it could not approve the BLA during this review cycle due to several CMC issues, open observations from pre-approval manufacturing inspections, and a lack of substantial evidence.
We re-submitted the BLA to the FDA for ONS-5010/LYTENAVA in August 2022 and in August 2023, we received a CRL in which the FDA concluded it could not approve the BLA during this review cycle due to several CMC issues, open observations from pre-approval manufacturing inspections, and a lack of substantial evidence.
As further discussed in the Risk Factor above entitled “We and certain of our officers have been named as defendants in a pending securities class action lawsuit. Certain of our officers and directors have also been named as defendants in a pending shareholder derivative action.
As further discussed in the Risk Factor above entitled “We and certain of our current and former officers have been named as defendants in a pending securities class action lawsuit. Certain of our officers and directors have also been named as defendants in a pending shareholder derivative action.
Undesirable side effects caused by a product candidate could result in the delay, suspension or termination of clinical trials by us or the FDA or supranational or comparable foreign regulatory authorities for a number of reasons, or could result in a delay of FDA or comparable foreign regulatory authority approval, similar to our withdrawal of our BLA in May 2022 to provide additional information requested by the FDA.
Undesirable side effects caused by a product candidate could result in the delay, suspension or termination of clinical trials by us or the FDA or supranational or comparable foreign regulatory authorities for a number of reasons, or could result in a delay of FDA or comparable foreign regulatory authority approval, similar to our withdrawal of our BLA in May 2022 to provide additional information requested by the FDA and subsequent CRLs.
In addition, if we or our future collaborators experience excess inventory, it may be necessary to write down or write off such excess inventory or incur an impairment charge with respect to the facility where such product is manufactured, which could adversely affect our operating results. ​ 50 Table of Contents Risks Related to Our Reliance on Third Parties We rely on third parties to conduct our preclinical and clinical trials and perform other tasks for us.
In addition, if we or our future collaborators experience excess inventory, it may be necessary to write down or write off such excess inventory or incur an impairment charge with respect to the facility where such product is manufactured, which could adversely affect our operating results. ​ Risks Related to Our Reliance on Third Parties We rely on third parties to conduct our preclinical and clinical trials and perform other tasks for us.
Additionally, sensitive data of the Company could be leaked, 75 Table of Contents disclosed, or revealed as a result of or in connection with our employees’, personnel’s, or vendors’ use of generative AI technologies. ​ Risks Related to Ownership of Our Securities The trading price of our securities is likely to be volatile, and purchasers of our securities could incur substantial losses.
Additionally, sensitive data of the Company could be leaked, disclosed, or revealed as a result of or in connection with our employees’, personnel’s, or vendors’ use of generative AI technologies. ​ Risks Related to Ownership of Our Securities The trading price of our securities is likely to be volatile, and purchasers of our securities could incur substantial losses.
We believe that quarterly comparisons of our financial results are not necessarily meaningful and should not be relied upon as an indication of our future performance. 78 Table of Contents If securities or industry analysts do not publish research, or publish unfavorable research, about our business, the market price of our securities and trading volume could decline.
We believe that quarterly comparisons of our financial results are not necessarily meaningful and should not be relied upon as an indication of our future performance. If securities or industry analysts do not publish research, or publish unfavorable research, about our business, the market price of our securities and trading volume could decline.
As a result, our business and operating results may be harmed. 47 Table of Contents The third-party coverage and reimbursement status of newly approved products is uncertain. Failure to obtain or maintain adequate coverage and reimbursement for new or current products could limit our ability to market those products and decrease our ability to generate revenue.
As a result, our business and operating results may be harmed. The third-party coverage and reimbursement status of newly approved products is uncertain. Failure to obtain or maintain adequate coverage and reimbursement for new or current products could limit our ability to market those products and decrease our ability to generate revenue.
The legal systems of certain countries, particularly certain developing countries, do not favor the enforcement of patents, trade secrets and other intellectual property protection, which could make it difficult for us to stop the infringement of our patents or marketing of competing products in violation of our proprietary rights generally.
The legal systems of certain countries, particularly certain developing countries, do not favor the enforcement of patents, trade secrets and other intellectual property protection, which could make it difficult for us to stop the 59 Table of Contents infringement of our patents or marketing of competing products in violation of our proprietary rights generally.
While we have filed patent applications to protect certain aspects of our own proprietary formulation and process developments, we also rely on trade secret protection and confidentiality agreements to protect proprietary scientific, business and technical information and know-how that is not or may not be patentable or that we elect not to patent.
While we have filed patent applications to protect certain aspects of our own proprietary formulation and process developments, we also rely on trade secret protection and confidentiality agreements to protect proprietary scientific, 60 Table of Contents business and technical information and know-how that is not or may not be patentable or that we elect not to patent.
We expect to experience pricing pressures in connection with the sale of ONS-5010/LYTENAVA, or any other product candidates we may develop in the future, if approved, due to the trend toward managed healthcare, the increasing influence of health maintenance organizations and additional legislative changes.
We expect to experience pricing pressures in connection with the sale of ONS-5010/LYTENAVA, or any other product candidates we may develop in the future, if approved, due to the trend 48 Table of Contents toward managed healthcare, the increasing influence of health maintenance organizations and additional legislative changes.
The total addressable market opportunity for our product candidates will ultimately depend upon a number of factors including the diagnosis and treatment criteria included in the final label, if approved for sale in specified indications, acceptance by the medical community, patient access and product pricing and reimbursement.
The total addressable market opportunity for our product candidates will ultimately depend upon a number of factors including the diagnosis and treatment criteria included in the final label, if approved for sale in specified indications, 49 Table of Contents acceptance by the medical community, patient access and product pricing and reimbursement.
Additionally, general supply chain issues may be exacerbated during disease outbreaks, epidemics or pandemics and may also impact the ability of our clinical trial sites to obtain basic medical supplies used in our trials in a timely fashion, if at all.
Additionally, general supply chain issues may be exacerbated during disease outbreaks, 62 Table of Contents epidemics or pandemics and may also impact the ability of our clinical trial sites to obtain basic medical supplies used in our trials in a timely fashion, if at all.
Additional debt financing, if available, may involve agreements that include covenants limiting or restricting our ability 31 Table of Contents to take specific actions, such as incurring additional debt, making capital expenditures or declaring dividends, and may be secured by all or a portion of our assets.
Additional debt financing, if available, may involve agreements that include covenants limiting or restricting our ability to take specific actions, such as incurring additional debt, making capital expenditures or declaring dividends, and may be secured by all or a portion of our assets.
Additionally, the milestone and other payments associated with these licenses will make it less profitable for us to develop our product candidates. In the event we breach any of our obligations under these agreements, we may incur significant liability to our licensing partners.
Additionally, the milestone and other payments associated with these licenses will make it less profitable for us to develop our product candidates. 61 Table of Contents In the event we breach any of our obligations under these agreements, we may incur significant liability to our licensing partners.
Coverage decisions may depend upon clinical and economic standards that disfavor new drug products when more established or lower cost therapeutic alternatives are already available or subsequently become available. Even if coverage is provided, the approved reimbursement amount may not be adequate to allow us to realize a return on our investment.
Coverage decisions may depend upon clinical and economic 47 Table of Contents standards that disfavor new drug products when more established or lower cost therapeutic alternatives are already available or subsequently become available. Even if coverage is provided, the approved reimbursement amount may not be adequate to allow us to realize a return on our investment.
We cannot predict the number, timing or size of future joint ventures or acquisitions, or the effect that any such transactions might have on our operating results. 70 Table of Contents We may pursue the development of our product candidates in combination with other approved therapeutics.
We cannot predict the number, timing or size of future joint ventures or acquisitions, or the effect that any such transactions might have on our operating results. We may pursue the development of our product candidates in combination with other approved therapeutics.
The term “submarine” patent has been used in the pharmaceutical industry and in other industries to denote a patent issuing from a U.S. application with an effective filing date prior to June 8, 1995 that was not published, publicly known or available prior to its grant. Submarine patents add substantial risk and uncertainty to our business.
The term “submarine” patent has been used in the pharmaceutical industry and in other industries to denote a patent issuing from a United States application with an effective filing date prior to June 8, 1995 that was not published, publicly known or available prior to its grant. Submarine patents add substantial risk and uncertainty to our business.
We may 36 Table of Contents also fail to appreciate that we have become aware of a reportable adverse event, especially if it is not reported to us as an adverse event or if it is an adverse event that is unexpected or removed in time from the use of our products.
We may also fail to appreciate that we have become aware of a reportable adverse event, especially if it is not reported to us as an adverse event or if it is an adverse event that is unexpected or removed in time from the use of our products.
