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Item 1. Business

2026-02-05 compared with 2025-03-03 · 462 added, 373 removed, 1154 unchanged (42% of the section changed)

We are a biopharmaceutical company committed to redefining the retina experience.

AXPAXLI (axitinib intravitreal hydrogel, also known as OTX-TKI), our product candidate for retinal disease, is based on our proprietary ELUTYX bioresorbable hydrogel-based formulation technology.

AXPAXLI is currently in two repeat-dosing Phase 3 clinical trials for the treatment of wet age-related macular degeneration, or wet AMD, which we refer to as the SOL-1 and the SOL-R trials.

We have also completed a Phase 1 clinical trial of AXPAXLI for the treatment of non-proliferative diabetic retinopathy, or NPDR, which we refer to as the HELIOS trial.

We intend to meet with the U.S.

Food and Drug Administration, or FDA, in the first half of 2025 to discuss the design of a potential registrational clinical program for AXPAXLI for the treatment of NPDR and diabetic macular edema, or DME, and then evaluate our next steps.

We also leverage the ELUTYX technology in our commercial product DEXTENZA, an FDA-approved corticosteroid for the treatment of ocular inflammation and pain following ophthalmic surgery and for the treatment of ocular itching associated with allergic conjunctivitis, and our product candidate PAXTRAVA (travoprost intracameral hydrogel, also known as OTX-TIC), which is currently in a Phase 2 clinical trial for the treatment of open-angle glaucoma, or OAG, or ocular hypertension, or OHT.

We are an integrated biopharmaceutical company committed to redefining the retina experience.

AXPAXLI, also known as OTX-TKI, our investigational product candidate for retinal disease, is an axitinib intravitreal hydrogel based on our ELUTYX proprietary bioresorbable hydrogel-based formulation technology.

AXPAXLI is currently being evaluated in a Phase 3 registrational program for wet age-related macular degeneration, or wet AMD, which we refer to as the SOL program.

AXPAXLI is currently also being evaluated in a Phase 3 registrational program for diabetic retinal disease, including non-proliferative diabetic retinopathy, or NPDR, which we refer to as the HELIOS program.

We also leverage the ELUTYX technology in our commercial product DEXTENZA, a corticosteroid approved by the U.S.

Food and Drug Administration, or FDA, for the treatment of ocular inflammation and pain following ophthalmic surgery in adults and pediatric patients and for the treatment of ocular itching associated with allergic conjunctivitis in adults and pediatric patients aged two years or older, and in our product candidate OTX-TIC, which is a travoprost intracameral hydrogel that has completed a Phase 2 clinical trial for the treatment of open-angle glaucoma, or OAG, or ocular hypertension, or OHT.

We are currently evaluating next steps for the OTX-TIC program.

DEXTENZA and our product candidates in clinical development generally incorporate therapeutic agents that have previously received regulatory approval from the FDA, including small molecules, into ELUTYX, with the goal of providing local programmed release to tailor the duration and amount of the therapeutic agent to be delivered to the eye.

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As a result, we believe that the ELUTYX technology is well tolerated.

We believe the ELUTYX technology can provide delivery solutions for durable therapies for wet AMD, NPDR, DME, proliferative diabetic retinopathy, or PDR, retinal vein occlusion, or RVO, and other diseases and conditions of the eye, such as glaucoma.

We believe the ELUTYX technology can provide delivery solutions for durable therapies for wet AMD, diabetic retinal disease, including NPDR, diabetic macular edema, or DME, and proliferative diabetic retinopathy, or PDR, retinal vein occlusion, or RVO, and other diseases and conditions of the eye, such as glaucoma.

Our ELUTYX-based products and product candidates are hydrogels with ester bonds that are hydrolyzed over time by aqueous or vitreous humor fluid within the eye.

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AXPAXLI is seeking to address segments of the exudative retinal diseases market, which in the aggregate is estimated to include up to 8.3 million patients in the United States by 2030 and accounted for approximately $9.4 billion in U.S.

annual estimated revenues in 2024, according to the Market Scope 2024 Retinal Pharmaceuticals Market Report:

Wet AMD and Other Exudative Diseases, published in September 2024, or the “Market Scope 2024 Retina Report.

annual estimated revenues in 2025, according to the Market Scope 2025 Exudative Retinal Disease Pharmaceuticals Report, published in October 2025, or the Market Scope 2025 Retina Report.

The following table summarizes the status of our key product candidates and development programs.

We hold worldwide exclusive commercial rights to the core technology underlying all of our product candidates in development and have not granted commercial rights to any marketing partners other than a license agreement and collaboration with AffaMed Therapeutics Limited, or AffaMed, for the development and commercialization of DEXTENZA and PAXTRAVA in certain geographies in Asia agreed to between the parties.

