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What changed in Outlook Therapeutics, Inc.'s 10-K — 2023 vs 2024

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Paragraph-level year-over-year comparison of Outlook Therapeutics, Inc.'s 2023 and 2024 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 2024 report.

+826 added−643 removedSource: 10-K (2024-12-27) vs 10-K (2023-12-22)

Top changes in Outlook Therapeutics, Inc.'s 2024 10-K

826 paragraphs added · 643 removed · 502 edited across 5 sections

Item 1. Business

Business — how the company describes what it does

123 edited+137 added−45 removed123 unchanged
Biggest changeWe used approximately $0.9 million of the proceeds from the May 2020 private placement to Syntone to fund our initial capital contribution to the PRC joint venture, and are committed to make additional capital contributions to the PRC joint venture up to approximately $2.1 million which will be made within four years after the establishment date (April 2021) upon approval of the development plan contemplated in the license agreement or on such other terms as may be determined within such four-year period. 8 Table of Contents Selexis — Humira (ONS-3010), Avastin (ONS-5010 and ONS-1045) and Herceptin (ONS-1050) In October 2011, we entered into a research license agreement with Selexis, whereby we acquired a non-exclusive license to conduct research internally or in collaboration with third parties to develop recombinant proteins from cell lines created in mammalian cells using the Selexis expression technology, or the Selexis Technology.
Biggest changeWe used approximately $0.9 million of the proceeds from the May 2020 private placement to Syntone to fund our initial capital contribution to the PRC joint venture, and are committed to make additional capital contributions to the PRC joint venture up to approximately $2.1 million which will be made within four years after the establishment date (April 2021) upon approval of the development plan contemplated in the license agreement or on such other terms as may be determined within such four-year period.
HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act, or HITECH, and their implementing regulations, imposes requirements regarding the privacy and security of individually identifiable health information, including mandatory contractual terms, for covered entities, or certain healthcare providers, health plans, and healthcare clearinghouses, 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.
HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act, or HITECH, and their implementing regulations, imposes requirements regarding the privacy and security of individually identifiable health information, including mandatory contractual terms, for covered entities, or certain healthcare providers, health plans, and healthcare clearinghouses, 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 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; ● 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 14 Table of Contents ● 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, 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.
In August 2020, we reported positive proof-of-concept topline results for ONS-5010 as it achieved anticipated safety and efficacy expectations. In the analysis of treatment naïve patients who had a baseline visual acuity of 15 letters at Day 330. This subgroup was the relevant patient population for our pivotal clinical trial of ONS-5010 (NORSE TWO).
In August 2020, we reported positive proof-of-concept topline results for ONS-5010/LYTENAVA as it achieved anticipated safety and efficacy expectations. In the analysis of treatment naïve patients who had a baseline visual acuity of 15 letters at Day 330. This subgroup was the relevant patient population for our pivotal clinical trial of ONS-5010/LYTENAVA (NORSE TWO).
The NORSE TWO primary endpoint difference in proportion of subjects gaining at least 15 letters in Best Corrected Visual Acuity, or BCVA, score was met and was both highly statistically significant and clinically relevant. For a discussion of NORSE TWO, please see “Our Product Candidate Portfolio— ONS-5010 — Bevacizumab for Ophthalmic Use—Clinical Development Status —NORSE TWO”.
The NORSE TWO primary endpoint difference in proportion of subjects gaining at least 15 letters in Best Corrected Visual Acuity, or BCVA, score was met and was both highly statistically significant and clinically relevant. For a discussion of NORSE TWO, please see “Our Product Candidate Portfolio— ONS-5010/LYTENAVA — Bevacizumab for Ophthalmic Use—Clinical Development Status —NORSE TWO”.
We can provide no assurance that developments by others will not render our technology obsolete, noncompetitive or harm our development strategy, that we will be able to keep pace with new technological developments, that our technology will be able to supplant established products and methodologies in the therapeutic areas that are targeted by us or that we will be able to enter into a strategic partnership arrangement for ONS-5010.
We can provide no assurance that developments by others will not render our technology obsolete, noncompetitive or harm our development strategy, that we will be able to keep pace with new technological developments, that our technology will be able to supplant established products and methodologies in the therapeutic areas that are targeted by us or that we will be able to enter into a strategic partnership arrangement for ONS-5010/LYTENAVA.
Our registration plan for wet AMD, the initial indication planned for ONS-5010, 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. 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.
Annual revenue (worldwide) for anti-VEGF therapies was estimated to be $13.1 billion in 2020 (Triangulation of Global Data, Market Scope and Investor Forecasts (2020)). We expect to strategically price ONS-5010 to make it a lower cost alternative to biosimilars and premium branded products, while higher than off-label compounds.
Annual revenue (worldwide) for anti-VEGF therapies was estimated to be $13.1 billion in 2020 (Triangulation of Global Data, Market Scope and Investor Forecasts (2020)). We expect to strategically price ONS-5010/LYTENAVA to make it a lower cost alternative to biosimilars and premium branded products, while higher than off-label compounds.
The topline results reported from NORSE TWO in August 2021 showed that ONS-5010 met the primary and key secondary endpoint for efficacy with clinically impactful change observed for treated patients. The NORSE TWO primary endpoint difference in proportion of subjects gaining at least 15 letters in BCVA score was met and was both highly statistically significant and clinically relevant.
The topline results reported from NORSE TWO in August 2021 showed that ONS-5010/LYTENAVA met the primary and key secondary endpoint for efficacy with clinically impactful change observed for treated patients. The NORSE TWO primary endpoint difference in proportion of subjects gaining at least 15 letters in BCVA score was met and was both highly statistically significant and clinically relevant.
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.
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.
The study design for our clinical program to evaluate ONS-5010 as an ophthalmic formulation of bevacizumab was reviewed at an end of Phase 2 meeting with the FDA in April 2018, and we filed our investigational new drug application, or IND, with the FDA in the first quarter of calendar 2019.
The study design for our clinical program to evaluate ONS-5010/LYTENAVA as an ophthalmic formulation of bevacizumab was reviewed at an end of Phase 2 meeting with the FDA in April 2018, and we filed our investigational new drug application, or IND, with the FDA in the first quarter of calendar 2019.
The agreements reached with the FDA on these SPAs cover the protocols for NORSE FOUR, a registration clinical trial evaluating ONS-5010 to treat BRVO, and NORSE FIVE and NORSE SIX, two registration clinical trials evaluating ONS-5010 to treat DME. We intend to initiate these studies following the anticipated FDA approval of our BLA 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. We intend to initiate these studies following the anticipated FDA approval of our BLA for wet AMD.
The primary endpoint for the study was the difference in proportion of subjects gaining 15 letters of BCVA at Day 330 for ONS-5010 dosed on a monthly basis compared to ranibizumab dosed using the PIER alternative dosing regimen. We reported topline results for NORSE TWO in August 2021.
The primary endpoint for the study was the difference in proportion of subjects gaining 15 letters of BCVA at Day 330 for ONS-5010/LYTENAVA dosed on a monthly basis compared to ranibizumab dosed using the PIER alternative dosing regimen. We reported topline results for NORSE TWO in August 2021.
Clinical Development Status The study design for our Phase 3 clinical program to evaluate ONS-5010 as an ophthalmic formulation of bevacizumab was reviewed with the FDA at an end of Phase 2 meeting in April 2018, and we filed our IND with the FDA in the first quarter of calendar 2019.
Clinical Development Status ​ The study design for our Phase 3 clinical program to evaluate ONS-5010/LYTENAVA as an ophthalmic formulation of bevacizumab was reviewed with the FDA at an end of Phase 2 meeting in April 2018, and we filed our IND with the FDA in the first quarter of calendar 2019.
After reviewing our BLA for ONS-5010, the FDA issued a CRL indicating that 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.
After reviewing our BLA for ONS-5010/LYTENAVA, the FDA issued a CRL indicating that 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.
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.
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.
The primary endpoint for the study was the difference in proportion of subjects gaining 15 letters of BCVA at Day 330 for ONS-5010 dosed on a monthly basis compared to ranibizumab dosed using the PIER alternative dosing regimen of three monthly doses followed by quarterly dosing.
The primary endpoint for the study was the difference in proportion of subjects gaining 15 letters of BCVA at Day 330 for ONS-5010/LYTENAVA dosed on a monthly basis compared to ranibizumab dosed using the PIER alternative dosing regimen of three monthly doses followed by quarterly dosing.
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.
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.
We currently own all of the development and commercialization rights to ONS-5010 and have licensed rights only to our joint venture in the People’s Republic of China, or PRC, for the greater China market (see “—Collaboration and License Agreements—Syntone-Private Placement and PRC Joint Venture”).
We currently own all of the development and commercialization rights to ONS-5010/LYTENAVA and have licensed rights only to our joint venture in the People’s Republic of China, or PRC, for the greater China market (see “-Collaboration and License Agreements-Syntone-Private Placement and PRC Joint Venture”).
We re-submitted the BLA to the FDA for ONS-5010 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.
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.
Additionally, in a key secondary endpoint for the relevant patient population, the ONS-5010 patients achieved a mean improvement in BCVA of 8.3 letters. NORSE TWO NORSE TWO was a masked, randomized, pivotal Phase 3 clinical trial evaluating ONS-5010 against ranibizumab for wet AMD.
Additionally, in a key secondary endpoint for the relevant patient population, the ONS-5010/LYTENAVA patients achieved a mean improvement in BCVA of 8.3 letters . NORSE TWO NORSE TWO was a masked, randomized, pivotal Phase 3 clinical trial evaluating ONS-5010/LYTENAVA against ranibizumab for wet AMD.
However, although multiple branded drugs have been approved for these indications (e.g., LUCENTIS, EYLEA, BEOVU, SUSVIMO and VABYSMO), they are very expensive. The recently approved biosimilar versions of LUCENTIS 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 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.
We exercised this option in April 2013 and entered into three commercial license agreements with Selexis for ONS-1045 (which covers ONS-5010), and two of our biosimilar product candidates, ONS-3010 and ONS-1050 (which are no longer in active clinical development).
We exercised this option in April 2013 and entered into three commercial license agreements with Selexis for ONS-1045 (which covers ONS-5010/LYTENAVA), and two of our biosimilar product candidates, ONS-3010 and ONS-1050 (which are no longer in active clinical development).
A total of 120 patients are expected to be enrolled in the study with 60 patients receiving ONS-5010 packaged in vials and 60 patients receiving ONS packaged in a pre-filled syringe. Subjects will be treated for three months and the enrollment of subjects in the arm of the study receiving ONS-5010 in vials has been completed.
A total of 120 patients are expected to be enrolled in the study with 60 patients receiving ONS-5010/LYTENAVA packaged in vials and 60 patients receiving ONS packaged in a pre-filled syringe. 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.
A total of 227 primarily treatment naïve patients were enrolled at 39 clinical trial sites in the United States. Patients enrolled in the study were randomized to either ONS-5010 or ranibizumab arms and were treated for 11 months.
A total of 227 primarily treatment naïve patients were enrolled at 39 clinical trial sites in the United States. Patients enrolled in the study were randomized to either ONS-5010/LYTENAVA or ranibizumab arms and were treated for 11 months.
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, 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, 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.
In March 2021 we reported that the results from NORSE THREE provided a positive safety profile for ONS-5010. NORSE SEVEN NORSE SEVEN was initiated to support our ongoing development program for delivering ONS-5010 using a pre-filled syringe.
In March 2021 we reported that the results from NORSE THREE provided a positive safety profile for ONS-5010/LYTENAVA. NORSE SEVEN NORSE SEVEN was initiated to support our ongoing development program for delivering ONS-5010/LYTENAVA using a pre-filled syringe.
The principal purposes of our equity and cash incentive plans are to attract, retain and reward personnel through the granting of stock-based and cash-based compensation awards, in order to increase stockholder value and the success of our company by motivating such individuals to perform to the best of their abilities and achieve our objectives. 21 Table of Contents Corporate Information We initially incorporated in January 2010 in New Jersey as Oncobiologics, Inc., and in October 2015, we reincorporated in Delaware by merging with and into a Delaware corporation.
The principal purposes of our equity and cash incentive plans are to attract, retain and reward personnel through the granting of stock-based and cash-based compensation awards, in order to increase stockholder value and the success of our company by motivating such individuals to perform to the best of their abilities and achieve our objectives. 26 Table of Contents Corporate Information We initially incorporated in January 2010 in New Jersey as Oncobiologics, Inc., and in October 2015, we reincorporated in Delaware by merging with and into a Delaware corporation.
A total of 61 treatment naïve and previously treated patients were enrolled in the study at nine sites in Australia and randomized onto treatment arms of ONS-5010 or ranibizumab.
A total of 61 treatment naïve and previously treated patients were enrolled in the study at nine sites in Australia and randomized onto treatment arms of ONS-5010/LYTENAVA or ranibizumab.
Results were also positive for the remaining NORSE TWO secondary endpoints with 56.5% (p = 0.0016) of ONS-5010 subjects gaining ≥ 10 letters of vision and 68.5% (p = 0.0116) of ONS-5010 subjects gaining ≥ 5 letters of vision. 5 Table of Contents ​ ​ NORSE THREE NORSE THREE was an open-label safety study we conducted to ensure the adequate number of safety exposures to ONS-5010 were available for the initial ONS-5010 BLA submission with the FDA.
Results were also positive for the remaining NORSE TWO secondary endpoints with 56.5% (p = 0.0016) of ONS-5010/LYTENAVA subjects gaining ≥ 10 letters of vision and 68.5% (p = 0.0116) of ONS-5010/LYTENAVA subjects gaining ≥ 5 letters of vision . 6 Table of Contents ​ ​ NORSE THREE 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.
We seek to protect our proprietary technologies by, among other methods, evaluating relevant patents, establishing defensive positions, monitoring E.U. 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 U.S. and international patent applications on technologies, inventions and improvements that are important to our business.
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 18 Table of Contents 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, 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.
It is a three month study designed to compare the safety of ophthalmic bevacizumab in vials versus pre-filled 6 Table of Contents 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 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.
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.
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.
Our sixth PCT application was nationalized in August 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 fifth PCT application was nationalized in August 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.
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’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 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.
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)).
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)).
NORSE TWO is our pivotal Phase 3 clinical trial comparing ONS-5010 to ranibizumab (LUCENTIS) that reported highly statistically significant topline results in August 2021. NORSE THREE is an open-label safety study conducted to ensure the adequate number of safety exposures to ONS-5010 were available for the ONS-5010 BLA submission with the FDA.
NORSE TWO was our pivotal Phase 3 clinical trial comparing ONS-5010/LYTENAVA to ranibizumab (LUCENTIS) that reported highly statistically significant topline results in August 2021. NORSE THREE was an open-label safety study conducted to ensure the adequate number of safety exposures to ONS-5010/LYTENAVA were available for the ONS-5010/LYTENAVA BLA submission with the FDA.