As such, we may be required to hire substantially more sales representatives and medical support liaisons to adequately support the commercialization of ONS-5010/LYTENAVA or we may incur excess costs as a result of hiring more sales representatives than necessary.
As such, we may be required to hire substantially more sales representatives and medical support liaisons to adequately support the commercialization of ONS-5010/LYTENAVA or we may incur excess 46 Table of Contents costs as a result of hiring more sales representatives than necessary.
Grounds for an unenforceability assertion could include an allegation that someone involved in the prosecution of the patent withheld relevant or material information related to the patentability of the invention from the USPTO or made a misleading statement during prosecution.
Grounds for an unenforceability assertion could include an allegation that someone involved in the prosecution of the patent withheld relevant or material 56 Table of Contents information related to the patentability of the invention from the USPTO or made a misleading statement during prosecution.
If we fail in defending any such claims, in addition to paying monetary damages, 61 Table of Contents we may lose valuable intellectual property rights, such as exclusive ownership of or right to use valuable intellectual property. Such an outcome could harm our business.
If we fail in defending any such claims, in addition to paying monetary damages, we may lose valuable intellectual property rights, such as exclusive ownership of or right to use valuable intellectual property. Such an outcome could harm our business.
For example, on August 16, 2022, President Biden signed the IRA, into law, which among other things, extends enhanced subsidies for individuals purchasing health insurance coverage in Affordable Care Act marketplaces through plan year 2025.
For example, on August 16, 2022, the IRA was signed into law, which among other things, extends enhanced subsidies for individuals purchasing health insurance coverage in Affordable Care Act marketplaces through plan year 2025.
Any such issuance, including pursuant to any at-the-market agreements, could result in substantial dilution to our existing stockholders and could cause the price of our common stock to decline. Item 1B. Unresolved Staff Comments Not applicable.
Any such issuance, including pursuant to any at-the-market agreements, could result in substantial dilution to our existing stockholders and could cause the price of our common stock to decline. 82 Table of Contents Item 1B. Unresolved Staff Comments Not applicable.
In addition, supply-chain attacks have increased in frequency and severity, and we cannot guarantee that third parties’ infrastructure in our supply chain or our third-party partners’ supply chains have not been compromised. While we have implemented security measures designed to protect against security incidents, there can be no assurance that these measures will be effective.
In addition, supply-chain attacks have increased in frequency and severity, and we cannot guarantee that third parties’ infrastructure in our supply chain or our third-party partners’ supply chains have not been compromised. 74 Table of Contents While we have implemented security measures designed to protect against security incidents, there can be no assurance that these measures will be effective.
Our projections of the number of people who have the diseases we are seeking to treat, as well as the subset of people with these diseases who have the potential to benefit from treatment with our product candidates, are estimates based on our 49 Table of Contents knowledge and understanding of these diseases.
Our projections of the number of people who have the diseases we are seeking to treat, as well as the subset of people with these diseases who have the potential to benefit from treatment with our product candidates, are estimates based on our knowledge and understanding of these diseases.
If we are unable to manufacture or have manufactured sufficient supplies of ONS-5010/LYTENAVA or any other product candidates, our development 51 Table of Contents efforts would be delayed, which would adversely affect our business and prospects.
If we are unable to manufacture or have manufactured sufficient supplies of ONS-5010/LYTENAVA or any other product candidates, our development efforts would be delayed, which would adversely affect our business and prospects.
In addition to infringement claims against us, we may become a party to other patent litigation and other proceedings, including interference, derivation or post-grant proceedings declared or granted by the USPTO and similar proceedings in 55 Table of Contents foreign countries, regarding intellectual property rights with respect to our current or future products.
In addition to infringement claims against us, we may become a party to other patent litigation and other proceedings, including interference, derivation or post-grant proceedings declared or granted by the USPTO and similar proceedings in foreign countries, regarding intellectual property rights with respect to our current or future products.
The issuance of one or more submarine patents may harm our business by causing substantial delays in our ability to introduce a candidate into the U.S. market. We may not identify relevant patents or may incorrectly interpret the relevance, scope or expiration of a patent, which might adversely affect our ability to develop and market our products.
The issuance of one or more submarine patents may harm our business by causing substantial delays in our ability to introduce a candidate into the United States market. We may not identify relevant patents or may incorrectly interpret the relevance, scope or expiration of a patent, which might adversely affect our ability to develop and market our products.
Accordingly, our efforts to enforce our intellectual property rights around the world may be inadequate to obtain a significant commercial advantage from the intellectual property that we develop or license. Changes in U.S. patent law could diminish the value of patents in general, thereby impairing our ability to protect our product candidates.
Accordingly, our efforts to enforce our intellectual property rights around the world may be inadequate to obtain a significant commercial advantage from the intellectual property that we develop or license. Changes in United States patent law could diminish the value of patents in general, thereby impairing our ability to protect our product candidates.
The cost to us of any patent litigation or other proceeding, even if resolved in our favor, could be substantial. Patent litigation and other proceedings may fail, and even if successful, may result in substantial costs and distract our management and other employees.
The cost to us of any patent litigation or other proceeding, even if resolved in our favor, could be substantial. Patent litigation and other proceedings may fail, and even if successful, may result in substantial costs and distract our 55 Table of Contents management and other employees.
These laws may impact, among other things, our clinical research, proposed sales, marketing, charitable donations and grants, education programs and patient assistance. In addition, we may be subject to 67 Table of Contents patient data privacy and security regulation by both the federal government and the states in which we conduct our business.
These laws may impact, among other things, our clinical research, proposed sales, marketing, charitable donations and grants, education programs and patient assistance. In addition, we may be subject to patient data privacy and security regulation by both the federal government and the states in which we conduct our business.
The impact of these events could also make it more difficult for us to attract and retain qualified persons to serve on our board of directors, on committees of our board of directors or as members of senior management.
The impact of these 79 Table of Contents events could also make it more difficult for us to attract and retain qualified persons to serve on our board of directors, on committees of our board of directors or as members of senior management.
Doing business internationally involves a number of risks, including but not limited to: ● multiple, conflicting and changing laws and regulations such as privacy regulations, tax laws, export and import restrictions, employment laws, regulatory requirements and other governmental approvals, permits and licenses; ● failure by us or our collaboration partners to obtain and maintain regulatory approvals for the use of our products in various countries; ● additional potentially relevant third-party patent rights; ● complexities and difficulties in obtaining protection and enforcing our intellectual property; ● difficulties in staffing and managing foreign operations by us or our collaboration partners; ● complexities associated with managing multiple payor reimbursement regimes, government payors or patient self-pay systems by our collaboration partners; ● limits in our or our collaboration partners’ ability to penetrate international markets; ● financial risks, such as longer payment cycles, difficulty collecting accounts receivable, the impact of local and regional financial crises on demand and payment for our products and exposure to foreign currency exchange rate fluctuations; ● natural disasters, political and economic instability, including wars, terrorism and political unrest, outbreak of disease, boycotts, curtailment of trade and other business restrictions; ● certain expenses including, among others, expenses for travel, translation and insurance; and ● regulatory and compliance risks that relate to maintaining accurate information and control over sales and activities that may fall within the purview of the U.S.
Doing business internationally involves a number of risks, including but not limited to: ● multiple, conflicting and changing laws and regulations such as privacy regulations, tax laws, export and import restrictions, employment laws, regulatory requirements and other governmental approvals, permits and licenses; ● failure by us or our collaboration partners to obtain and maintain regulatory approvals for the use of our products in various countries; ● additional potentially relevant third-party patent rights; ● complexities and difficulties in obtaining protection and enforcing our intellectual property; ● difficulties in staffing and managing foreign operations by us or our collaboration partners; ● complexities associated with managing multiple payor reimbursement regimes, government payors or patient self-pay systems by our collaboration partners; ● limits in our or our collaboration partners’ ability to penetrate international markets; ● financial risks, such as longer payment cycles, difficulty collecting accounts receivable, the impact of local and regional financial crises on demand and payment for our products and exposure to foreign currency exchange rate fluctuations; ● natural disasters, political and economic instability, including wars, terrorism and political unrest, outbreak of disease, boycotts, curtailment of trade and other business restrictions; ● certain expenses including, among others, expenses for travel, translation and insurance; and ● regulatory and compliance risks that relate to maintaining accurate information and control over sales and activities that may fall within the purview of the United States Foreign Corrupt Practices Act, its books and records provisions or its anti-bribery provisions, or comparable foreign requirements.
Because we rely, and continue to expect to rely on third parties to manufacture our current and any future product candidates, and we expect to continue to collaborate with third parties on the development of our current and any future 53 Table of Contents product candidates, we must, at times, share trade secrets with them.