We hold worldwide exclusive commercial rights to the core technology underlying all of our product candidates in development and have not granted commercial rights to any marketing partners other than a license agreement and collaboration with AffaMed Therapeutics Limited, or AffaMed, for the development and commercialization of DEXTENZA and OTX-TIC in certain geographies in Asia agreed to between the parties.

PIPELINE AT A GLANCE

Our strategy is to advance our pipeline of clinical assets, focusing specifically on our programs for wet AMD as well as NPDR and DME, while we continue to build upon our experience in commercializing ophthalmology products.

Our strategy is to redefine the retina experience by advancing AXPAXLI, our lead clinical asset, focusing specifically on our registrational programs for wet AMD and diabetic retinal disease, while we continue to build upon our experience in commercializing ophthalmology products.

The key tactics of our strategy are:

● Advance our AXPAXLI clinical development programs.

Continue the SOL-1 trial, as amended to incorporate re-dosing, and report topline data on the primary efficacy endpoint in the first quarter of 2026.

Complete enrollment and randomization of the SOL-R trial expeditiously.

● NPDR and DME:

Seek FDA feedback in the first half of 2025 to discuss the design of a potential registrational clinical program and then evaluate our next steps.

● Advance our AXPAXLI registrational programs.

● Continue the SOL-1 Phase 3 clinical trial and expect to present 52 Week results at the 49th Macula Society Annual Meeting, taking place between February 25 – 28, 2026.

All subjects have completed their Week 52 visit and have been re-dosed according to their baseline treatment assignment.

● Obtain additional clinical data from the continuation of the SOL-1 trial through the end of Week 104 and the continuation of the SOL-R Phase 3 clinical trial, for which we intend to report topline data on the primary efficacy endpoint in the first quarter of 2027, and the planned SOL-X trial, which we intend to initiate in the second quarter of 2026.

● Pending the receipt of favorable results from the SOL-1 trial and planned interactions with the FDA, we intend to submit a new drug application, or NDA, for AXPAXLI for the treatment

of wet AMD based on SOL-1 Week 52 data.

We also plan to leverage the 505(b)(2) approval pathway, which could potentially shorten the NDA review timeline for AXPAXLI by up to two months.

● Diabetic Retinal Disease:

● We plan to target a broad label in diabetic retinal disease by conducting the HELIOS registrational program in patients with moderately severe to severe NPDR and including subjects in the program who also have non-center-involved DME, or non-CI-DME, in addition to NPDR.

We plan to refine our development plans and registration strategy for AXPAXLI for the treatment of diabetic retinal disease based on our anticipated discussions with the FDA regarding the regulatory pathway for AXPAXLI for the treatment of wet AMD.

● Scale up our commercialization and manufacturing capabilities.

● Initiate activities to build on our existing sales, marketing and distribution capabilities, which we currently use to market DEXTENZA, to prepare for potential commercialization of AXPAXLI for the treatment of wet AMD as well as NPDR and DME.

● Build out and validate our manufacturing operations in our existing facilities.

We will evaluate our next steps for PAXTRAVA for the treatment of OAG or OHT once we have completed the Phase 2 clinical trial for this program.

Limitations of Back-of-the-Eye Injections

An intravitreal injection is a procedure to place a medication directly into the space in the back of the eye called the vitreous cavity, which is filled with a jelly-like fluid called the vitreous humor gel.

The procedure is usually performed by a trained retina specialist in the office setting.

Intravitreal injections are used to administer medications to treat a variety of chronic conditions;

wet AMD, DR, DME, and RVO, are among the most common conditions treated with intravitreal drugs.

The most common intravitreal injections are anti-VEGF (vascular endothelial growth factor, or VEGFs) drugs.

Anti-VEGF drugs and steroids, which also can be injected intravitreally, help to reduce fluid leakage associated with these disorders.

While anti-VEGF treatment regimens can be very effective therapies, there are a number of significant drawbacks, driven primarily by the frequency of injections.

Patients typically require injections every six to eight weeks, but can require them as frequently as every 4 weeks.

We refer to the number of injections a patient has over a given time period as the treatment burden of the particular treatment.

The actual injection at the time of administration is often uncomfortable for patients and can be a deterrent in terms of compliance.

Then there is the burden to both patients and their caregivers of regular office visits.

These patients may not be mobile enough to travel to the office on their own and therefore require not only the assistance of a caregiver but also transportation to and from the office.

These patients may also be younger, part of the active workforce and therefore unwilling or unable to take personal time off to receive frequent injections.

Furthermore, frequent injections of medications to the back of the eye can lead to peaks and troughs of medication levels, with fluctuations of intraretinal fluid based on these levels.

Such fluid fluctuations have been associated with decreased vision and possibly fibrosis.