Syntone – Private Placement and PRC Joint Venture In May 2020, we entered into a stock purchase agreement with Syntone Ventures LLC, or Syntone, pursuant to which we sold and issued, in a private placement in June 2020, 16,000,000 shares of our common stock at a purchase price of $1.00 per share, for aggregate gross proceeds of $16.0 million.
Syntone – Private Placement and PRC Joint Venture In May 2020, we entered into a stock purchase agreement with Syntone Ventures LLC, or Syntone, pursuant to which we sold and issued, in a private placement in June 2020, 800,000 shares of our common stock at a purchase price of $20.00 per share, for aggregate gross proceeds of $16.0 million.
The initiation of our Phase 3 clinical program for ONS-5010 in fiscal 2019 triggered a CHF 65,000 (approximately $0.1 million) milestone payment to Selexis under the commercial license agreement, which we paid in November 2019. As of September 30, 2023, we have paid Selexis an aggregate of approximately $0.4 million under the commercial license agreements.
The initiation of our Phase 3 clinical program for ONS-5010/LYTENAVA in fiscal 2019 triggered a CHF 65,000 (approximately $0.1 million) milestone payment to Selexis under the commercial license agreement, which we paid in November 2019. As of September 30, 2024, we have paid Selexis an aggregate of approximately $0.4 million under the commercial license agreements.
These so-called Phase 4 studies may be made a condition to approval of the BLA. Concurrent with clinical trials, companies may complete additional animal studies and develop additional information about the biological characteristics of the product candidate and must finalize a process for manufacturing the 15 Table of Contents product in commercial quantities in accordance with cGMP requirements.
These so-called Phase 4 studies may be made a condition to approval of the BLA. Concurrent with clinical trials, companies may complete additional animal studies and develop additional information about the biological characteristics of the product candidate and must finalize a process for manufacturing the product in commercial quantities in accordance with cGMP requirements.
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.
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.
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.
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 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 = 0.0043). A mean change of 11.2 letters in BCVA score was observed with ONS-5010, 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 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.
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.
Since the advent of anti-VEGF therapy, it has become the standard of care treatment option within the retina community, globally. Wet AMD is a significant disease worldwide, with an estimated prevalence of over 2.9 million patients diagnosed in the United States, European countries and Japan alone in 2020 (GlobalData).
Anti-VEGF injection therapy blocks this growth. Since the advent of anti-VEGF therapy, it has become the standard of care treatment option within the retina community, globally. Wet AMD is a significant disease worldwide, with an estimated prevalence of over 2.9 million patients diagnosed in the United States, European countries and Japan alone in 2020 (GlobalData).
We believe in the value of having an affordable, FDA and EMA-approved option for patients that is safe, effective, and manufactured under proper guidance. Our commercial strategy for ONS-5010 includes providing an on-label bevacizumab as a first line option for treating retinal diseases.
We believe in the value of having an affordable, FDA and European Commission-approved option for patients that is safe, effective, and manufactured under proper guidance. Our commercial strategy for ONS-5010/LYTENAVA includes providing an on-label bevacizumab as a first line option for treating retinal diseases.
The loss of any of these suppliers, or any future single source suppliers, could harm our business. 11 Table of Contents Competition Competition in the area of pharmaceutical research and development is extensive and significantly depends upon multiple scientific and technological factors.
The loss of any of these suppliers, or any future single source suppliers, could harm our business. Competition Competition in the area of pharmaceutical research and development is extensive and significantly depends upon multiple scientific and technological factors.
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.
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.
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.
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.
The topline results reported from NORSE TWO in August 2021 showed that ONS-5010 met the primary and key secondary endpoint for efficacy with clinically impactful change observed for treated patients.
The topline results reported from NORSE TWO in August 2021 showed that ONS-5010/LYTENAVA met the primary and key secondary endpoints for efficacy with clinically impactful change observed for treated patients.
To date, a number of biosimilars 17 Table of Contents have been licensed under the BPCIA, and numerous biosimilars have been approved in Europe. The FDA has issued several guidance documents outlining an approach to review and approval of biosimilars.
To date, a number of biosimilars have been licensed under the BPCIA, and numerous biosimilars have been approved in Europe. The FDA has issued several guidance documents outlining an approach to review and approval of biosimilars.
Because there are no approved bevacizumab products for the treatment of retinal diseases in the United States and other major markets, we submitted a standard BLA, and are not using the biosimilar drug development pathway that would be required if Avastin were an approved drug for the targeted diseases.
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.
We believe that ONS-5010 has potential competitive advantages due to the familiarity of physicians in using off-label Avastin. We also believe that an affordable, FDA and EMA-approved bevacizumab option, that is safe, effective, and manufactured under proper guidance will garner strong market uptake and patient access to therapy.
We believe that ONS-5010/LYTENAVA has potential competitive advantages due to the familiarity of physicians in using off-label Avastin. We also believe that an affordable, FDA and European Commission-approved ophthalmic bevacizumab option, that is safe, effective, and manufactured under proper guidance will garner strong market uptake and patient access to therapy.
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 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, 9 Table of Contents commercialization and manufacture of ONS-5010/LYTENAVA in the greater China market, which includes Hong Kong, Taiwan and Macau.
Selexis also granted us a non-transferrable option to obtain a perpetual, non-exclusive, worldwide commercial license under the Selexis Technology to manufacture, or have manufactured, a recombinant protein produced by a cell line developed using the Selexis Technology for clinical testing and commercial sale.
Selexis In October 2011, Selexis granted us a non-transferrable option to obtain a perpetual, non-exclusive, worldwide commercial license under the Selexis Technology to manufacture, or have manufactured, a recombinant protein produced by a cell line developed using the Selexis Technology for clinical testing and commercial sale.
The results were also statistically significant in the secondary PP dataset (p = 0.05) with a mean change with ONS-5010 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.
NORSE THREE is an open-label safety study we conducted to ensure the adequate 1 Table of Contents number of safety exposures to ONS-5010 were available for the initial ONS-5010 BLA submission with the FDA. In March 2021, we reported that the results from NORSE THREE showed a positive safety profile for ONS-5010.
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.
We have entered into a strategic commercialization agreement for the future distribution of ONS-5010, which is intended to provide us with the leverage and capabilities of a large biopharmaceutical company, if approved.
We have entered into a strategic commercialization agreement for the distribution of ONS-5010/LYTENAVA, which is intended to provide us with the leverage and capabilities of a large biopharmaceutical company.
If approved, we believe ONS-5010 has potential to mitigate risks associated with off-label repackaging of bevacizumab including, but not limited to, variability in potency, safety and sterility adverse events and syringe-related 3 Table of Contents adverse events. DME is caused by a complication of diabetes called diabetic retinopathy.
We believe ONS-5010/LYTENAVA has potential to mitigate risks associated with off-label repackaging of bevacizumab including, but not limited to, variability in potency, safety and sterility adverse events and syringe-related adverse events . DME is caused by a complication of diabetes called diabetic retinopathy.
Additionally, on March 11, 2021, President Biden signed the American Rescue Plan Act of 2021 into law, which eliminates the statutory Medicaid drug rebate cap, currently set at 100% of a drug’s average manufacturer price, for single source and innovator multiple source drugs, beginning January 1, 2024.
Additionally, on March 11, 2021, President Biden signed the American Rescue Plan Act of 2021 into law, which eliminated the statutory Medicaid drug rebate cap, previously set at 100% of a drug’s average manufacturer price, for single source and innovator multiple source drugs, effective January 1, 2024.
Additionally, on June 17, 2021 the U.S. Supreme Court dismissed a challenge on procedural grounds that argued the Affordable Care Act is unconstitutional in its entirety because the “individual mandate” was repealed by Congress. . In addition, there have been a number of health reform initiatives by the Biden administration that have impacted the Affordable Care Act.
Supreme Court dismissed a challenge on procedural grounds that argued the Affordable Care Act is unconstitutional in its entirety because the “individual mandate” was repealed by Congress. In addition, there have been a number of health reform initiatives by the Biden administration that have impacted the Affordable Care Act.
We intend to leverage their collective experience to further the development of, and execute an optimal commercial strategy for, ONS-5010, including potentially licensing rights to ONS-5010 to a strategic partner outside the United States. ● Engaging with regulatory agencies to establish clear guidelines for potential approval.
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.
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.
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.
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, as well as additional requested CMC data indicated in the CRL to approve ONS-5010 for use in wet AMD.
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.
In August 2020, we reported achieving the anticipated safety and efficacy and positive proof-of-concept topline results from NORSE ONE, a clinical experience study. NORSE TWO is our pivotal Phase 3 clinical trial comparing ONS-5010 (bevacizumab-vikg) to ranibizumab (LUCENTIS).
In August 2020, we reported achieving the anticipated safety and efficacy proof-of-concept results from NORSE ONE, a clinical experience study. NORSE TWO was our pivotal Phase 3 clinical trial comparing ONS-5010/LYTENAVA to ranibizumab (LUCENTIS).
Decreases in third-party reimbursement for our product candidates or a decision by a third-party payor to not cover our product candidates could reduce physician utilization of our products and have a material adverse effect on our sales, results of operations and financial condition.
Decreases in third-party reimbursement for our product candidates or a decision by a third-party payor to not cover our product candidates could reduce physician utilization of our products and have a material adverse effect on our sales, results of operations and financial condition. ​ In Europe, pricing and reimbursement schemes vary widely from country to country.
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. Anti-VEGF injection therapy blocks this growth.
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.
Although bevacizumab is not currently FDA-approved for use in treating wet AMD, in the United States, approximately 66.3% of new patient starts are off-label repackaged bevacizumab (ASRS 2022 Membership Survey Presented at ASRS NY 2022). Similarly, despite not being EMA-approved, bevacizumab is commonly utilized in the treatment of wet AMD in Europe.
Although bevacizumab is not currently FDA-approved for use in treating wet AMD, in the United States, approximately 66.3% of new patient starts are off-label repackaged bevacizumab (ASRS 2022 Membership Survey Presented at ASRS NY 2022).
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 BLA. The FDA is expected to respond to the SPA in early February 2024.
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.
If approved, we believe that LYTENAVA (bevacizumab-vikg) will be entitled to 12 years of regulatory exclusivity granted in the United States against biosimilar competition, and up to 10 years of market exclusivity in Europe. ​ For many years, anti-VEGF therapy has been the standard of care for many ophthalmic diseases, including wet AMD, DME and BRVO.
If approved by the FDA, we believe that ONS-5010/LYTENAVA will be entitled to 12 years of regulatory exclusivity granted in the United States against biosimilar competition. ​ For many years, anti-VEGF therapy has been the standard of care for many ophthalmic diseases, including wet AMD, DME and BRVO.
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.
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.
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.
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.
Our Product Candidate Portfolio We are actively developing ONS-5010 (LYTENAVA (bevacizumab-vikg)) for use in the treatment of retina diseases such as wet AMD, 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 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 .
As of October 1, 2023, we own three U.S. patents, sixteen foreign patents, one pending U.S. non-provisional application, and 18 pending international applications that were nationalized from seven Patent Cooperation Treaty, or PCT, applications, which relate to formulations developed for ONS-3010 and ONS-5010/ONS-1045, methods of antibody purification, methods for purifying antibodies to separate isoforms, methods of use, methods of reducing high molecular weight species, and modulating afucosylated species as well as efficiently determining the amino acid sequence of antibodies.
As of September 30, 2024, we own three U.S. patents, eighteen foreign patents, and two pending international applications that were nationalized from six Patent Cooperation Treaty, or PCT, applications, which relate to formulations developed for our legacy biosimilar program ONS-3010 and ONS-5010/ONS-1045, methods of antibody purification, methods for purifying antibodies to separate isoforms, methods of use, methods of reducing high molecular weight species, and modulating afucosylated species as well as efficiently determining the amino acid sequence of antibodies.
In most countries, including the United States, the patent term is generally 20 years from the earliest date of filing a non-provisional patent application in the applicable country.
The term of individual patents depends upon the legal term of the patents in countries in which they are obtained. In most countries, including the United States, the patent term is generally 20 years from the earliest date of filing a non-provisional patent application in the applicable country.
We have continued our approach to work closely with regulatory authorities to develop and conduct clinical trials that we believe will appropriately support approval of our product candidates if our clinical trials are successful. ● Leveraging the expertise of large partners in the biopharma industry to support launch of ONS-5010, if approved.
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.
If our operations are found to be in violation of any of such laws or any other governmental regulations that apply to us, we may be subject to significant penalties, including, without limitation, civil, criminal and administrative penalties, damages, fines, disgorgement, additional reporting requirements and oversight if we become subject to a corporate integrity agreement or similar agreement to resolve allegations of non-compliance with these laws, the curtailment or restructuring of our operations, exclusion from participation in federal and state healthcare programs and individual imprisonment, any of which could adversely affect our ability to operate our business and our financial results.
If our operations are found to be in violation of any of such laws or any other governmental regulations that apply to us, we may be subject to significant penalties, including, without limitation, civil, criminal and administrative penalties, damages, fines, disgorgement, additional reporting requirements and oversight if we become subject to a corporate integrity agreement or similar agreement to resolve allegations of non-compliance with these laws, the curtailment or restructuring of our operations, exclusion from participation in federal and state healthcare programs and individual imprisonment, any of which could adversely affect our ability to operate our business and our financial results. 18 Table of Contents Healthcare Reform In the United States and some foreign jurisdictions there have been, and we expect there will continue to be, several legislative and regulatory changes and proposed reforms of the healthcare system to contain costs, improve quality, and expand access to care.
In addition, more than 200,000 new cases are diagnosed annually in North America. Similary, it is estimated that the prevalence of wet AMD in Europe is approximately 1.7 million people.
In addition, more than 200,000 new cases are diagnosed annually in North America. Similary, it is estimated that the prevalence of wet AMD in Europe is approximately 1.7 million people. Globally, the incidence and prevalence of wet AMD is projected to increase significantly in the future due to an aging population.