Because we rely, and continue to expect to rely on third parties to manufacture our current and any future product candidates, and we expect to continue to collaborate with third parties on the development of our current and any future product candidates, we must, at times, share trade secrets with them.
See “Raising additional capital, including modifications to our existing convertible securities, may cause dilution to our securityholders, restrict our operations or require us to relinquish rights to our technologies and product candidates” for additional information on the effects of an event of default under the terms of the December 2022 Note.
See “Raising additional capital, including modifications to our existing convertible securities, may cause dilution to our securityholders, restrict our operations or require us to relinquish rights to our technologies and product candidates” for additional information on the effects of an event of default under the terms of the March 2025 Note.
Other products may be approved and successfully commercialized before ours, which may adversely affect our financial condition and our ability to successfully commercialize our product candidates. We expect to enter highly competitive pharmaceutical markets.
Other products may be approved and successfully commercialized before ours, which may adversely affect our financial condition and our ability to successfully commercialize our product candidates. We have entered and expect to continue to enter highly competitive pharmaceutical markets.
The CCPA and other comprehensive U.S. state privacy laws exempt some data processed in the context of clinical trials, but these developments may further complicate compliance efforts and increase legal risk and compliance costs for us and the third parties with whom we work.
The CCPA and other comprehensive United States state privacy laws exempt some data processed in the context of clinical trials, but these developments may further complicate compliance efforts and increase legal risk and compliance costs for us and the third parties with whom we work.
If we are unable to successfully complete development and obtain regulatory approval for ONS-5010/LYTENAVA outside the EU and UK , our business will be harmed. ​ 29 Table of Contents There is substantial doubt about our ability to continue as a going concern.
If we are unable to successfully complete development and obtain regulatory approval for ONS-5010/LYTENAVA outside the EU and UK , our business will be harmed. ​ There is substantial doubt about our ability to continue as a going concern.
We, as a company, have no experience selling and marketing 46 Table of Contents any pharmaceutical products. To successfully commercialize ONS-5010/LYTENAVA or any other products for which we receive approvals, we will need to develop these capabilities, either on our own or with others.
We, as a company, have no experience selling and marketing any pharmaceutical products. To successfully commercialize ONS-5010/LYTENAVA or any other products for which we receive approvals, we will need to develop these capabilities, either on our own or with others.
The class action complaint alleges violations of the Securities Exchange Act of 1934, as amended, or the Exchange Act, in connection with allegedly false and misleading statements made by us related to our BLA during the period from December 29, 2022 through August 29, 2023.
The class action complaint alleges violations of the Securities Exchange Act of 1934, as amended, or the Exchange Act, in connection with allegedly false and misleading statements made by us related to our BLA during the period from August 3, 2021 through August 29, 2023.

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Item 1C. Cybersecurity

Cybersecurity — threats and controls disclosure

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Biggest changeAs part of its oversight responsibilities, the Audit Committee receives periodic updates on cybersecurity and information technology matters and related risk exposures (including, as relevant, those stemming from certain cybersecurity incidents) from our Executive VP and Chief Financial Officer. ​ ​
Biggest changeAs part of its oversight responsibilities, the Audit Committee receives periodic updates on cybersecurity and information technology matters and 83 Table of Contents related risk exposures (including, as relevant, those stemming from certain cybersecurity incidents) from our Executive VP and Chief Financial Officer. ​
Risk Factors in this Annual Report on Form 10-K, including If our information technology systems or those of third parties with whom we work, or our data are or were compromised, we could experience adverse consequences resulting from such compromise, including but not limited to regulatory investigations or actions; litigation; fines and penalties; disruptions of our business operations; reputational harm; loss of revenue or profits; and other adverse consequences . ​ 83 Table of Contents Governance ​ Our cybersecurity risk assessment and management processes are implemented and maintained by certain management, including our Director of Information Technology, who has more than two decades of information technology and information technology leadership experience.
Risk Factors in this Annual Report on Form 10-K, including If our information technology systems or those of third parties with whom we work, or our data are or were compromised, we could experience adverse consequences resulting from such compromise, including but not limited to regulatory investigations or actions; litigation; fines and penalties; disruptions of our business operations; reputational harm; loss of revenue or profits; and other adverse consequences . ​ Governance ​ Our cybersecurity risk assessment and management processes are implemented and maintained by certain management, including our Director of Information Technology, who has more than two decades of information technology and information technology leadership experience.

Item 3. Legal Proceedings

Legal Proceedings — active lawsuits and investigations

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Biggest changeThe plaintiffs in the class action complaint seek damages and interest, and an award of reasonable costs, including attorneys’ fees. Defendants’ motion to dismiss is currently pending before the court. On October 10, 2024, certain of the company’s officers and directors were named as defendants in a shareholder derivative action filed in the District Court of the District of Delaware.
Biggest changeThe plaintiffs in the class action complaint seek damages and interest, and an award of reasonable costs, including attorneys’ fees. The defendants’ motion to dismiss the second amended complaint is currently pending before the court.
Our management believes that there are currently no additional claims or actions pending against us, the ultimate disposition of which would have a material adverse effect on our results of operations, financial condition or cash flows. Item 4. Mine Safety Disclosures Not applicable. ​ 85 Table of Contents PART II
Our management believes that there are currently no additional claims or actions pending against us, the ultimate disposition of which would have a material adverse effect on our results of operations, financial condition or cash flows. Item 4. Mine Safety Disclosures Not applicable. ​ 84 Table of Contents PART II
Such amounts could be material to our financial statements if we do not prevail in the defense of the pending lawsuits and any other related lawsuits, or even if 84 Table of Contents we do prevail. We have not established any reserve for any potential liability relating to the pending lawsuits and any other related lawsuits.
Such amounts could be material to our financial statements if we do not prevail in the defense of the pending lawsuits and any other related lawsuits, or even if we do prevail. We have not established any reserve for any potential liability relating to the pending lawsuits and any other related lawsuits.
The derivative complaint seeks unspecified damages, corporate governance reforms, restitution, contribution, attorneys’ fees, and other costs. The pending lawsuits and any other related lawsuits are subject to inherent uncertainties, and the actual defense and disposition costs will depend upon many unknown factors. The outcome of the pending lawsuits and any other related lawsuits is necessarily uncertain.
The pending lawsuits and any other related lawsuits are subject to inherent uncertainties, and the actual defense and disposition costs will depend upon many unknown factors. The outcome of the pending lawsuits and any other related lawsuits is necessarily uncertain.
Added
On October 10, 2024, certain of the company’s officers and directors were named as defendants in a shareholder derivative action filed in the District Court of the District of Delaware.
Added
The derivative complaint seeks unspecified damages, corporate governance reforms, restitution, contribution, attorneys’ fees, and other costs. The derivative action is currently stayed, pending the final resolution of the securities class action pending in the United States District Court for the District of New Jersey.

Item 5. Market for Registrant's Common Equity

Market for Common Equity — stock, dividends, buybacks

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Biggest changeItem 5. Market for Registrant’s Common Equity, Related Stockholder Matters, and Issuer Purchases of Equity Securities Market Information Our common stock is traded on The Nasdaq Capital Market under the symbol “OTLK”. Common Stockholders As of December 14, 2024, there were approximately 78 stockholders of record of our common stock.
Biggest changeItem 5. Market for Registrant’s Common Equity, Related Stockholder Matters, and Issuer Purchases of Equity Securities Market Information Our common stock is traded on The Nasdaq Capital Market under the symbol “OTLK”. Common Stockholders As of December 10, 2025, there were approximately 76 stockholders of record of our common stock.
Issuer Purchases of Equity Securities We did not repurchase any of our equity securities during fiscal year ended September 30, 2024. Item 6. Reserved. ​ 86 Table of Contents
Issuer Purchases of Equity Securities We did not repurchase any of our equity securities during fiscal year ended September 30, 2025. Item 6. Reserved. ​ 85 Table of Contents

Item 7. Management's Discussion & Analysis

Management's Discussion & Analysis (MD&A) — revenue / margin commentary

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Biggest changeThe increase was primarily due to an $8.6 million rise in development costs associated with ONS-5010/LYTENAVA related to the commencement and subsequent completion of enrollment in the NORSE EIGHT clinical trial, combined with the effects of a $6.2 million refund for BLA submission fees from the FDA received in the prior period. 93 Table of Contents General and Administrative Expenses The following table summarizes our general and administrative expenses by type for the years ended September 30, 2024 and 2023: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year ended September 30, ​ 2024 2023 Professional fees ​ $ 9,866,128 ​ $ 14,522,528 Compensation and related benefits ​ ​ 6,301,200 ​ ​ 4,366,447 Stock-based compensation ​ ​ 4,584,168 ​ ​ 4,560,421 Europe prelaunch expenses ​ ​ 5,010,687 ​ ​ — Facilities, fees and other related costs ​ ​ 4,178,005 ​ ​ 3,224,044 Total general and administrative expenses ​ $ 29,940,188 ​ $ 26,673,440 ​ General and administrative expenses for the year ended September 30, 2024 increased by $3.3 million compared to the year ended September 30, 2023.
Biggest changeSelling, general and administrative expenses The following table summarizes our general and administrative expenses by type for the years ended September 30, 2025 and 2024: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year ended September 30, ​ ​ ​ ​ 2025 ​ ​ ​ 2024 Professional fees ​ $ 6,173,453 ​ $ 9,866,128 Compensation and related benefits ​ ​ 8,177,077 ​ ​ 6,301,200 Stock-based compensation ​ ​ 8,480,292 ​ ​ 4,584,168 Europe launch expenses ​ ​ 13,377,691 ​ ​ 5,010,687 Facilities, fees and other related costs ​ ​ 3,729,718 ​ ​ 4,178,005 Total selling, general and administrative expenses ​ $ 39,938,231 ​ $ 29,940,188 ​ Selling, general and administrative expenses for the year ended September 30, 2025 increased by $10.0 million compared to the year ended September 30, 2024.
Under the BTIG ATM Agreement, we pay BTIG a commission equal to 3.0% of the aggregate gross proceeds of any sales of common stock under the BTIG ATM Agreement.
Under the ATM Agreement, we pay BTIG a commission equal to 3.0% of the aggregate gross proceeds of any sales of common stock under the ATM Agreement.
Financing Activities During the year ended September 30, 2024, net cash provided by financing activities was $60.3 million, primarily attributable to $60.3 million in net proceeds from private placements in March 2024 and April 2024 of an aggregate of 9,285,709 shares of our common stock and warrants to purchase an aggregate of 13,928,562 shares of our common stock.
During the year ended September 30, 2024, net cash provided by financing activities was $60.3 million, primarily attributable to $60.3 million in net proceeds from private placements in March 2024 and April 2024 of an aggregate of 9,285,709 shares of our common stock and warrants to purchase an aggregate of 13,928,562 shares of our common stock.
We received net proceeds of $18.1 million upon the closing on December 28, 2022, after deducting the Lender’s transaction costs in connection with the issuance and November 2021 Note repayment. In December 2023, the Company extended the maturity of the December 2022 Note from January 1, 2024 to April 1, 2024. The Company incurred a $475,000 extension fee.
We received net proceeds of $18.1 million upon the closing on December 28, 2022, after deducting the Lender’s transaction costs in connection with the issuance and November 2021 Note repayment. In December 2023, we extended the maturity of the December 2022 Note from January 1, 2024, to April 1, 2024. We incurred a $475,000 extension fee.
These expenses include: ● expenses incurred under agreements with contract research organizations, or CROs, as well as investigative sites and consultants that conduct our preclinical studies and clinical trials; ● expenses incurred by us directly, as well as under agreements with contract manufacturing organizations, or CMOs, for manufacturing scale-up expenses and the cost of acquiring and manufacturing preclinical and clinical trial materials and commercial materials, including manufacturing validation batches; ● outsourced professional scientific development services; 90 Table of Contents ● employee-related expenses, which include salaries, benefits and stock-based compensation; ● payments made under a third-party assignment agreement, under which we acquired intellectual property; ● expenses relating to regulatory activities, including filing fees paid to regulatory agencies; ● laboratory materials and supplies used to support our research activities; and ● allocated expenses, utilities and other facility-related costs. ​ The successful development of our product candidates is highly uncertain.
These expenses include: ● expenses incurred under agreements with contract research organizations, or CROs, as well as investigative sites and consultants that conduct our preclinical studies and clinical trials; ● expenses incurred by us directly, as well as under agreements with contract manufacturing organizations, or CMOs, for manufacturing scale-up expenses and the cost of acquiring and manufacturing preclinical and clinical trial materials and commercial materials, including manufacturing validation batches; ● outsourced professional scientific development services; ● employee-related expenses, which include salaries, benefits and stock-based compensation; ● payments made under a third-party assignment agreement, under which we acquired intellectual property; ● expenses relating to regulatory activities, including filing fees paid to regulatory agencies; ● laboratory materials and supplies used to support our research activities; and ● allocated expenses, utilities and other facility-related costs. ​ The successful development of our product candidates is highly uncertain.
Our future funding requirements will depend on many factors, including: ● the number and characteristics of the product candidates we pursue; ● the scope, progress, results and costs of researching and developing our product candidates, and conducting preclinical studies and clinical trials; ● the timing of, and the costs involved in, obtaining regulatory approvals for our product candidates; 99 Table of Contents ● the cost of manufacturing our product candidates and any drugs we successfully commercialize; ● our ability to establish and maintain strategic collaborations, licensing or other arrangements and the financial terms of such agreements; ● the costs involved in preparing, filing, prosecuting, maintaining, defending and enforcing patent claims, including litigation costs and the outcome of such litigation; ● expenses associated with the pending securities class action lawsuit, as well as other potential litigation; and ● the timing, receipt and amount of sales of, or milestone payments related to or royalties on, our current or future product candidates, if any.
Our future funding requirements will depend on many factors, including: ● the number and characteristics of the product candidates we pursue; ● the scope, progress, results and costs of researching and developing our product candidates, and conducting preclinical studies and clinical trials; ● the timing of, and the costs involved in, obtaining regulatory approvals for our product candidates; ● the cost of manufacturing our product candidates and any drugs we successfully commercialize; ● our ability to establish and maintain strategic collaborations, licensing or other arrangements and the financial terms of such agreements; ● the costs involved in preparing, filing, prosecuting, maintaining, defending and enforcing patent claims, including litigation costs and the outcome of such litigation; ● expenses associated with the pending securities class action lawsuit, as well as other pending and potential litigation; and ● the timing, receipt and amount of sales of, or milestone payments related to or royalties on, our current or future product candidates, if any.
A portion of the proceeds from the December 2022 Note were used to repay in full the remaining outstanding principal and accrued interest on the November 2021 Note, which was cancelled upon repayment.
A portion of the proceeds from the December 2022 Note was used to repay in full the remaining outstanding principal and accrued interest on the November 2021 Note, which was cancelled upon repayment.
The offering of common stock pursuant to the BTIG ATM Agreement will terminate upon the earlier of (i) the sale of all common stock subject to the BTIG ATM Agreement or (ii) termination of the BTIG ATM Agreement in accordance with its terms.
The offering of common stock pursuant to the ATM Agreement will terminate upon the earlier of (i) the sale of all common stock subject to the ATM Agreement or (ii) termination of the ATM Agreement in accordance with its terms.
In December 2023, we submitted a Special Protocol Assessment, or SPA, to the FDA for this study (NORSE EIGHT) seeking confirmation that, if successful, it will address the FDA’s requirement for a second adequate and well-controlled clinical trial to support our planned resubmission of the ONS-5010/LYTENAVA BLA.
In December 2023, we submitted a Special Protocol Assessment, or SPA, to the FDA for this study (NORSE EIGHT) seeking confirmation that, if successful, it would address the FDA’s requirement for a second adequate and well-controlled clinical trial to support our planned resubmission of the ONS-5010/LYTENAVA BLA.
While we expect that the majority of the cash payments related to the workforce reduction will be substantially complete by the third calendar quarter of 2025, we may incur other charges or cash expenditures not currently contemplated due to unanticipated events that may occur, including in connection with the implementation of the workforce reduction.
While we expect that the majority of the cash payments related to the workforce reduction in September 2025 will be substantially complete by the third calendar quarter of 2026, we may incur other charges or cash expenditures not currently contemplated due to unanticipated events that may occur, including in connection with the implementation of the workforce reduction.
At subsequent Type A meetings with the FDA, we learned that the FDA requires the completion of an additional adequate and well-controlled clinical trial evaluating ONS-5010/LYTENAVA, as well as additional requested CMC data indicated in the CRL to approve ONS-5010/LYTENAVA for use in wet AMD.
At subsequent Type A meetings with the FDA, we learned that the FDA required the completion of an additional adequate and well-controlled clinical trial evaluating ONS-5010/LYTENAVA, as well as additional requested CMC data indicated in the CRL to approve ONS-5010/LYTENAVA for use in wet AMD.
Alternatively, we will be required to, among other things, modify our clinical trial plans for ONS-5010/LYTENAVA in additional indications, make reductions in our workforce, scale back our plans and place certain activities on hold, discontinue our development programs, liquidate all or a portion of our assets, and/or seek protection under the provisions of the U.S. Bankruptcy Code.