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Item 1A. Risk Factors

Risk Factors — what could go wrong, per management

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Biggest changeWe currently estimate that we could potentially begin generating revenue from product sales as early as late 2025, but this depends heavily on our success in many areas, including but not limited to: ● completing clinical development of ONS-5010 for the treatment of wet AMD and the other targeted indications, and any other product candidates we may develop in the future; ● obtaining regulatory and marketing approvals for ONS-5010 and any other product candidates for which we or our partners complete clinical trials; ● retaining our manufacturing partner for ONS-5010 and any approved product candidates to support clinical development, regulatory requirements and the market demand for any such approved product candidates; ● launching and commercializing ONS-5010 and any other product candidates for which we or our partners obtain regulatory and marketing approval; ● obtaining third-party coverage and adequate reimbursements for our products; ● obtaining market acceptance of ONS-5010 and any other product candidates for which we obtain regulatory and marketing approval as viable treatment options; ● negotiating favorable terms in any collaboration, licensing or other arrangements into which we may enter; 23 Table of Contents ● maintaining, protecting and expanding our portfolio of intellectual property rights, including patents, trade secrets and know-how; and ● attracting, hiring and retaining qualified personnel.
Biggest changeWe currently estimate that we could potentially begin generating revenue from product sales in Europe as early as the first half of calendar 2025, but this depends heavily on our success in many areas, including but not limited to: ● Securing capital sufficient to fund our commercialization efforts; ● launching and commercializing ONS-5010/LYTENAVA and any other product candidates for which we or our partners obtain regulatory and marketing approval; ● maintaining and obtaining regulatory and marketing approvals for ONS-5010/LYTENAVA and any other product candidates for which we or our partners complete clinical trials; ● retaining our manufacturing partner for ONS-5010/LYTENAVA and any approved product candidates to support clinical development, regulatory requirements and the market demand for any such approved product candidates; ● obtaining third-party coverage and adequate reimbursements of ONS-5010/LYTENAVA and any other product candidates, if approved ; ● obtaining market acceptance of ONS-5010/LYTENAVA and any other product candidates for which we obtain regulatory and marketing approval as viable treatment options; 28 Table of Contents ● establishing or demonstrating in the medical community the safety and efficacy of ONS-5010/LYTENAVA and its potential advantages over and side effects compared to existing products used to treat wet AMD; ● negotiating favorable terms in any collaboration, licensing or other arrangements into which we may enter; ● maintaining, protecting and expanding our portfolio of intellectual property rights, including patents, trade secrets and know-how; ● attracting, hiring and retaining qualified personnel; and ● completing clinical development of ONS-5010/LYTENAVA for the treatment of wet AMD in the United States and the other targeted indications, and any other product candidates we may develop in the future.
As such, our current and future manufacturing partners will be subject to continual review and inspections to assess compliance with cGMP and adherence to commitments made in any non-disclosure agreement, BLA or marketing authorization application.
As such, our current and future manufacturing partners will be subject to continual review and inspections to assess compliance with cGMP and adherence to commitments made in any non-disclosure agreement, marketing authorization, BLA or marketing authorization application.
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.
If our clinical candidates are discontinued or their clinical development is further delayed, if the launch of new indications for our marketed products or new product candidates is delayed or does not occur, or if such products are launched and the launch is unsuccessful or the product is subsequently recalled or marketing approval is rescinded, we may have to absorb one hundred percent of related overhead costs and inefficiencies, as well as similar costs of third-party contract manufacturers performing services for us.
If our product candidates are discontinued or their clinical development is further delayed, if the launch of new indications for our marketed products or new product candidates is delayed or does not occur, or if such products are launched and the launch is unsuccessful or the product is subsequently recalled or marketing approval is rescinded, we may have to absorb one hundred percent of related overhead costs and inefficiencies, as well as similar costs of third-party contract manufacturers performing services for us.
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; ● 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; 35 Table of Contents ● 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; 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 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; 61 Table of Contents ● 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 laws that require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government or otherwise restrict payments that may be made to healthcare providers and other potential referral sources; state laws that require drug manufacturers to report information related to payments and other transfers of value to physicians and other healthcare providers or marketing expenditures or drug pricing; state 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; ● 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 complaint alleges, among other things, that we violated Sections 10(b) and 20(a) of the Exchange Act and SEC Rule 10b-5 by failing to disclose that there was an alleged lack of evidence supporting ONS-5010 as a treatment for wet AMD and that we and/or our manufacturing partner had deficient CMC controls for ONS-5010, which remained unresolved at the time our BLA was re-submitted to the FDA and, as a result, the FDA was unlikely to approve our BLA, and that our stock price dropped when such information was disclosed.
The complaint alleges, among other things, that we violated Sections 10(b) and 20(a) of the Exchange Act and SEC Rule 10b-5 by failing to disclose that there was an alleged lack of evidence supporting ONS-5010/LYTENAVA as a treatment for wet AMD and that we and/or our manufacturing partner had deficient CMC controls for ONS-5010/LYTENAVA, which remained unresolved at the time our BLA was re-submitted to the FDA and, as a result, the FDA was unlikely to approve our BLA, and that our stock price dropped when such information was disclosed.
It is possible that as we test a product candidate in larger, longer and more extensive clinical trials including for additional indications, or as the use of ONS-5010 or any future product candidate becomes more widespread following regulatory approval, illnesses, injuries, discomforts and other adverse events that were observed in earlier trials, as well as conditions that did not occur or went undetected in previous trials, will be reported by patients.
It is possible that as we test a product candidate in larger, longer and more extensive clinical trials including for additional indications, or as the use of ONS-5010/LYTENAVA or any future product candidate becomes more widespread following regulatory approval, illnesses, injuries, discomforts and other adverse events that were observed in earlier trials, as well as conditions that did not occur or went undetected in previous trials, will be reported by patients.
If the market for ONS-5010 or any other product candidates we may develop in the future, or our share of that market, is not as large as we expect, the number of indications approved by regulatory authorities is narrower than we expect or the target population for treatment is narrowed by competition, physician choice or treatment guidelines, we may not generate significant revenue from sales of such products to become profitable.
If the market for ONS-5010/LYTENAVA or any other product candidates we may develop in the future, or our share of that market, is not as large as we expect, the number of indications approved by regulatory authorities is narrower than we expect or the target population for treatment is narrowed by competition, physician choice or treatment guidelines, we may not generate significant revenue from sales of such products to become profitable.
Moreover, if ONS-5010 or any future product candidate is associated with undesirable side effects in clinical trials or have characteristics that are unexpected, we may elect to abandon or limit its development to more narrow uses or subpopulations in which the undesirable side effects or other characteristics are less prevalent, less severe or more acceptable from a risk-benefit perspective, which may limit the commercial expectations, if approved.
Moreover, if ONS-5010/LYTENAVA or any future product candidate is associated with undesirable side effects in clinical trials or have characteristics that are unexpected, we may elect to abandon or limit its development to more narrow uses or subpopulations in which the undesirable side effects or other characteristics are less prevalent, less severe or more acceptable from a risk-benefit perspective, which may limit the commercial expectations, if approved.
Even if ONS-5010 or any other product candidate we may develop in the future displays an equivalent or more favorable efficacy and safety profile in preclinical and clinical trials, market acceptance of the product candidate will not be fully known until after it is launched and may be negatively affected by a potential poor safety experience and the track record of other product candidates.
Even if ONS-5010/LYTENAVA or any other product candidate we may develop in the future displays an equivalent or more favorable efficacy and safety profile in preclinical and clinical trials, market acceptance of ONS-5010/LYTENAVA or any other product candidate will not be fully known until after it is launched and may be negatively affected by a potential poor safety experience and the track record of other product candidates.
Although we believe that there are alternate sources for these services, we cannot assure you that identifying and establishing new relationships would not result in significant delay in the development of ONS-5010. Additionally, we may not be able to enter into arrangements with alternative vendors on commercially reasonable terms, or at all.
Although we believe that there are alternate sources for these services, we cannot assure you that identifying and establishing new relationships would not result in significant delay in the development of ONS-5010/LYTENAVA. Additionally, we may not be able to enter into arrangements with alternative vendors on commercially reasonable terms, or at all.
If we secure development funds for ONS-5010 or any future product candidate through entering into collaborations, strategic alliances or licensing arrangements with third parties, we may have to relinquish additional valuable rights to our technologies, future revenue streams, research programs or product candidates or to grant licenses on terms that may not be favorable to us.
If we secure development funds for ONS-5010/LYTENAVA or any future product candidate through entering into collaborations, strategic alliances or licensing arrangements with third parties, we may have to relinquish additional valuable rights to our technologies, future revenue streams, research programs or product candidates or to grant licenses on terms that may not be favorable to us.
The clinical development, manufacturing, labeling, packaging, storage, recordkeeping, advertising, promotion, export, import, marketing, distribution, adverse event reporting, including the submission of safety and other post-marketing information and reports, and other possible activities relating to ONS-5010, as well as any other product candidate that we may develop in the future, are subject to extensive regulation.
The clinical development, manufacturing, labeling, packaging, storage, recordkeeping, advertising, promotion, export, import, marketing, distribution, adverse event reporting, including the submission of safety and other post-marketing information and reports, and other possible activities relating to ONS-5010/LYTENAVA, as well as any other product candidate that we may develop in the future, are subject to extensive regulation.
Failure to bring ONS-5010, or any other product candidates we may develop in the future, to market will prevent us from generating sales revenue and this will substantially harm our business. Furthermore, any delay in entering into these alliances could delay the development and commercialization of our product candidates and reduce their competitiveness even if they reach the market.
Failure to bring ONS-5010/LYTENAVA, or any other product candidates we may develop in the future, to market will prevent us from generating sales revenue and this will substantially harm our business. Furthermore, any delay in entering into these alliances could delay the development and commercialization of our product candidates and reduce their competitiveness even if they reach the market.
We will require substantial additional capital to continue to operate as a going concern. Although we continue to pursue discussions with additional potential strategic partners for ONS-5010 outside of the United States, there is no guarantee that we will be successful in reaching any such agreement, nor that such agreement, if successful, will cover the anticipated commercialization costs for ONS-5010.
We will require substantial additional capital to continue to operate as a going concern. Although we continue to pursue discussions with additional potential strategic partners for ONS-5010/LYTENAVA outside of the United States, there is no guarantee that we will be successful in reaching any such agreement, nor that such agreement, if successful, will cover the anticipated commercialization costs for ONS-5010/LYTENAVA.
We re-submitted the BLA to the FDA for ONS-5010 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 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.
Because we have limited resources and access to capital to fund our operations, we must decide which product candidates to pursue and the amount of resources to allocate to each. We are currently focusing only on one active development program, ONS-5010, and are no longer actively developing ONS-3010, ONS-1045 or the other biosimilar product candidates in our pipeline.
Because we have limited resources and access to capital to fund our operations, we must decide which product candidates to pursue and the amount of resources to allocate to each. We are currently focusing only on one active development program, ONS-5010/LYTENAVA, and are no longer actively developing ONS-3010, ONS-1045 or the other biosimilar product candidates in our pipeline.
Our operations are directly and indirectly through our current and future arrangements with healthcare professionals, principal investigators, consultants, customers and third-party payors subject to various federal and state fraud and abuse laws, including without limitation, the federal Anti-Kickback Statute, the civil False Claims Act and physician sunshine laws and regulations.
Our operations are directly and indirectly through our current and future arrangements with healthcare professionals, principal investigators, consultants, customers and third-party payors subject to various foreign, federal, and state fraud and abuse laws, including without limitation, the federal Anti-Kickback Statute, the civil False Claims Act and physician sunshine laws and regulations.
Our ability to generate revenue and achieve profitability depends on our ability, alone or with strategic collaboration partners, to successfully complete the development of, and obtain the regulatory and marketing approvals necessary to commercialize, ONS-5010 for the treatment of wet AMD, and our other targeted indications, and as appropriate, any of our other product candidates.
Our ability to generate revenue and achieve profitability depends on our ability, alone or with strategic collaboration partners, to successfully complete the development of, and obtain the regulatory and marketing approvals necessary to commercialize, ONS-5010/LYTENAVA for the treatment of wet AMD, and our other targeted indications, and as appropriate, any of our other product candidates.
Product candidates developed by our competitors may render ONS-5010 and any of our other potential product candidates uneconomical, less desirable or obsolete, and we may not be successful in marketing our product candidates against competitors. We expect additional companies to seek approval to manufacture and market anti-VEGF therapies for ophthalmic indications.
Product candidates developed by our competitors may render ONS-5010/LYTENAVA and any of our other potential product candidates uneconomical, less desirable or obsolete, and we may not be successful in marketing our product candidates against competitors. We expect additional companies to seek approval to manufacture and market anti-VEGF therapies for ophthalmic indications.
For example, we entered into a strategic partnership agreement for consulting services for ONS-5010, pursuant to which we paid a monthly fee prior to terminating such arrangement. We have also entered into service agreements for clinical trials, and co-development and license agreements for our biosimilar product candidates, and are potentially pursuing strategic partners for ONS-5010.
For example, we entered into a strategic partnership agreement for consulting services for ONS-5010/LYTENAVA, pursuant to which we paid a monthly fee prior to terminating such arrangement. We have also entered into service agreements for clinical trials, and co-development and license agreements for our biosimilar product candidates, and are potentially pursuing strategic partners for ONS-5010/LYTENAVA.
Such 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 such lawsuits is necessarily uncertain. We could be forced to expend significant resources in the defense of the pending lawsuit and any additional lawsuits, and we may not prevail.
Such 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 such lawsuits is necessarily uncertain. We could be forced to expend significant resources in the defense of the pending lawsuits and any additional lawsuits, and we may not prevail.
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 for many reasons, including: ● we may not be able to demonstrate that ONS-5010 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 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 27 Table of Contents ● 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; 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.
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, as well as additional requested CMC data indicated in the CRL to approve ONS-5010 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.
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, as well as additional requested CMC data indicated in the CRL to approve ONS-5010 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.
At subsequent Type A meetings with the FDA, we learned that the FDA requires the successful completion of an additional adequate and well-controlled trial clinical trial evaluating ONS-5010, as well as additional requested CMC data indicated in the CRL to approve ONS-5010 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 trial 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.
In addition, we expect to rely in part on preclinical, clinical and quality data generated by CROs, and other third parties for regulatory submissions for ONS-5010. While we have or will have agreements governing these third parties’ services, we have limited influence over their actual performance.
In addition, we expect to rely in part on preclinical, clinical and quality data generated by CROs, and other third parties for regulatory submissions for ONS-5010/LYTENAVA. While we have or will have agreements governing these third parties’ services, we have limited influence over their actual performance.
We continue to pursue discussions for the licensing and/or co-development rights to ONS-5010 outside of the U.S. We may not be successful in reaching agreements with such parties on terms that are as favorable to our company as we would anticipate.
We continue to pursue discussions for the licensing and/or co-development rights to ONS-5010/LYTENAVA outside of the U.S. We may not be successful in reaching agreements with such parties on terms that are as favorable to our company as we would anticipate.
We expect to experience pricing pressures in connection with the sale of ONS-5010, 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 toward managed healthcare, the increasing influence of health maintenance organizations and additional legislative changes.
We are subject, directly and indirectly, to federal and state healthcare laws and regulations, including fraud and abuse, false claims, physician payment transparency and health information privacy and security laws. If we are unable to comply or have not fully complied with such laws, we could face substantial penalties.
We are subject, directly and indirectly, to foreign, federal, and state healthcare laws and regulations, including fraud and abuse, false claims, physician payment transparency and health information privacy and security laws. If we are unable to comply or have not fully complied with such laws, we could face substantial penalties.
In such alliances, we would expect our collaboration partners to provide substantial capabilities in regulatory affairs, as well as sales and marketing. We may not be successful in entering into any such alliances, including reaching agreement with a potential partner for ONS-5010.
In such alliances, we would expect our collaboration partners to provide substantial capabilities in regulatory affairs, as well as sales and marketing. We may not be successful in entering into any such alliances, including reaching agreement with a potential partner for ONS-5010/LYTENAVA.
Some of our competitors may have ongoing clinical trials for product candidates that would treat the same indications as ONS-5010 or any future product candidates we may develop, and patients who would otherwise be eligible for our clinical trials may instead enroll in clinical trials of our competitors’ product candidates.