Alternatively, we will be required to, among other things, modify our clinical trial plans for ONS-5010/LYTENAVA in additional indications, make reductions in our workforce, scale back our plans and place certain activities on hold, discontinue our development programs, liquidate all or a portion of our assets, and/or seek protection under the provisions of the United States Bankruptcy Code.
Change in Fair Value of Promissory Notes The change in fair value relates to convertible promissory notes that we elected to account for at fair value. As permitted under ASC 825, we elected the fair value option to account for our convertible promissory notes.
Loss from change in fair value of promissory notes The change in fair value relates to convertible promissory notes that we elected to account for at fair value. As permitted under ASC 825, we elected the fair value option to account for our convertible promissory notes.
Change in Fair Value of Promissory Notes The change in fair value relates to the convertible promissory notes that we elected to account for at fair value. As permitted under ASC 825, we elected the fair value option to account for our convertible promissory notes.
Loss from change in fair value of promissory notes The change in fair value relates to the convertible promissory notes that we elected to account for at fair value. As permitted under ASC 825, we elected the fair value option to account for our convertible promissory notes.
Additionally, we may not achieve the expected benefits of these cost reduction measures and other cost reduction plans on the anticipated timeline, or at all, which could otherwise accelerate our liquidity needs and could force us to further curtail or suspend our operations.
Additionally, we may not achieve the expected benefits of these cost reduction measures and other 97 Table of Contents cost reduction plans on the anticipated timeline, or at all, which could otherwise accelerate our liquidity needs and could force us to further curtail or suspend our operations.
We do not believe our current cash resources of $14.9 million as of September 30, 2024, together with $1.7 million in net proceeds from the sale of shares of common stock under the BTIG ATM Offering since September 30, 2024, are sufficient to fund our operations through one year from the Form 10-K filing date.
We do not believe our current cash resources of $8.1 million as of September 30, 2025, together with $14.9 million in net proceeds from the sale of shares of common stock under the BTIG ATM Offering since September 30, 2025, are sufficient to fund our operations through one year from the Form 10-K filing date.
We plan to finance our future operations with 89 Table of Contents a combination of proceeds from potential licensing and/or marketing arrangements with pharmaceutical companies, the issuance of equity securities and the issuance of additional debt, potential collaborations and revenues from potential future product sales, if any.
We plan to finance our future operations with a combination of proceeds from potential licensing and/or marketing arrangements with pharmaceutical companies, the issuance of equity securities and the issuance of additional debt, potential collaborations and revenues from potential future product sales, if any.
The agreements reached with the FDA on these SPAs cover the 88 Table of Contents protocols for NORSE FOUR, a registration clinical trial evaluating ONS-5010/LYTENAVA to treat BRVO, and NORSE FIVE and NORSE SIX, two registration clinical trials evaluating ONS-5010/LYTENAVA to treat DME. The timing for initiating these studies has not been determined pending initial FDA approval for wet AMD.
The agreements reached with the FDA on these SPAs cover the protocols for NORSE FOUR, a registration clinical trial evaluating ONS-5010/LYTENAVA to treat BRVO, and NORSE FIVE and NORSE SIX, two registration clinical trials evaluating ONS-5010/LYTENAVA to treat DME. The timing for initiating these studies has not been determined pending initial FDA approval for wet AMD.
We base our expenses related to preclinical studies and clinical trials on our estimates of the services received and efforts expended pursuant to quotes and contracts with multiple research institutions and CROs that conduct and manage 100 Table of Contents preclinical studies and clinical trials on our behalf.
We base our expenses related to preclinical studies and clinical trials on our estimates of the services received and efforts expended pursuant to quotes and contracts with multiple research institutions and CROs that conduct and manage preclinical studies and clinical trials on our behalf.
Alternatively, we will be required to, among other things, make reductions in our workforce, scale back our plans and place certain activities on hold, discontinue our development programs, liquidate all or a portion of our assets, and/or seek protection under the provisions of the U.S. Bankruptcy Code.
Alternatively, we will be required to, among other things, make reductions in our workforce, scale back our plans and place certain activities on hold, discontinue our development programs, liquidate all or a portion of our assets, and/or seek protection under the provisions of the United States Bankruptcy Code.
On December 22, 2022, we entered into a Securities Purchase Agreement and issued an unsecured convertible promissory note with a face amount of $31.8 million, or the December 2022 Note, to Streeterville Capital, LLC, or the Lender, the holder of our November 2021 Note. The December 2022 Note has an original issue discount of $1.8 million.
On December 22, 2022, we entered into a Securities Purchase Agreement and issued an unsecured convertible promissory note with a face amount of $31.8 million, or the December 2022 Note, to Streeterville Capital, LLC, or the Lender, who was the holder of our November 2021 Note. The December 2022 Note had an original issue discount of $1.8 million.
Under the January 2024 Note Amendment, the initial conversion price with respect to $15.0 million in aggregate principal amount of the December 2022 Note was changed to $7.00, the price per share in the private placement that closed on March 18, 2024 and the remaining aggregate principal amount has a conversion price of $40.00 per share.
Under the Note Amendment, the initial conversion price with respect to $15.0 million in aggregate principal amount of the December 2022 Note was changed to $7.00, the price per share in the private placement that closed on March 18, 2024, and the remaining aggregate principal amount was converted at a price of $40.00 per share.
The maturity of the December 2022 Note was extended to July 1, 2025. An extension fee of $2.7 million (calculated as 7.5% of the outstanding balance of the December 2022 Note) was added to the outstanding balance on March 18, 2024.
The maturity of the December 2022 Note was extended to July 1, 2025. An extension fee of $2.7 million 95 Table of Contents (calculated as 7.5% of the outstanding balance of the December 2022 Note) was added to the outstanding balance on March 18, 2024.
We do not believe our existing cash and cash equivalents of $14.9 million as of September 30, 2024, together with $1.7 million in net proceeds from the sale of shares of common stock under the BTIG ATM Offering since September 30, 2024, are sufficient to fund our operations through one year from the Form 10-K filing date.
We do not believe our existing cash and cash equivalents of $8.1 million as of September 30, 2025, together with $14.9 million in net proceeds from the sale of shares of common stock under the ATM Offering since September 30, 2025, are sufficient to fund our operations through one year from the Form 10-K filing date.
On August 29, 2023, we received a Complete Response Letter, or CRL, in which the FDA concluded it could not approve the BLA during this review cycle due to several chemical, manufacturing and control, or CMC, issues, open observations from pre-approval manufacturing inspections, and a lack 87 Table of Contents of substantial evidence.
In August 2023, we received a Complete Response Letter, or CRL, in which the FDA concluded it could not approve the BLA during this review cycle due to several chemical, manufacturing and control, or CMC, issues, open observations from pre-approval manufacturing inspections, and a lack of substantial evidence.
Through September 30, 2024, we have funded substantially all of our operations with $530.9 million in net proceeds from the sale and issuance of our equity securities, debt securities and borrowings under debt facilities. We anticipate incurring additional losses until such time, if ever, that we can generate significant sales of ONS-5010/LYTENAVA or any other product candidate we may develop.
Through September 30, 2025, we have funded substantially all of our operations with $612.0 million in net proceeds from the sale and issuance of our equity securities, debt securities and borrowings under debt facilities. We anticipate incurring additional losses until such time, if ever, that we can generate significant sales of ONS-5010/LYTENAVA or any other product candidate we may develop.
On January 22, 2024, the Company entered into an amendment to the December 2022 Note (the “January 2024 Note Amendment”) with the Lender, which became effective on April 1, 2024 after satisfaction of certain closing conditions, including various required stockholder approvals and the closing of the private placement that closed on March 18, 2024.
On January 22, 2024, we entered into an amendment to the December 2022 Note, or the Note Amendment, with the Lender, which became effective on April 1, 2024, after the satisfaction of certain closing conditions, including various required stockholder approvals and the closing of the private placement that closed on March 18, 2024.
In November 2024, we reported that ONS-5010/LYTENAVA did not meet the pre-specified non-inferiority endpoint at week 8 set forth in the special protocol assessment (SPA) with the FDA. However, the preliminary data from the trial demonstrated an improvement in vision and the presence of biologic activity, as well as a continued favorable safety profile for ONS-5010.
In November 2024, we reported that ONS-5010/LYTENAVA did not meet the pre-specified non-inferiority endpoint at week 8 set forth in the SPA. However, the data from the trial demonstrated an improvement in vision and the presence of biologic activity, as well as a continued favorable safety profile for ONS-5010/LYTENAVA.
Income Taxes Since inception, we have not recorded any U.S. federal or state income tax benefits (excluding the sale of New Jersey state NOLs and research and development, or R&D, tax credits) for the net losses we have incurred in each year or on our earned R&D tax credits, due to our uncertainty of realizing a benefit from those items.
Since inception, we have not recorded any United States federal or state income tax benefits (excluding the sale of New Jersey state NOLs and research credits) for the net losses we have incurred in each year or on our earned research and development tax credits, due to our uncertainty of realizing a benefit from those items.
Our existing NOLs may be subject to limitations arising from previous ownership changes, and if we undergo an ownership change in connection with or 92 Table of Contents after our Initial Public Offering, or IPO, our ability to utilize NOLs could be further limited by Section 382 of the Code.
Our existing NOLs may be subject to limitations arising from previous ownership changes, and if we undergo an ownership change in connection with or after our IPO, our ability to utilize NOLs could be further limited by Section 382 of the Code.
See Item 1A “Risk Factors” for additional risks associated with our substantial capital requirements . Critical Accounting Policies and Significant Judgments and Estimates Our consolidated financial statements are prepared in accordance with U.S. generally accepted accounting principles, or GAAP.
See Item 1A “Risk Factors” for additional risks associated with our substantial capital requirements . 100 Table of Contents Critical Accounting Policies and Significant Judgments and Estimates Our consolidated financial statements are prepared in accordance with United States generally accepted accounting principles, or GAAP.
Effective April 1 2024, the December 2022 Note bears interest at the prime rate (as published in the Wall Street Journal) plus 3% (subject to a floor of 9.5%) and the Company has an obligation to repay at least $3.0 million of the outstanding balance of the December 2022 Note for each calendar quarter beginning with the second calendar quarter of 2024 (subject to adjustment for conversions by the Lender and to payment of an exit fee as set forth in the December 2022 Note) and continuing until the December 2022 Note is repaid in full.
Effective April 1, 2024, the December 2022 Note bore interest at the prime rate (as published in the Wall Street Journal) plus 3% (subject to a floor of 9.5%), and we had an obligation to repay at least $3.0 million (by either cash or conversion into common stock) of the outstanding balance of the December 2022 Note for each calendar quarter beginning with the second calendar quarter of 2024 (subject to adjustment for conversions by the Lender and to payment of an exit fee as set forth in the December 2022 Note) and continuing until the December 2022 Note was repaid in full.
As agreed to with the FDA in the SPA, NORSE EIGHT is a randomized, controlled, parallel-group, masked, non-inferiority study of approximately 400 newly diagnosed, wet AMD subjects randomized in a 1:1 ratio to receive 1.25 mg ONS-5010/LYTENAVA or 0.5 mg ranibizumab intravitreal injections. Subjects received injections at Day 0 (randomization), Week 4, and Week 8 visits.
NORSE EIGHT As agreed to with the FDA in the SPA, NORSE EIGHT was a randomized, controlled, parallel-group, masked, non-inferiority study of approximately 400 newly diagnosed, wet AMD subjects randomized in a 1:1 ratio to receive 1.25 mg ONS-5010/LYTENAVA or 0.5 mg ranibizumab intravitreal injections.
The warrants are subject to re-measurement at each balance sheet date and we recognize any change in fair value in our statements of operations as other (income) expense.
These warrants are categorized as liabilities and recorded at fair value. The warrants are subject to re-measurement at each balance sheet date, and we recognize any change in fair value in our statements of operations.
The guidance in ASU 2023-09 will be effective for annual reporting periods in fiscal years beginning after December 15, 2024. We are currently evaluating the impact that the adoption of ASU 2023-09 will have on its consolidated financial statements and disclosures.
The guidance in ASU 2023-09 will be effective for annual reporting periods in fiscal years beginning after December 15, 2024. We are currently evaluating the impact that the adoption of ASU 2023-09 will have on our consolidated financial statements and disclosures. In November 2024, the FASB issued ASU 2024-03, Disaggregation of Income Statement Expenses .
Interest Income Interest income for the year ended September 30, 2024 and 2023 was earned from short term investments, primarily consisting of money market investments. Interest Expense Interest expense for the year ended September 30, 2024 increased by $0.6 million compared to prior year.
Interest income Interest income for the year ended September 30, 2025 and 2024 was earned from short term investments, primarily consisting of money market investments. Interest expense Interest expense for the year ended September 30, 2025 decreased by $2.9 million compared to prior year.
We issued warrants to purchase our common stock in conjunction with convertible senior secured notes issued pursuant to a certain Note and Warrant Purchase Agreement dated December 22, 2017. Additionally, we issued warrants in connection with private placements that closed on March 18, 2024 and April 15, 2024. These warrants are categorized as liabilities and recorded at fair value.
Gain from change in fair value of warrant liability We issued warrants to purchase our common stock in conjunction with convertible senior secured notes issued pursuant to a certain Note and Warrant Purchase Agreement dated December 22, 2017. Additionally, we issued warrants in connection with private placements that closed on March 18, 2024 and April 15, 2024.
On May 16, 2023, we entered into the BTIG ATM Agreement, under which we may issue and sell shares of common stock having an aggregate offering price of up to $100.0 million from time to time through BTIG.
On May 16, 2023, we entered into an At-the-Market Sales Agreement with BTIG, LLC, or BTIG, as sales agent, as amended, the ATM Agreement or the ATM Offering, under which we may issue and sell shares of our common stock having an aggregate offering price of up to $100.0 million from time to time through BTIG.
As of September 30, 2024, we also had federal and state R&D tax credit carryforwards of $13.0 million and $0.8 million, respectively, that will begin to expire in 2032 and 2033, respectively.
As of September 30, 2025, we also had federal and state research and development tax credit carryforwards of $11.6 million and $0.8 million, respectively, that will begin to expire in 2032 and 2033, respectively.
The submission was completed under the new International Recognition Procedure (IRP), which allows the MHRA to rely on an authorization received for the same product from one of MHRA’s specified Reference Regulators (RRs) when considering an application for marketing authorization in the UK.
In July 2024, the MHRA granted marketing authorization for ONS-5010/LYTENAVA for the treatment of wet AMD in the UK under the new International Recognition Procedure, or IRP, which allows the MHRA to rely on an authorization received for the same product from one of MHRA’s specified Reference Regulators, or RRs, when considering an application for marketing authorization in the UK.
There can be no assurance that these future funding efforts will be successful. Alternatively, we will be required to, among other things, make reductions in our workforce, scale back our plans and place certain activities on hold, discontinue our development programs, liquidate all or a portion of our assets, and/or seek protection under the provisions of the U.S.
Alternatively, we will be required to, among other things, make reductions in our workforce, scale back our plans and place certain activities on hold, discontinue our development programs, liquidate all or a portion of our assets, and/or seek protection under the provisions of the United States Bankruptcy Code .
During the year ended September 30, 2023, we used $43.0 million of cash in operating activities resulting primarily from our net loss of $59.0 million.
During the year ended September 30, 2024, we used $68.8 million of cash in operating activities resulting primarily from our net loss of $75.4 million.
The net cash inflow of $4.8 million from changes in our operating assets and liabilities was primarily due to a net increase in accounts payable and accrued expenses of $2.4 million and a decrease in prepaid expenses of $2.6 million related to timing of payments associated with ONS-5010/LYTENAVA development costs, partially offset by an increase in other assets of $0.2 million.
The net cash inflow of $4.9 million from changes in our operating assets and liabilities was primarily due to a decrease in prepaid expenses of $8.0 million associated mainly with ONS-5010/LYTENAVA development costs relating to clinical trial and drug development costs, and an increase in accounts payable and accrued expenses of $3.4 million, primarily due to timing of payments, partially offset by a decrease in income taxes payable of $1.6 million, an increase in inventory of $3.3 million relating to commercial inventory manufactured during the period and accounts receivable of $1.5 million.
This use of cash was partially offset by $12.4 million of non-cash items such as stock-based compensation, non-cash interest expense, change in fair value of promissory notes, change in fair value of warrant liability, 97 Table of Contents loss on extinguishment of debt, loss on equity method investment and depreciation and amortization expense.
This use of cash was partially offset by $5.7 million of non-cash items such as stock-based compensation, loss from change in fair value of promissory notes, warrant inducement expenses, gain from change in fair value of warrant liability, loss on equity method investment and amortization expense.
Cash Flows The following table summarizes our cash flows for each of the years presented: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year ended September 30, ​ 2024 2023 Net cash used in operating activities ​ $ (68,793,858) ​ $ (42,973,398) Net cash provided by financing activities ​ ​ 60,329,414 ​ ​ 48,968,568 Net (decrease) increase in cash and cash equivalents ​ $ (8,464,444) ​ $ 5,995,170 ​ Operating Activities During the year ended September 30, 2024, we used $68.8 million of cash in operating activities resulting primarily from our net loss of $75.4 million.