Some of our competitors may have ongoing clinical trials for product candidates that would treat the same indications as ONS-5010/LYTENAVA or any future product candidates we may develop, and patients who would otherwise be eligible for our clinical trials may instead enroll in clinical trials of our competitors’ product candidates.
If we are not able to retain our management and to attract, on acceptable terms, additional qualified personnel necessary for the continued development of our business, we may not be able to sustain our operations or grow our product offering beyond ONS-5010.
If we are not able to retain our management and to attract, on acceptable terms, additional qualified personnel necessary for the continued development of our business, we may not be able to sustain our operations or grow our product offering beyond ONS-5010/LYTENAVA.
If we elect or are required to delay, suspend or terminate any clinical trial, the commercial prospects of ONS-5010 or any future product candidate will be harmed and our ability to generate product revenues from this product candidate will be delayed or eliminated.
If we elect or are required to delay, suspend or terminate any clinical trial, the commercial prospects of ONS-5010/LYTENAVA or any future product candidate will be harmed and our ability to generate product revenues from this product candidate will be delayed or eliminated.
If we are unsuccessful in forming or maintaining these alliances on favorable terms, our business could be harmed. Because we are a pre-commercial biopharmaceutical company, we have found it necessary to enter into alliances with other companies.
If we are unsuccessful in forming or maintaining these alliances on favorable terms, our business could be harmed. Because we have been a pre-commercial biopharmaceutical company, we have found it necessary to enter into alliances with other companies.
We may not be successful in obtaining or maintaining necessary rights to our product candidates through acquisitions and in-licenses. We currently have rights to certain intellectual property through licenses from third parties, including Selexis, to develop ONS-5010/ONS-1045 and ONS-3010.
We may not be successful in obtaining or maintaining necessary rights to ONS-5010/LYTENAVA or our product candidates through acquisitions and in-licenses. We currently have rights to certain intellectual property through licenses from third parties, including Selexis, to develop ONS-5010/LYTENAVA/ONS-1045 and ONS-3010.
We could be forced to expend significant resources in the settlement or defense of the pending lawsuit and any potential future lawsuits, and we may not prevail in such lawsuits. Additionally, we may not be successful in having any such lawsuits dismissed or settled within the limits of our insurance coverage.
We could be forced to expend significant resources in the settlement or defense of the pending lawsuits and any potential future lawsuits, and we may not prevail in such lawsuits. Additionally, we may not be successful in having any such lawsuits dismissed or settled within the limits of our insurance coverage.
Serious adverse events observed in clinical trials could hinder or prevent market acceptance of ONS-5010 or any future product candidate. Any of these occurrences may harm our business, prospects, financial condition and results of operations significantly.
Serious adverse events observed in clinical trials could hinder or prevent market acceptance of ONS-5010/LYTENAVA or any future product candidate. Any of these occurrences may harm our business, prospects, financial condition and results of operations significantly.
If we are not successful in reducing off-label use of Avastin or other drugs with ONS-5010, our business and financial condition could be adversely affected. We currently have no marketing and sales organization.
If we are not successful in reducing off-label use of Avastin or other drugs with ONS-5010/LYTENAVA, our business and financial condition could be adversely affected. ​ We currently have no marketing and sales organization.
Despite the time and expense associated with preclinical studies and clinical trials, failure can occur at any stage. The results of preclinical and early clinical trials of ONS-5010 or any future product candidates may not be predictive of the results of our later-stage clinical trials.
Despite the time and expense associated with preclinical studies and clinical trials, failure can occur at any stage. The results of preclinical and early clinical trials of ONS-5010/LYTENAVA or any future product candidates may not be predictive of the results of our later-stage clinical trials.
For example, enrollment in the NORSE ONE and NORSE TWO studies was delayed from our original expectations. We could experience similar enrollment delays in the remaining NORSE trials (FOUR, FIVE, SIX, SEVEN and EIGHT) once they are initiated.
For example, enrollment in the NORSE ONE and NORSE TWO studies was delayed from our original expectations. We could experience similar enrollment delays in the remaining NORSE trials (FOUR, FIVE, SIX, and SEVEN) once they are initiated.
As such, we may be required to hire substantially more sales representatives and medical support liaisons to adequately support the commercialization of ONS-5010 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 costs as a result of hiring more sales representatives than necessary.
We have not established any reserve for any potential liability relating to the pending lawsuit or any potential future lawsuits. It is possible that we could, in the future, incur judgments or enter into settlements of claims for monetary damages.
We have not established any reserve for any potential liability relating to the pending lawsuits or any potential future lawsuits. It is possible that we could, in the future, incur judgments or enter into settlements of claims for monetary damages.
We are not permitted to market ONS-5010 in the United States until we receive approval from the FDA, or in any foreign country until we receive the requisite approvals from the appropriate authorities in such countries for marketing authorization.
We are not permitted to market ONS-5010/LYTENAVA in the United States until we receive approval from the FDA, or in any foreign country until we receive the requisite approvals from the appropriate authorities in such countries for marketing authorization.
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; ● 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; 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.
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. 44 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. ​ 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.
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 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 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 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.
These fluctuations may occur due to a variety of factors, many of which are out of our control and may be difficult to predict, including but not limited to: ● our ability to successfully develop, market and sell ONS-5010 and any other product candidates; ● the cost of clinical development for ONS-5010 and any other product candidates; ● the success of competitive products or technologies; ● results of clinical trials of our product candidates or those of our competitors; ● developments or disputes concerning patent applications, issued patents or other proprietary rights; ● the recruitment or departure of key personnel; ● the level of expenses related to any of our product candidates or clinical development programs; ● the results of our efforts to discover, develop, manufacture, acquire or in-license additional product candidates; 69 Table of Contents ● actual or anticipated changes in estimates as to financial results, development timelines or recommendations by securities analysts; ● variations in our financial results or those of companies that are perceived to be similar to us; ● market conditions in the pharmaceutical and biotechnology sectors; ● general economic, industry and market conditions; and ● the other factors described in this “Risk Factors” section.
These fluctuations may occur due to a variety of factors, many of which are out of our control and may be difficult to predict, including but not limited to: ● our ability to successfully develop, market and sell ONS-5010/LYTENAVA and any other product candidates; ● the cost of clinical development for ONS-5010/LYTENAVA and any other product candidates; ● the success of competitive products or technologies; ● results of clinical trials of our product candidates or those of our competitors; ● developments or disputes concerning patent applications, issued patents or other proprietary rights; ● the recruitment or departure of key personnel; ● the level of expenses related to any of our product candidates or clinical development programs; ● the results of our efforts to discover, develop, manufacture, acquire or in-license additional product candidates; ● actual or anticipated changes in estimates as to financial results, development timelines or recommendations by securities analysts; ● variations in our financial results or those of companies that are perceived to be similar to us; ● market conditions in the pharmaceutical and biotechnology sectors; ● general economic, industry and market conditions; and ● the other factors described in this “Risk Factors” section.
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 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.
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 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.
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 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.
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; 36 Table of Contents ● 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; ● 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.
We do not have in place any licensing agreements for commercialization of ONS-5010 and have only licensed ONS-5010 to our PRC-joint venture, for commercialization in greater China.
We do not have in place any licensing agreements for commercialization of ONS-5010/LYTENAVA and have only licensed ONS-5010/LYTENAVA to our PRC-joint venture, for commercialization in greater China.
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; ● 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; 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.
This lack of experience may impede our ability to obtain FDA approval in a timely manner, if at all, for ONS-5010.
This lack of experience may impede our ability to obtain FDA approval in a timely manner, if at all, for ONS-5010/LYTENAVA.
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 agencies 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; 28 Table of Contents ● imposition of a clinical hold by regulatory agencies, 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.
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.
Some of the pharmaceutical and biotechnology companies we expect to compete with include, for example, Novartis, which currently markets LUCENTIS and BEOVU, Regeneron, with its product EYLEA, Genentech, the marketer of VABYSMO, and both Biogen and Coherus with their biosimilar formulations of LUCENTIS, all of which have been approved for use in patients with wet AMD.
Some of the pharmaceutical and biotechnology companies we expect to compete with include, for example, Novartis, which currently markets LUCENTIS and BEOVU, Regeneron, with its product EYLEA, Genentech, the marketer of VABYSMO, both Biogen and Coherus with their biosimilar formulations of LUCENTIS and Amgen with their biosimilar formulation of EYLEA, all of which have been approved for use in patients with wet AMD.
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. 37 Table of Contents Adverse side effects or other safety risks associated with ONS-5010 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. ​ 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.
In addition, the combinations will likely not have been previously tested and may, among other 64 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.
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.
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.
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.
Further, others, including regulatory agencies may not accept or agree with our assumptions, estimates, calculations, conclusions or analyses or may interpret or weigh the importance of data differently, which could impact the value of the particular development program, the approvability or commercialization of the particular product candidate or product and our company in general.
Further, others, including regulatory authorities may not accept or agree with our assumptions, estimates, calculations, conclusions or analyses or may interpret or weigh the importance of data differently, which could impact the value of the particular development program, the approvability or commercialization of the particular product candidate or product and our company in general.
In addition, any of these regulatory authorities may change the requirements for the approval of a product candidate even after reviewing and providing comments or advice on a protocol for a Phase 3 clinical trial that has the potential to result in FDA or other agencies’ approval.
In addition, any of these regulatory authorities may change the requirements for the approval of a product candidate even after reviewing and providing comments or advice on a protocol for a Phase 3 clinical trial that has the potential to result in FDA or other authorities’ approval.
In addition, changes in regulatory requirements and policies may occur, and we may need to amend clinical trial protocols to comply with these changes. Amendments may require us to resubmit our clinical trial protocols to IRBs for reexamination, which may impact the costs, timing or successful completion of a clinical trial.
In addition, changes in regulatory requirements and policies may occur, and we may need to amend clinical trial protocols to comply with these changes. Amendments may require us to resubmit our clinical trial protocols to IRBs or Ethics Committees for reexamination, which may impact the costs, timing or successful completion of a clinical trial.
Any disclosure, either intentional or unintentional, by our employees, the employees of third parties with whom we share our facilities or third-party consultants and vendors that we engage to perform research, clinical trials or manufacturing activities, or misappropriation by third parties (such as through a cybersecurity breach) of our trade secrets or proprietary information could enable competitors to duplicate or surpass our 47 Table of Contents technological achievements, thus eroding our competitive position in our market.
Any disclosure, either intentional or unintentional, by our employees, the employees of third parties with whom we share our facilities or third-party consultants and vendors that we engage to perform research, clinical trials or manufacturing activities, or misappropriation by third parties (such as through a cybersecurity breach) of our trade secrets or proprietary information could enable competitors to duplicate or surpass our technological achievements, thus eroding our competitive position in our market.
Our amended and restated certificate of incorporation and our amended and restated bylaws, each as amended, provide that the Court of Chancery of the State of Delaware is the exclusive forum for the following types of actions or proceedings under Delaware statutory or common law: any derivative action or proceeding brought on our behalf; any action asserting a breach of fiduciary duty; any action asserting a claim against us arising pursuant to the Delaware General Corporation 73 Table of Contents Law, our amended and restated certificate of incorporation or our amended and restated bylaws, each as amended, or any action asserting a claim against us that is governed by the internal affairs doctrine.
Our amended and restated certificate of incorporation and our amended and restated bylaws, each as amended, provide that the Court of Chancery of the State of Delaware is the exclusive forum for the following types of actions or proceedings under Delaware statutory or common law: any derivative action or proceeding brought on our behalf; any action asserting a breach of fiduciary duty; any action asserting a claim against us arising pursuant to the Delaware General Corporation Law, our amended and restated certificate of incorporation or our amended and restated bylaws, each as amended, or any action asserting a claim against us that is governed by the internal affairs doctrine.
Misconduct by these parties could include intentional, reckless and/or negligent conduct that violates FDA regulations, including those laws requiring the reporting of true, complete and accurate information to the FDA, manufacturing standards, federal and state healthcare laws and regulations, and laws that require the true, complete and accurate reporting of financial information or data.
Misconduct by these parties could include intentional, reckless and/or negligent conduct that violates FDA regulations, including those laws requiring the reporting of true, complete and accurate information to the FDA, manufacturing standards, federal and state healthcare laws and regulations, and laws that require the true, complete and accurate reporting of financial information or data, and comparable foreign regulations.
If our board of directors does not elect to reduce the annual increases in the number of shares available for future grant under the 2015 Plan or the ESPP, our stockholders may experience additional dilution, which could cause the market price of our securities to fall.
If our board of directors does not elect to reduce the annual increases in the number of shares available for future grant under the 2024 Plan or the ESPP, our stockholders may experience additional dilution, which could cause the market price of our securities to fall.
Moreover, increasing efforts by governmental and third-party payors in the United States and abroad to control healthcare costs may cause such organizations to limit both coverage and the level of reimbursement for new products approved and, as a result, they may not cover or provide adequate payment for ONS-5010, or any other product candidates we may develop in the future.
Moreover, increasing efforts by governmental and third-party payors in the United States and abroad to control healthcare costs may cause such organizations to limit both coverage and the level of reimbursement for new products approved and, as a result, they may not cover or provide adequate payment for ONS-5010/LYTENAVA, or any other product candidates we may develop in the future that may be approved.
Foreign Corrupt Practices Act, its books and records provisions or its anti-bribery provisions. If we fail to comply with environmental, health and safety laws and regulations, we could become subject to fines or penalties or incur costs that could harm our business.
Foreign Corrupt Practices Act, its books and records provisions or its anti-bribery provisions, or comparable foreign requirements. If we fail to comply with environmental, health and safety laws and regulations, we could become subject to fines or penalties or incur costs that could harm our business.
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.
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.
The degree of market acceptance of 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; 40 Table of Contents ● 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, or any other product candidates we may pursue, if approved; ● our ability to maintain compliance with regulatory requirements; and ● labeling or naming imposed by FDA or other regulatory agencies.
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.
As in the case of our formulation patent filings, it is highly uncertain and we cannot predict whether our patent filings on process enhancements will afford us a competitive advantage against third parties. 53 Table of Contents Obtaining and maintaining our patent protection depends on compliance with various procedural requirements, document submissions, fee payment and other requirements imposed by governmental patent agencies.
As in the case of our formulation patent filings, it is highly uncertain and we cannot predict whether our patent filings on process enhancements will afford us a competitive advantage against third parties. Obtaining and maintaining our patent protection depends on compliance with various procedural requirements, document submissions, fee payment and other requirements imposed by governmental patent agencies.
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.
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.
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.
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.
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 63 Table of Contents 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 stringent.
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.
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.
If ONS-5010 or any other product candidates we may develop in the future are approved but fail to achieve an adequate level of acceptance by physicians, patients, third-party payors and others in the medical community, we will not be able to generate sufficient revenue to become or remain profitable.
If ONS-5010/LYTENAVA or any other product candidates we may develop in the future that are approved fail to achieve an adequate level of acceptance by physicians, patients, third-party payors and others in the medical community, we will not be able to generate sufficient revenue to become or remain profitable.
If we are unable to obtain and maintain effective patent rights for our product candidates or any future product candidates, we may not be able to prevent competitors from using technologies we consider important in the development and commercialization of our product candidates, resulting in loss of any potential competitive advantage our patents may have otherwise afforded us.
If we are unable to obtain and maintain effective patent rights for ONS-5010/LYTENAVA or any future product candidates, we may not be able to prevent competitors from using technologies we consider important in the development and commercialization of ONS-5010/LYTENAVA or any future product candidates, resulting in loss of any potential competitive advantage our patents may have otherwise afforded us.