Cash Flows The following table summarizes our cash flows for each of the years presented: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year ended September 30, ​ ​ ​ ​ 2025 ​ ​ ​ 2024 Net cash used in operating activities ​ $ (51,829,437) ​ $ (68,793,858) Net cash provided by financing activities ​ ​ 44,984,984 ​ ​ 60,329,414 Net decrease in cash and cash equivalents ​ $ (6,844,453) ​ $ (8,464,444) ​ Operating Activities During the year ended September 30, 2025, we used $51.8 million of cash in operating activities resulting primarily from our net loss of $62.4 million.
In addition, through a Type A meeting and additional interactions with the FDA, we have identified the approaches needed to resolve the CMC comments in the CRL.
In addition, through a Type A meeting and additional interactions with the FDA, including Type C and Type D meetings, we identified the approaches needed to resolve the CMC comments in the CRL. We believe that we have addressed the open CMC items to help resolve these comments.
The primary endpoint is the mean change in BCVA from baseline to week 8. In November 2024, we reported that ONS-5010/LYTENAVA did not meet the pre-specified non-inferiority endpoint at week 8 set forth in the SPA.
In November 2024, we reported that ONS- 87 Table of Contents 5010/LYTENAVA did not meet the pre-specified non-inferiority endpoint at week 8 set forth in the SPA.
We do not believe our current 96 Table of Contents cash resources of $14.9 million, together with $1.7 million in net proceeds from the sale of shares of common stock under the BTIG ATM Offering since September 30, 2024, are sufficient to fund our operations through one year from the Form 10-K filing date as a result of the costs associated with the NORSE EIGHT clinical trial and the July 1, 2025 maturity date of the December 2022 Note, as amended in January 2024.
We do not believe our current cash resources of $8.1 million, together with $14.9 million in net proceeds from the sale of shares of common stock under the ATM Offering since September 30, 2025, are sufficient to fund our operations through one year from the Form 10-K filing date.
We have based this estimate on assumptions that may prove to be wrong, and we could utilize our available capital resources sooner than we expect. We will need to raise substantial additional capital in order to complete our planned ONS-5010/LYTENAVA development program.
We have based this estimate on assumptions that may prove to be wrong, and we could utilize our available capital resources sooner than we expect.
ONS-5010/LYTENAVA is the first and only authorized ophthalmic formulation of bevacizumab for use in treating wet AMD in the EU and UK.
ONS- 86 Table of Contents 5010/LYTENAVA is the first and only authorized ophthalmic formulation of bevacizumab for use in treating wet AMD in the EU and UK. Separately, in March 2022, we submitted a BLA to the FDA for ONS-5010/LYTENAVA for the treatment of wet AMD.
Subjects will be treated for three months, and the enrollment of subjects in the arm of the study receiving ONS-5010/LYTENAVA in vials has been completed. We have also received agreement from the FDA on three SPAs for three additional registration clinical trials for our ongoing Phase 3 program for ONS-5010/LYTENAVA.
We have also received agreement from the FDA on three SPAs for three additional registration clinical trials for our ongoing Phase 3 program for ONS-5010/LYTENAVA.
As of September 30, 2024, we had federal and state NOL carryforwards of $406.7 million and $242.5 million, respectively, that will begin to expire in 2030 and 2039, respectively. As of September 30, 2024, we had federal foreign tax credit carryforwards of $0.3 million available to reduce future tax liabilities, which begin to expire starting in 2023.
As of September 30, 2025, we had federal foreign tax credit carryforwards of $0.1 million available to reduce future tax liabilities, which begin to expire starting in 2024.
We may not be able to initiate commercialization of ONS-5010/LYTENAVA if, among other things, the FDA does not approve our BLA when we expect, or at all, or if we are not able to secure sufficient funding of our expected post-launch commercial costs.
We may not be able to initiate commercialization of ONS-5010/LYTENAVA if, among other things, the FDA does not approve our BLA when we expect, or at all, or if we are not able to secure sufficient funding of our expected post-launch commercial costs. 99 Table of Contents Our primary uses of capital are, and we expect will continue to be, compensation and related expenses, manufacturing and facility costs, external research and development services, laboratory and related supplies, legal and other regulatory expenses, and administrative and overhead costs.
We re-submitted the BLA to the FDA for ONS-5010/LYTENAVA on August 30, 2022, and in October 2022, we received confirmation from the FDA that our BLA had been accepted for filing with a goal date of August 29, 2023 for a review decision by the FDA.
In May 2022, we voluntarily withdrew our BLA to provide additional information requested by the FDA. We re-submitted the BLA to the FDA for ONS-5010/LYTENAVA in August 2022, and in October 2022, we received confirmation from the FDA that our BLA had been accepted for filing.
General and Administrative Expenses General and administrative expenses consist principally of salaries and related costs for personnel in executive, administrative, finance and legal functions, including stock-based compensation, travel expenses and recruiting expenses. Other general and administrative expenses include facility related costs, patent filing and prosecution costs and professional fees for business development, legal, auditing and tax services and insurance costs.
Selling, general and administrative expenses Selling, general and administrative expenses consist principally of distribution expenses, salaries and related costs for personnel in executive, administrative, finance and legal functions, including stock-based compensation, travel expenses and recruiting expenses.
Liquidity and Capital Resources We have not generated any revenue from product sales. Since inception, we have incurred net losses and negative cash flows from our operations.
Liquidity and Capital Resources We have one product, LYTENAVA, approved for commercialization in the EU and the UK, but we have not yet generated material revenue from its sales or from the sales of any other product. Since inception, we have incurred net losses and negative cash flows from our operations.
Change in Fair Value of Warrant Liability We issued warrants to purchase our common stock in conjunction with convertible senior secured notes issued pursuant to a certain Note and Warrant Purchase Agreement dated December 22, 2017, which are classified as liabilities and recorded at fair value.
In fiscal year 2024, we recorded income of $43.0 million, compared to $38.6 million in fiscal year 2024. We issued warrants to purchase our common stock in conjunction with convertible senior secured notes issued pursuant to a certain Note and Warrant Purchase Agreement dated December 22, 2017.
ASU 2023-07, which is applicable to entities with a single reportable segment and will primarily require enhanced disclosures about significant segment expenses and enhanced disclosures in interim periods.
ASU 2023-07, which is applicable to entities with a single reportable segment and will primarily require enhanced disclosures about significant segment expenses and enhanced disclosures in interim periods. We adopted ASU 2023-07 during fiscal year 2025, as the standard became effective for public entities for fiscal years beginning after December 15, 2023.
We anticipate incurring additional losses until such time, if ever, that we can generate significant sales of ONS-5010/LYTENAVA or any other product candidate we may develop.
Our net loss for the year ended September 30, 2025 was $62.4 million. We also had a net loss of $75.4 million for the year ended September 30, 2024. We anticipate incurring additional losses until such time, if ever, that we can generate significant sales of ONS-5010/LYTENAVA or any other product candidate we may develop.
We account for equity investments where we own a non-controlling interest, but have the ability to exercise significant influence, under the equity method of accounting. Interest income Interest income is earned from short term investments primarily money market investments. Interest Expense Interest expense consists of cash paid and non-cash interest expense related to our December 2022 Note.
Interest income The interest income is earned from short term investments primarily money market investments. Interest expense Interest expense consists of cash paid and non-cash interest expense related to our December 2022 Note and March 2025 Note.
In May 2024, the European Commission granted the Marketing Authorization for ONS-5010/LYTENAVA for the treatment of wet AMD in the EU. The decision applied automatically in all 27 EU Member States, and, within 30 days, also to Iceland, Norway and Liechtenstein.
The decision applied automatically in all 27 EU Member States, and, within 30 days, also to Iceland, Norway and Liechtenstein.
In November 2024 and December 2024, we sold 1,000,000 shares of common stock under the BTIG ATM Agreement generated $1.7 million in net proceeds after paying fees to BTIG and other issuance costs of $0.1 million.
Subsequent to September 30, 2025, we sold 10,227,166 shares of common stock under the BTIG ATM Agreement and generated $14.9 million in net proceeds after paying fees to BTIG and other issuance costs assessed as immaterial.
In addition, the Company has the right to convert all or any portion of the outstanding balance under the December 2022 Note into shares of common stock at the Conversion Price if certain conditions have been met at the time of conversion, including if at any time after the six-month anniversary of the closing date, the daily volume-weighted average price of the common stock on Nasdaq equals or exceeds $50.00 per share (subject to adjustments for stock splits and stock combinations) for a period of 30 consecutive trading days.