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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. The pending lawsuit 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 lawsuit and any other related lawsuits is necessarily uncertain.
Biggest changeThe 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 complaint alleges, among other things, that we violated Sections 10(b) and 20(a) of the Exchange Act and SEC Rule 10b-5 by failing to disclose that there was an alleged lack of evidence supporting ONS-5010 as a treatment for wet AMD and that we and/or our manufacturing partner had deficient CMC controls for ONS-5010, which remained unresolved at the time our BLA was re-submitted to the FDA and, as a result, the FDA was unlikely to approve our BLA, and that our stock price dropped when such information was disclosed.
The complaint alleges, among other things, that we violated Sections 10(b) and 20(a) of the Exchange Act and SEC Rule 10b-5 by failing to disclose that there was an alleged lack of evidence supporting ONS-5010/LYTENAVA as a treatment for wet AMD and that we and/or our manufacturing partner had deficient CMC controls for ONS-5010/LYTENAVA, which remained unresolved at the time our BLA was re-submitted to the FDA and, as a result, the FDA was unlikely to approve our BLA, and that our stock price dropped when such information was disclosed.
We could be forced to expend significant resources in the defense of the pending lawsuit and any additional lawsuits, and we may not prevail. In addition, we may incur substantial legal fees and costs in connection with such lawsuits.
We could be forced to expend significant resources in the defense of the pending lawsuits and any additional lawsuits, and we may not prevail. In addition, we may incur substantial legal fees and costs in connection with such lawsuits.
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. ​ 75 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. ​ 85 Table of Contents PART II
We currently are not able to estimate the possible cost to us from these matters, as the pending lawsuit is currently at an early stage, and we cannot be certain how long it may take to resolve the pending lawsuit or the possible amount of any damages that we may be required to pay.
We currently are not able to estimate the possible cost to us from these matters, as the pending lawsuits are currently at an early stage, and we cannot be certain how long it may take to resolve the pending lawsuits or the possible amount of any damages that we may be required to pay.
Such amounts could be material to our financial statements if we do not prevail in the defense of the pending lawsuit 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 lawsuit and any other related 74 Table of Contents 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 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.
The class action complaint alleges violations of 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 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.
Added
The 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.
Added
The derivative complaint alleges that defendants breached their fiduciary duties by causing and/or allowing the company to violate federal securities laws based on the same alleged misstatements as the securities class action. The derivative complaint also alleges defendants violated Section 14(a) of the Exchange Act, as well as claims for contribution, unjust enrichment, and waste of corporate assets.

Item 5. Market for Registrant's Common Equity

Market for Common Equity — stock, dividends, buybacks

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Biggest changeIssuer Purchases of Equity Securities We did not repurchase any of our equity securities during fiscal year ended September 30, 2023. ​ 76 Table of Contents
Biggest changeIssuer 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
Item 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, 2023, there were approximately 80 stockholders of record of our common stock.
Item 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.

Item 7. Management's Discussion & Analysis

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

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Biggest changeThere is also a risk that due to regulatory changes, such as suspensions on the use of NOLs, or other unforeseen reasons, our existing NOLs could expire or otherwise be unavailable to offset future income tax liabilities. 82 Table of Contents Results of Operations Comparison of Years Ended September 30, 2023 and 2022 ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year ended September 30, ​ ​ ​ ​ 2023 2022 Change Operating expenses: ​ ​ ​ ​ ​ ​ ​ ​ ​ Research and development ​ $ 26,452,942 ​ $ 42,330,856 ​ $ (15,877,914) General and administrative ​ ​ 26,673,440 ​ ​ 20,739,897 ​ ​ 5,933,543 Loss from operations ​ ​ (53,126,382) ​ ​ (63,070,753) ​ ​ 9,944,371 ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Loss on equity method investment ​ ​ 10,998 ​ ​ 48,730 ​ ​ (37,732) Interest expense, net ​ ​ 1,559,748 ​ ​ 1,487,456 ​ ​ 72,292 Loss on extinguishment of debt ​ ​ 577,659 ​ ​ 1,025,402 ​ ​ (447,743) Change in fair value of promissory notes ​ ​ 3,756,000 ​ ​ 882,903 ​ ​ 2,873,097 Change in fair value of warrant liability ​ ​ (50,919) ​ ​ (465,780) ​ ​ 414,861 Loss before income taxes ​ ​ (58,979,868) ​ ​ (66,049,464) ​ ​ 7,069,596 Income tax expense ​ ​ 2,800 ​ ​ 2,800 ​ ​ — Net loss ​ $ (58,982,668) ​ $ (66,052,264) ​ $ 7,069,596 ​ Research and Development Expenses The following table summarizes our research and development expenses by functional area for the years ended September 30, 2023 and 2022: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year ended September 30, ​ 2023 2022 ONS-5010 development ​ $ 28,718,140 ​ $ 29,596,954 Compensation and related benefits ​ ​ 2,126,772 ​ ​ 2,392,139 Stock-based compensation ​ ​ 986,598 ​ ​ 2,691,330 Other research and development ​ ​ (5,378,568) ​ ​ 7,650,433 Total research and development expenses ​ $ 26,452,942 ​ $ 42,330,856 ​ Research and development expenses for the year ended September 30, 2023 decreased by $15.9 million compared to the year ended September 30, 2022.
Biggest changeResults of Operations Comparison of Years Ended September 30, 2024 and 2023 ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year ended September 30, ​ ​ ​ ​ 2024 2023 Change Operating expenses: ​ ​ ​ ​ ​ ​ ​ ​ ​ Research and development ​ $ 41,763,047 ​ $ 26,452,942 ​ $ 15,310,105 General and administrative ​ ​ 29,940,188 ​ ​ 26,673,440 ​ ​ 3,266,748 Loss from operations ​ ​ (71,703,235) ​ ​ (53,126,382) ​ ​ (18,576,853) ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Loss on equity method investment ​ ​ 100,742 ​ ​ 10,998 ​ ​ 89,744 Interest income ​ ​ (906,150) ​ ​ (971,480) ​ ​ 65,330 Interest expense ​ ​ 3,156,964 ​ ​ 2,531,228 ​ ​ 625,736 Loss on extinguishment of debt ​ ​ — ​ ​ 577,659 ​ ​ (577,659) Change in fair value of promissory notes ​ ​ 2,457,153 ​ ​ 3,756,000 ​ ​ (1,298,847) Warrant related expenses ​ ​ 37,490,012 ​ ​ — ​ ​ 37,490,012 Change in fair value of warrant liability ​ ​ (38,638,042) ​ ​ (50,919) ​ ​ (38,587,123) Loss before income taxes ​ ​ (75,363,914) ​ ​ (58,979,868) ​ ​ (16,384,046) Income tax expense ​ ​ 2,800 ​ ​ 2,800 ​ ​ — Net loss ​ $ (75,366,714) ​ $ (58,982,668) ​ $ (16,384,046) ​ Research and Development Expenses The following table summarizes our research and development expenses by functional area for the years ended September 30, 2024 and 2023: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year ended September 30, ​ 2024 2023 ONS-5010/LYTENAVA development ​ $ 37,355,884 ​ $ 28,718,140 Compensation and related benefits ​ ​ 2,507,635 ​ ​ 2,126,772 Stock-based compensation ​ ​ 800,956 ​ ​ 986,598 Other research and development ​ ​ 1,098,572 ​ ​ (5,378,568) Total research and development expenses ​ $ 41,763,047 ​ $ 26,452,942 ​ Research and development expenses for the year ended September 30, 2024 increased by $15.3 million compared to the year ended September 30, 2023.
Further, due to current market volatility, we may be unable to raise additional funds or enter into such other arrangements when needed on favorable terms or at all. There are no assurances that we will be successful in obtaining an adequate level of financing for the commercialization of ONS-5010 or the development of any other current or future product candidates.
Further, due to current market volatility, we may be unable to raise additional funds or enter into such other arrangements when needed on favorable terms or at all. There are no assurances that we will be successful in obtaining an adequate level of financing for the commercialization of ONS-5010/LYTENAVA or the development of any other current or future product candidates.
Alternatively, we will be required to, among other things, modify our clinical trial plans for ONS-5010 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 U.S. Bankruptcy Code.
There are no assurances that we will be successful in obtaining an adequate level of financing for the development and commercialization of ONS-5010 or any other current or future product candidates. If we are unable to secure adequate additional funding, our business, operating results, financial condition and cash flows may be materially and adversely affected.
There are no assurances that we will be successful in obtaining an adequate level of financing for the development and commercialization of ONS-5010/LYTENAVA or any other current or future product candidates. If we are unable to secure adequate additional funding, our business, operating results, financial condition and cash flows may be materially and adversely affected.
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.
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.
We re-submitted the BLA to the FDA for ONS-5010 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.
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.
We will need substantial additional financing to fund our operations and to commercially launch ONS-5010 or any other product candidate we may develop. Management is currently evaluating various strategic opportunities to obtain the required funding for future operations.
We will need substantial additional financing to fund our operations and to commercially launch ONS-5010/LYTENAVA or any other product candidate we may develop. Management is currently evaluating various strategic opportunities to obtain the required funding for future operations.
We anticipate incurring additional losses until such time, if ever, that we can generate significant sales of ONS-5010 or any other product candidate we may develop. We will need substantial additional financing to fund our operations and to commercially develop ONS-5010 or any other product candidate we may develop.
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 will need substantial additional financing to fund our operations and to commercially develop ONS-5010/LYTENAVA or any other product candidate we may develop.
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 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.
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 $2.50 per share (subject to adjustments for stock splits and stock combinations) for a period of 30 consecutive trading days.
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.
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.
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.
Upon the occurrence of certain events described in the December 2022 Note, including, among others, the Company’s failure to pay amounts due and payable under the December 2022 Note, events of insolvency or bankruptcy, failure to observe covenants contained in the Securities Purchase Agreement and the December 2022 Note, breaches of representations and warranties in the Securities Purchase Agreement, and the occurrence of certain transactions without the Lender’s consent (each such event, a Trigger Event), the Lender shall have the right, subject to certain exceptions, to increase the balance of the December 2022 Note by 10% for a Major Trigger Event (as defined in the December 2022 Note) and 5% for a Minor Trigger Event (as defined in the December 2022 Note).
Upon the occurrence of certain events described in the December 2022 Note, including, among others, the Company’s failure to pay amounts due and payable under the December 2022 Note, events of insolvency or bankruptcy, failure to observe covenants contained in the Securities Purchase Agreement and the December 2022 Note, breaches of representations and warranties in the Securities Purchase Agreement, and the occurrence of certain transactions without the Lender’s consent (each such event, a “Trigger Event”), the Lender shall have the right, subject to certain exceptions, to increase the balance of the December 2022 Note by 10% for a Major Trigger Event (as defined in the December 2022 Note) and 5% for a Minor Trigger Event (as defined in the December 2022 Note).
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 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; 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.
This uncertainty is due 80 Table of Contents to the numerous risks and uncertainties associated with the duration and cost of clinical trials, which vary significantly over the life of a project as a result of many factors, including: ● the number of clinical sites included in the trials; ● the length of time required to enroll suitable patients; ● the number of patients that ultimately participate in the trials; ● the number of doses patients receive; ● the duration of patient follow-up; ● the results of our clinical trials; ● the establishment of commercial manufacturing capabilities; ● the receipt of marketing approvals; and ● the commercialization of product candidates. ​ Our expenditures are subject to additional uncertainties, including the terms and timing of regulatory approvals.
This uncertainty is due to the numerous risks and uncertainties associated with the duration and cost of clinical trials, which vary significantly over the life of a project as a result of many factors, including: ● the number of clinical sites included in the trials; ● the length of time required to enroll suitable patients; ● the number of patients that ultimately participate in the trials; ● the number of doses patients receive; ● the duration of patient follow-up; ● the results of our clinical trials; ● the establishment of commercial manufacturing capabilities; ● the receipt of marketing approvals; and ● the commercialization of product candidates. ​ Our expenditures are subject to additional uncertainties, including the terms and timing of regulatory approvals.
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, as well as additional requested CMC data indicated in the CRL to approve ONS-5010 for use in wet AMD.
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.
On May 16, 2023, we entered into an At-the-Market Sales Agreement with BTIG, LLC (“BTIG”), as sales agent (the “BTIG ATM Agreement” or the “BTIG ATM Offering”), under which we may issue and sell shares of our common stock having an aggregate offering price of up to $100,000,000 from time to time through BTIG.
On May 16, 2023, we entered into an At-the-Market Sales Agreement with BTIG, LLC (“BTIG”), as sales agent (the “BTIG ATM Agreement” or the “BTIG 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.
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 for timing of payments associated with ONS-5010 development costs, partially offset by an increase in other assets of $0.2 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.
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 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 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.
If a Trigger Event is not cured within ten (10) trading days of written notice thereof from the Lender, it will result in an event of default (such event, an Event of Default).
If a Trigger Event is not cured within ten (10) trading days of written notice thereof from the Lender, it will result in an event of default (such event, an “Event of Default”).
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, loss on extinguishment of debt, loss on equity method investment and depreciation and amortization expense.
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.
We plan to finance our future operations with a combination of proceeds from 88 Table of Contents potential strategic collaborations, sale of the development and commercial rights to our drug product candidates, the issuance of equity securities, the issuance of additional debt, and revenues from potential future product sales, if any.
We plan to finance our future operations with a combination of proceeds from potential strategic collaborations, sale of the development and commercial rights to our drug product candidates, the issuance of equity securities, the issuance of additional debt, 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.
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.
On November 16, 2021, we received $10.0 million in net proceeds from the issuance of the November 2021 Note, with a face amount of $10.2 million. The November 2021 Note bore interest at a rate of 9.5% per annum, was due to mature January 1, 2023 and included an original issue discount of $0.2 million.