Furthermore, we retain the right to convert any portion of the outstanding balance under the March 2025 Note into shares of common stock at the Conversion Price, provided certain conditions are met at the time of conversion, including, but not limited to, the condition that the daily volume-weighted average price of our common stock on Nasdaq equals or exceeds $3.00 per share (subject to adjustments for stock splits and combinations) for a period of 30 consecutive trading days, and that the median daily dollar trading volume during the preceding 30 trading day period meets or exceeds $1,000,000.
The warrant related charges amounted to the difference between the fair value of the warrants and the net proceeds received from private placements that closed on March 18, 2024 and April 15, 2024. 94 Table of Contents Change in Fair Value of Warrant Liability We recognized income related to the decrease in the fair value of our common stock warrant liability in both fiscal years 2024 and 2023.
The warrant related charges amounted to the difference between the fair value of the warrants and the net proceeds received from private placements that closed on March 18, 2024 and April 15, 2024. Warrant inducement expenses During the year ended September 30, 2025, we recognized inducement charges associated with warrants exercised in the year.
However, the preliminary data from the trial demonstrated an improvement in vision and the presence of biologic activity, as well as a continued favorable safety profile for ONS-5010/LYTENAVA. Analysis of the data is ongoing as the month 3 data from NORSE EIGHT is being collected, which is expected to be available in January 2025.
In the intent-to-treat, or ITT, primary dataset, NORSE EIGHT demonstrated a mean +4.2 letter improvement in BCVA in the ONS-5010/LYTENAVA arm and +6.3 letter improvement in BCVA in the ranibizumab arm. However, the preliminary data from the trial demonstrated an improvement in vision and the presence of biologic activity, as well as a continued favorable safety profile for ONS-5010/LYTENAVA.
Our future funding requirements will be heavily determined by the resources needed to support the marketing and development of our lead product candidate and any other product candidates we may choose to pursue.
Our future funding requirements will primarily depend on the resources needed to support the commercialization and continued development of our lead product candidate, as well as any additional candidates we choose to advance.
We have also received $29.0 million pursuant to our collaboration and licensing agreements through such date. Our net loss for the year ended September 30, 2024 was $75.4 million. We also had a net loss of $59.0 million for the year ended September 30, 2023. We have not generated any revenue from product sales.
We have also received $29.0 million pursuant to our collaboration and licensing agreements through such date . We have not generated material revenue from the sales of any product. During the fiscal year 2025, we recognized revenues of $1.4 million from sales of LYTENAVA in Germany and the UK.
Overview We are a biopharmaceutical company working to launch the first ophthalmic formulation of bevacizumab approved by the European Commission in the European Union (EU), the Medicines and Healthcare products Regulatory Agency (MHRA) in the United Kingdom (UK) and the U.S. Food and Drug Administration (FDA), for use in retinal indications.
Overview We are a biopharmaceutical company that has developed ONS-5010/LYTENAVATM as the first ophthalmic formulation of bevacizumab approved by the European Commission in the European Union, or EU, and the Medicines and Healthcare products Regulatory Agency, or MHRA, in the United Kingdom, or UK, for use in adults for the treatment of wet age-related macular degeneration, or wet AMD.
See “Description of Indebtedness” and Note 7 in the Notes to Consolidated Financial Statements in this Annual Report on Form 10-K for additional detail. During the year ended September 30, 2024, an aggregate of principal and accrued interest totaling $11.3 million of the December 2022 Note was converted into 1,607,093 shares of our common stock.
During the year ended September 30, 2024, an aggregate of principal and accrued interest totaling $11.3 million of the December 2022 Note was converted into 1,607,093 shares of our common stock. On March 13, 2025, we used the proceeds from the March 2025 Note (as defined below) to pay off the December 2022 Note.
No shares of common stock were sold under the BTIG ATM Offering during the year ended September 30, 2024. During the year ended September 30, 2023, we sold 178,911 shares of common stock pursuant to the BTIG ATM Offering, generating $6.1 million in net proceeds after we paid fees to BTIG of $0.2 million.
During the year ended September 30, 2025, we sold 8,681,852 shares of common stock under the ATM Offering and generated approximately $13.5 million in net proceeds after paying fees to BTIG and other issuance costs of $0.4 million. No shares of common stock were sold under the ATM Offering.
If the Conversion Price is below $3.51 per share, the Company will be required to satisfy a conversion notice from the Lender in cash.
Furthermore, if the Conversion Price falls below $0.404 per share (subject to adjustments), we will be required to fulfill a conversion notice from Avondale in cash.
These increases were offset by a $4.7 million decrease in professional fees, which resulted from the discontinuation of U.S. commercial launch activities following the receipt of the CRL in August 2023. Loss on Equity Method Investment Loss on equity method investment represents our share of the loss from Beijing Syntone Biopharma Ltd, or Syntone JV.
These increases were partially offset by a $3.7 million reduction in professional fees and $0.4 million decrease in other selling, general and administration expenses driven by ongoing efforts to reduce expenditures unrelated to launch costs. Loss on equity method investment Loss on equity method investment represents our share of the loss from Beijing Syntone Biopharma Ltd, or Syntone JV.
The warrants are subject to re-measurement at each balance sheet date, and we recognize any change in fair value in our statements of operations. The gain recorded during the period was primarily due to the reduction in our stock price per share of common stock during the year.
The gain recorded during the period was primarily due to the reduction in our stock price per share of common stock during the year.
We are currently evaluating the impact that the adoption of ASU 2023-07 will have on its consolidated financial statements and disclosures. In December 2023, the FASB issued ASU 2023-09, Income Taxes (Topic 740): Improvements to Income Tax Disclosures .
For further details regarding the adoption and its impact, Note 3 in the Notes to Consolidated Financial Statements in this Annual Report on Form 10-K for additional detail. In December 2023, the FASB issued ASU 2023-09, Income Taxes (Topic 740): Improvements to Income Tax Disclosures .
We record the convertible promissory notes at fair value with changes in fair value recorded in the consolidated statements of operations. Warrant Related Expenses During the year ended September 30, 2024, we recognized charges associated with warrants issued during the period, which were categorized as liabilities.
The increase in the loss recognized from the change in fair value of promissory notes reflects an increase in the fair value of the convertible promissory notes, attributable to a lower conversion price on the March 2025 Note, higher volatility assumptions, and a reduced remaining term. 94 Table of Contents Warrant related expenses During the year ended September 30, 2024, we recognized charges associated with warrants issued during the period, which were categorized as liabilities.
This increase was primarily attributable to convertible promissory note maturity extension fees of $3.2 million associated with the December 2022 Note incurred during the year, in contrast to $2.5 million incurred in the prior year primarily related to the recognition of the original issue discount as interest expense on the December 2022 Note, as result of our adoption the fair value option for accounting purposes.
The decrease was primarily attributable to convertible promissory note maturity extension fees of $3.2 million associated with the unsecured promissory note issued on December 22, 2022, or the December 2022 Note, incurred in prior year.
Our initial goal is to launch directly or with a partner in the EU and UK, and, if approved, to launch directly in the United States as the first and only approved ophthalmic bevacizumab for the treatment of retina conditions, including wet age-related macular degeneration, or wet AMD.
If approved in the US., our goal is to also launch directly in the United States as the first and only approved ophthalmic bevacizumab for the treatment of wet AMD. In addition to Europe and the United States, we may seek approval to launc the product in other markets.
This income was attributed to a decline in the price of our common stock during those periods. In fiscal year 2024, we recorded income of $38.6 million, compared to $0.1 million in fiscal year 2023.
Gain from change in fair value of warrant liability We recognized income related to the decrease in the fair value of our common stock warrant liability in both fiscal years 2025 and 2024. This income was attributed to a decline in the price of our common stock during those periods.
Payments may be made by the Company (i) in cash, (ii) in shares of common stock, with the number of shares being equal to the portion of the applicable payment amount divided by the Conversion Price (as defined below), or (iii) a combination of cash and shares of common stock.
We reserve the right to make payments (i) in cash, (ii) in shares of common stock, calculated as the applicable payment amount divided by the Conversion Price, or (iii) a combination of both cash and shares of common stock. Any cash payments made by us, including prepayments or payments made at maturity, will incur an additional fee of 7.5%.
In the United States, 66.3% of retina physicians state off-label repackaged bevacizumab is their most commonly used first-line anti-VEGF (ASRS 2022 Membership Survey Presented at ASRS NY 2022). ​ On December 10, 2024, our board of directors approved a reduction of our workforce to reduce operating expenses and preserve capital.
In the United States, 66.3% of retina physicians state off-label repackaged bevacizumab is their most commonly used first-line anti-VEGF (ASRS 2022 Membership Survey Presented at ASRS NY 2022). ​ Going Concern Consideration Through September 30, 2025, we have funded substantially all of our operations with $612.0 million in proceeds from the sale and issuance of our equity and debt securities.

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