On November 16, 2021, we received $10.0 million in net proceeds from the issuance of an unsecured promissory note (the “November 2021 Note”), with a face amount of $10.2 million. The November 2021 Note bore interest at a rate of 9.5% per annum, was due to mature January 1, 2023 and included an original issue discount of $0.2 million.
The study design for our clinical program to evaluate ONS-5010 as an ophthalmic formulation of bevacizumab was reviewed at an end of Phase 2 meeting with the FDA in April 2018, and we filed our 77 Table of Contents investigational new drug application, or IND, with the FDA in the first quarter of calendar 2019.
The study design for our clinical program to evaluate ONS-5010/LYTENAVA as an ophthalmic formulation of bevacizumab was reviewed at an end of Phase 2 meeting with the FDA in April 2018, and we filed our investigational new drug application, or IND, with the FDA in the first quarter of calendar 2019.
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.
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 could prepay all or a portion of the note at any time by paying 105% of the outstanding balance elected for pre-payment. On December 28, 2022, we prepaid the November 2021 Note in full by paying 105% of the outstanding balance.
We could prepay all or a portion of the note at any time by paying 105% of the outstanding balance elected for prepayment. On December 28, 2022, we prepaid the November 2021 Note in full by paying 105% of the outstanding balance.
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 CMC issues, open observations from pre-approval manufacturing inspections, and a lack of substantial evidence.
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.
Any payments made by us in cash, including prepayments or repayment at maturity, will be subject to an additional fee of 7.5%.
Any payments made by the Company in cash, including prepayments or repayment at maturity, will be subject to an additional fee of 7.5%.
Under the December 2022 Note, “Conversion Price” means, prior to a Major Trigger Event, $2.00 per share (subject to adjustment for stock splits and stock combinations), and following a Major Trigger Event, the lesser of (i) $2.00 per share (subject to adjustment for stock splits and stock combinations), and (ii) 90% multiplied by the lowest closing bid price of the Company’s common stock in the three trading days prior to the date on which the conversion notice is delivered.
Prior to April 1, 2024, under the December 2022 Note, “Conversion Price” meant, prior to a Major Trigger Event, $40.00 per share (subject to adjustment for stock splits and stock combinations), and following a Major Trigger Event, the lesser of (i) $40.00 per share (subject to adjustment for stock splits and stock combinations), and (ii) 90% multiplied by the lowest closing bid price of the Company’s common stock in the three trading days prior to the date on which the conversion notice is delivered.
We may make payments (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.
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 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, 2023 was $59.0 million. We also had a net loss of $66.1 million for the year ended September 30, 2022. 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. 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 incurred financing costs of $353,688, which were capitalized and are being reclassified to additional paid in capital on a pro rata basis when we sell common stock under the BTIG ATM Offering.
We incurred financing costs of $0.4 million, which were capitalized and are being reclassified to additional paid in capital on a pro rata basis when we sell common stock under the BTIG ATM Offering.
As of September 30, 2023, we also had federal and state R&D tax credit carryforwards of $11.2 million and $0.8 million, respectively, that will begin to expire in 2032 and 2033, respectively.
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.
If the Conversion Price is below $0.1756 per share, the Company will be required to satisfy a conversion notice from the Lender in cash.
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.
In August 2020, we reported achieving the anticipated safety and efficacy and positive proof-of-concept topline results from NORSE ONE, a clinical experience study. NORSE TWO is our pivotal Phase 3 clinical trial comparing ONS-5010 (bevacizumab-vikg) to ranibizumab (LUCENTIS).
In August 2020, we reported achieving the anticipated safety and efficacy proof-of-concept results from NORSE ONE, a clinical experience study. NORSE TWO was our pivotal Phase 3 clinical trial comparing ONS-5010/LYTENAVA to ranibizumab (LUCENTIS).
This use of cash was partially offset by $11.1 million of non-cash items such as stock-based compensation, non-cash interest expense, change in fair value of warrant liability, change in fair value of promissory notes, loss on extinguishment of debt, loss on equity method investment and depreciation and amortization expense.
This use of cash was partially offset by $9.6 million of non-cash items such as stock-based compensation, non-cash interest expense, change in fair value of promissory notes, warrant related expense, change in fair value of warrant liability, loss on equity method investment and depreciation and amortization expense.
Financing Activities During the year ended September 30, 2023, net cash provided by financing activities was $49.0 million, primarily attributable to $23.2 million in net proceeds from a registered direct equity offering in December 2022 of an aggregate of 28,460,831 shares of our common stock, $7.2 million in net proceeds from the sale of common stock under our Wainwright ATM Offering and BTIG ATM Offering and $30.0 million in net proceeds from the issuance of the December 2022 Note with a face amount of $31.8 million in December 2022.
During the year ended September 30, 2023, net cash provided by financing activities was $49.0 million, primarily attributable to $23.2 million in net proceeds from a registered direct equity offering in December 2022 of an aggregate of 1,423,041 shares of our common stock, $7.2 million in net proceeds from the sale of common stock under our prior at-the-market offering program and BTIG ATM Offering and $30.0 million in net proceeds from the issuance of the December 2022 Note with a face amount of $31.8 million in December 2022.
In December 2022, in a registered direct equity offering to certain institutional and accredited investors, including GMS Ventures, our largest stockholder, we issued 28,460,831 shares of common stock at a purchase price per share of $0.8784 for $23.2 million in net proceeds after payment of placement agent fees and other offering costs.
In December 2022, in a registered direct equity offering to certain institutional and accredited investors, including GMS Ventures, our largest stockholder, we issued 1,423,041 shares of common stock at a purchase price per share of $17.568 for $23.2 million in net proceeds after payment of placement agent fees and other offering costs.
GMS Ventures purchased an aggregate of 14,230,418 shares of common stock in the registered direct equity offering. In connection with the registered direct equity offering, we issued to M.S.
GMS Ventures purchased an aggregate of 711,520 shares of common stock in the registered direct equity offering. In connection with the registered direct equity offering, we issued to M.S.
Howells & Co., as placement agent for certain accredited investors in 85 Table of Contents the offering, warrants to purchase up to an aggregate of 515,755 shares of common stock, which will be exercisable commencing on the one-year anniversary of the closing of the offering at an exercise price of $1.05 per share, which warrants have a three-year term.
Howells & Co., as placement agent for certain accredited investors in the offering, 95 Table of Contents warrants to purchase up to an aggregate of 25,787 shares of common stock, which will be exercisable commencing on the one-year anniversary of the closing of the offering at an exercise price of $21.00 per share, which warrants have a three-year term.
Our initial BLA submission for ONS-5010 in wet AMD involved three clinical trials, which we refer to as NORSE ONE, NORSE TWO and NORSE THREE.
Our BLA and MAA submissions for ONS-5010/LYTENAVA in wet AMD involved three clinical trials, which we refer to as NORSE ONE, NORSE TWO and NORSE THREE.
As of September 30, 2023, we had federal and state NOL carryforwards of $371.7 million and $207.5 million, respectively, that will begin to expire in 2030 and 2039, respectively. As of September 30, 2023, we had federal foreign tax credit carryforwards of $1.6 million available to reduce future tax liabilities, which begin to expire starting in 2023.
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.
During the year ended September 30, 2023, we sold 3,578,223 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.
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.
We will need to raise substantial additional capital to fund our planned future operations, receive approval for and commercialize ONS-5010, commence and continue clinical trials, or develop other product candidates.
These factors raise substantial doubt about our ability to continue as a going concern. We will need to raise substantial additional capital to fund our planned future operations, receive approval for and commercialize ONS-5010/LYTENAVA, commence and continue clinical trials, or develop other product candidates.
The topline results reported from NORSE TWO in August 2021 showed that ONS-5010 met the primary and key secondary endpoint for efficacy with clinically impactful change observed for treated patients.
The topline results reported from NORSE TWO in August 2021 showed that ONS-5010/LYTENAVA met the primary and key secondary endpoints for efficacy with clinically impactful change observed for treated patients. In March 2021, we reported that the results from NORSE THREE showed a positive safety profile for ONS-5010/LYTENAVA.
While our significant accounting policies are described in more detail in the notes to our audited consolidated financial statements appearing elsewhere in this Annual Report on Form 10-K we believe that the following accounting policies are those most critical to the judgments and estimates used in the preparation of our consolidated financial statements. 89 Table of Contents Research and Development Expenses As part of the process of preparing our consolidated financial statements, we are required to estimate our prepaid and accrued research and development expenses.
While our significant accounting policies are described in more detail in the notes to our audited consolidated financial statements appearing elsewhere in this Annual Report on Form 10-K we believe that the following accounting policies are those most critical to the judgments and estimates used in the preparation of our consolidated financial statements.
The Lender has the right to convert the December 2022 Note at the Conversion Price (as defined below). The principal amount and Conversion Price of the December 2022 Note are subject to adjustment upon 87 Table of Contents certain triggering events.
Since April 1, 2023, the Lender has the right to convert the December 2022 Note at the Conversion Price (as defined below). The principal amount and Conversion Price of the December 2022 Note were subject to adjustment upon certain triggering events.
In December 2023, we submitted a Special Protocol Assessment, or SPA, to the FDA for this study (NORSE EIGHT) seeking confirmation that it will meet the requirements for a second adequate and well-controlled clinical trial to support our planned resubmission of the ONS-5010 BLA. A response from the FDA is expected in early February 2024.
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 March 2022, we submitted a Biologics License Application, or BLA, with the FDA for ONS-5010 (LYTENAVA (bevacizumab-vikg)), an investigational ophthalmic formulation of bevacizumab, which we have developed to be administered as an intravitreal injection for the treatment of wet AMD and other retinal diseases.
Separately, in March 2022, we submitted a BLA with the FDA for ONS-5010/LYTENAVA, an investigational ophthalmic formulation of bevacizumab, which we have developed to be administered as an intravitreal injection for the treatment of wet AMD and other retinal diseases. In May 2022, we voluntarily withdrew our BLA to provide additional information requested by the FDA.
Our consolidated financial statements do not include any adjustments related to the recoverability and classification of recorded asset amounts or the amounts and classification of liabilities that might result from the outcome of this uncertainty.
These factors raise substantial doubt about our ability to continue as a going concern. Our consolidated financial statements do not include any adjustments related to the recoverability and classification of recorded asset amounts or the amounts and classification of liabilities that might result from the outcome of this uncertainty.
We anticipate we will incur net losses and negative cash flow from operations for the foreseeable future. We may not be able to initiate commercialization of ONS-5010 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.
During the year ended September 30, 2022, we used $56.7 million of cash in operating activities resulting primarily from our net loss of $66.1 million.
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.
We anticipate that our general and administrative expenses will increase if and when we believe a regulatory approval of a product candidate appears likely, and we anticipate an increase in payroll and expense as a result of our preparation for commercial operations, particularly as it relates to the sales and marketing of our product.
We anticipate that our general and administrative expenses will increase if and when we believe a regulatory approval of a product candidate appears likely, and we anticipate an increase in payroll and expense as a result of our preparation for commercial operations, particularly as it relates to the sales and marketing of our product. 91 Table of Contents Loss on equity method investment Loss on equity method investment represents our proportionate share for the period of the net loss of our investee to which the equity method of accounting is applied.
Components of Our Results of Operations Research and Development Expenses Research and development expense consists of expenses incurred in connection with the discovery and development of our product candidates. We expense research and development costs as incurred.
The disclosure of our results of operations reflect the reverse stock split for all periods presented. Research and Development Expenses Research and development expense consists of expenses incurred in connection with the discovery and development of our product candidates. We expense research and development costs as incurred.
Overview We are a biopharmaceutical company working to launch the first ophthalmic formulation of bevacizumab approved by the U.S. Food and Drug Administration, or FDA, for use in retinal indications.
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.
The net cash outflow of $1.7 million from changes in our operating assets and liabilities was primarily due to an increase in prepaid expenses of $3.1 million for prepayments associated with ONS-5010 development costs, partially offset by an increase in accounts payable and accrued expenses of $1.5 million.
The net cash outflow of $3.0 million from changes in our operating assets and liabilities was primarily due to an increase in prepaid expenses of $4.9 million for timing of payments associated with ONS-5010/LYTENAVA development costs relating to clinical trial and drug development costs partially offset by an increase in accounts payable and accrued expenses of $1.9 million due to professional fees associated with our EU launch activities.
We have also licensed rights to our legacy biosimilar product candidates (ONS-3010, ONS-1045 and ONS-1050) in other markets. 79 Table of Contents Syntone – Private Placement and PRC Joint Venture In May 2020, we entered into a stock purchase agreement with Syntone, pursuant to which we sold and issued in a private placement in June 2020, 16,000,000 shares of our common stock at a purchase price of $1.00 per share, for aggregate gross proceeds of $16.0 million.
Syntone – Private Placement and PRC Joint Venture In May 2020, we entered into a stock purchase agreement with Syntone, pursuant to which we sold and issued in a private placement in June 2020, 800,000 shares of our common stock at a purchase price of $20.00 per share, for aggregate gross proceeds of $16.0 million.
We do not believe our current cash resources of $23.4 million as of September 30, 2023 are sufficient to fund our operations through one year from the Form 10-K filing date as a result of the costs associated with initiating the planned NORSE EIGHT clinical trial and the April 1, 2024 maturity date of the December 2022 Note, as amended in December 2023.
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.
NORSE EIGHT will be 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 or 0.5 mg ranibizumab intravitreal injections. Subjects will receive injections at Day 0 (randomization), Week 4, and Week 8 visits. Approximately 400 patients are expected to be enrolled in the study.
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.
This income was attributed to a decline in the price of our common stock during those periods. In fiscal year 2023, we recorded income of $0.1 million, compared to $0.5 million in fiscal year 2022. Liquidity and Capital Resources We have not generated any revenue from product sales.
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.
Our goal is to launch directly in the United States as the first and only approved ophthalmic bevacizumab for the treatment of wet age-related macular degeneration, or wet AMD, diabetic macular edema, or DME, and branch retinal vein occlusion, or BRVO.
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.
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. The December 2022 Note bears interest at 9.5% per annum and matures on January 1, 2024.
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.
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. Income Taxes During the years ended September 30, 2023 and 2022, we had no accruals for foreign withholding taxes in connection with our collaboration and licensing agreements.
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.
If approved, we believe ONS-5010 has potential to mitigate risks associated with off-label use of unapproved bevacizumab. In the United States, approximately 66.3% of new patient starts are off-label repackaged bevacizumab (ASRS 2022 Membership Survey Presented at ASRS NY 2022).
If approved in the United States, we believe ONS-5010/LYTENAVA has potential to mitigate risks associated with off-label use of unapproved bevacizumab.
We are currently assessing the costs to conduct the additional study and will need to secure additional funding to complete the study. 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 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.
No other terms of the December 2022 Note were amended. Funding Requirements We plan to focus in the near term on supporting the review of our BLA submission for ONS-5010 with the FDA and to prepare for the potential launch of LYTENAVA TM , if approved, to support the generation of commercial revenues.
Funding Requirements We plan to focus in the near term on supporting the review of our BLA submission for ONS-5010/LYTENAVA with the FDA and to prepare for the potential launch of ONS-5010/LYTENAVA to support the generation of commercial revenues. We anticipate we will incur net losses and negative cash flow from operations for the foreseeable future.
We anticipate incurring additional losses until such time, if ever, that we can generate significant sales of ONS-5010 or any other product candidate we may develop. 78 Table of Contents On March 26, 2021, we entered into an At-the-Market Offering Agreement with H.C.
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.
The agreements reached with the FDA on these SPAs cover the protocols for NORSE FOUR, a registration clinical trial evaluating ONS-5010 to treat BRVO, and NORSE FIVE and NORSE SIX, two registration clinical trials evaluating ONS-5010 to treat exudative age related macular degeneration, or DME.
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.
During the year ended September 30, 2023, we sold 895,391 shares of common stock under our Wainwright ATM Offering for $1.1 million in net proceeds, and the fees paid to the sales agent were immaterial.
The total payment was $11.9 million, which included interest of $1.2 million and a prepayment fee of $0.6 million. During the year ended September 30, 2023, we sold 44,769 shares of common stock under our prior at-the-market offering program for $1.1 million in net proceeds, and the fees paid to the sales agent were immaterial.
The December 2022 Note contains customary covenants, including a restriction on our ability to pledge certain of our assets, subject to certain exceptions, without the Lender’s consent. The Lender has have the right to convert the December 2022 Note at an initial conversion price of $2.00 per share.
The December 2022 Note contains customary covenants, including a restriction on our ability to pledge certain ofour assets, subject to certain exceptions, without the Lender’s consent. The principal amount and conversion price of the December 2022 Note are subject to adjustment upon certain triggering events.
The principal amount and conversion price of the December 2022 Note are subject to adjustment upon certain triggering events. See “Description of Indebtedness” below for additional detail. We evaluated whether there are conditions or events, considered in the aggregate, that raise substantial doubt about our ability to continue as a going concern.
We evaluated whether there are conditions or events, considered in the aggregate, that raise substantial doubt about our ability to continue as a going concern.
These agreements generally provide for non-refundable upfront license fees, development and commercial performance milestone payments, cost sharing, royalty payments and/or profit sharing.
These agreements generally provide for non-refundable upfront license fees, development and commercial performance milestone payments, cost sharing, royalty payments and/or profit sharing. We have also licensed rights to our legacy biosimilar product candidates (ONS-3010, ONS-1045 and ONS-1050) in other markets.
The decrease was primarily due to BLA submission fees of $6.2 million paid in the prior period that were subsequently waived and refunded by the FDA in the current period, $0.9 million decrease in ONS 5010 development costs in the current period, and a decrease in stock-based compensation expenses of $1.7 million primarily due to vesting of performance-based stock options for some of our executives in the prior period. 83 Table of Contents General and Administrative Expenses The following table summarizes our general and administrative expenses by type for the years ended September 30, 2023 and 2022: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year ended September 30, ​ 2023 2022 Professional fees ​ $ 14,522,528 ​ $ 8,637,887 Compensation and related benefits ​ ​ 4,366,447 ​ ​ 4,102,783 Stock-based compensation ​ ​ 4,560,421 ​ ​ 5,019,474 Facilities, fees and other related costs ​ ​ 3,224,044 ​ ​ 2,979,753 Total general and administrative expenses ​ $ 26,673,440 ​ $ 20,739,897 ​ General and administrative expenses for the year ended September 30, 2023 increased by $5.9 million compared to the year ended September 30, 2022.
The 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.
We do not believe our existing cash and cash equivalents as of September 30, 2023 of $23.4 million are sufficient to fund our operations through one year from the Form 10-K filing date as a result of the costs associated with initiating the planned NORSE EIGHT clinical trial and the April 1, 2024 maturity date of the December 2022 Note, as amended in December 2023.
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.
Our future operations are highly dependent on a combination of factors, including (i) the timely and successful completion of additional financing discussed above, (ii) our ability to complete revenue-generating partnerships with pharmaceutical companies, (iii) the success of our research and development, (iv) the development of competitive therapies by other biotechnology and pharmaceutical companies, and, ultimately, (v) regulatory approval and market acceptance of our proposed future products. 86 Table of Contents Cash Flows The following table summarizes our cash flows for each of the years presented: ​ ​ ​ ​ ​ ​ ​ ​ ​ ​ Year ended September 30, ​ 2023 2022 Net cash used in operating activities ​ $ (42,973,398) ​ $ (56,674,559) Net cash provided by financing activities ​ ​ 48,968,568 ​ ​ 59,594,047 Net increase in cash and cash equivalents ​ $ 5,995,170 ​ $ 2,919,488 ​ Operating Activities 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.
Our future operations are highly dependent on a combination of factors, including (i) the timely and successful completion of additional financing discussed above, (ii) our ability to complete revenue-generating partnerships with pharmaceutical companies, (iii) the success of our research and development, (iv) the development of competitive therapies by other biotechnology and pharmaceutical companies, and, ultimately, (v) regulatory approval and market acceptance of our proposed future products.
The FDA is expected to respond to the SPA in early February 2024. We have received agreement from the FDA on three SPAs for three additional registration clinical trials for our ongoing Phase 3 program for ONS-5010.
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.
Loss on equity method investment Loss on equity method investment represents our proportionate share for the period of the net loss of our investee to which the equity method of accounting is applied. 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.
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.
Wainwright & Co., as sales agent (“Wainwright”), (the “Wainwright ATM Agreement” or the “Wainwright ATM Offering”), under which we could issue and sell shares of our common stock having an aggregate offering price of up to $40,000,000 from time to time through Wainwright.
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.
We also made $10.2 million in debt and finance lease obligation payments and a $0.8 million payment of financing costs.
We also made $10.2 million in debt and finance lease obligation payments and a $0.8 million payment of financing costs. Description of Indebtedness The December 2022 Note contains customary covenants, including a restriction on the Company’s ability to pledge certain of the Company’s assets, subject to certain exceptions, without the Lender’s consent.
We do not believe our current cash resources of $23.4 million are sufficient to fund our operations through one year from the Form 10-K filing date as a result of the costs associated with initiating the planned NORSE EIGHT clinical trial and the April 1, 2024 maturity date of the December 2022 Note, as amended in December 2023.
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.

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