Finally, while intravitreal injections are typically safe, there is the potential risk of endophthalmitis (infection in the eye), inflammation, bleeding into the vitreous gel and retinal detachment that comes with injections.

As a result of these limitations, there is a significant unmet need for technologies that will allow for a longer duration of effect and an overall reduced treatment burden, measured by the number of injections.

● Invest in infrastructure, including capital expenditures, to support initial expected commercial production levels of AXPAXLI, including continuing our efforts to transform our existing manufacturing facility at 15 Crosby Drive in Bedford, Massachusetts into a commercial manufacturing facility, and the build out of manufacturing processes for the device that is used to administer AXPAXLI to the eye together with third party contract manufacturing organizations, or CMOs.

● Advance pre-commercialization activities associated with AXPAXLI.

● Continue and accelerate activities to expand our existing sales, marketing and distribution capabilities, currently used to market DEXTENZA, to prepare for commercialization of AXPAXLI, if approved, for the treatment of wet AMD as well as for diabetic retinal disease.

Clinical Portfolio

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If untreated, neovascularization in wet AMD patients typically results in formation of a scar under the macular region of the retina.

The current standard of care for wet AMD is treatment with drugs that target VEGF, one of several proteins involved in neovascularization and hyper-permeability of established and new blood vessels.

The current standard of care for wet AMD is treatment with drugs that target vascular endothelial growth factor, or VEGF, one of several proteins involved in neovascularization and hyper-permeability of established and new blood vessels.

Wet AMD is the most common cause of visual impairment among patients over the age of 50 years in developed countries.

According to the Market Scope 2024 Retina Report, there were approximately 1.7 million people in the United States who suffered from wet AMD in 2024.

This population is expected to grow at a 3.2% compound annual growth rate, or CAGR, through 2029.

The anti-VEGF market for the treatment of wet AMD consists predominantly of four drugs that are approved for marketing and primarily prescribed for the treatment of wet AMD:

According to the Market Scope 2025 Retina Report, there were approximately 14.8 million people globally and 1.7 million people in the United States who suffered from wet AMD in 2025, and this population is expected to grow at a 3.0% and 3.3% compound annual growth rate, or CAGR, respectively, through 2030.

The market for the treatment of wet AMD consists predominantly of five anti- VEGF, drugs, including four drugs that are approved for marketing and primarily prescribed for the treatment of wet AMD:

Eylea and Eylea HD, marketed in the United States by Regeneron;

Lucentis, marketed in the United States by Genentech;

and Vabysmo, marketed in the United States by Genentech.

Bevacizumab, also known as Avastin, an anti-VEGF therapy approved for the treatment of certain cancers, is also used off-label in ophthalmology.

Non-Proliferative Diabetic Retinopathy (NPDR) and Diabetic Macular Edema (DME)

Diabetic retinopathy, or DR, is a progressive condition in which chronically elevated levels of blood glucose lead to damage of the tiny blood vessels in the retina.

DR is among the most common microvascular complications of diabetes, making diabetes the leading cause of new cases of blindness in adults.

DR can take time to develop.

NPDR, which is an early stage of DR and sometimes called background retinopathy, is often asymptomatic and may go unnoticed until it is very advanced with vision loss imminent.

PDR is the most serious stage of the disease that develops when areas of the retina are starved for nourishment and oxygen, triggering the proliferation of new blood vessels via secretions of growth factors including VEGFs.

These new blood vessels can bleed or lead to tractional retinal detachments, or both, and permanent vision loss.

Another visual threatening complication of DR is DME where the damaged blood vessels leak blood and fluid into the retina.

The current standard of care for DR at the non-proliferative stage is watchful waiting, with the use of anti-VEGFs or steroids when the disease has progressed to center-involved DME, or CI-DME, or the proliferative stage.

In addition, laser treatment can be used to manage DR.

Vabysmo, marketed in the United States by Genentech, and one drug, bevacizumab, also known as Avastin, an anti-VEGF therapy approved for the treatment of certain cancers, which is used off-label for the treatment of wet AMD.

Diabetic Retinal Disease

Diabetic retinal diseases are an increasingly prevalent global health concern, driven by the rapidly rising number of individuals diagnosed with diabetes each year.

Diabetic retinopathy, or DR, is the most common category of retinal diseases, affecting over an estimated 103 million people worldwide.

DR is a progressive condition in which retinal blood vessels are damaged following a cascade of events triggered by chronically elevated levels of blood glucose.

As many as half of all diabetic patients are expected to develop some form of DR in their lifetime.

DR can progress from the non-proliferative stages, or the NPDR stages, to the proliferative stage, or the PDR stage, characterized by the growth of abnormal new blood vessels.

The severity of DR is commonly assessed using an objective severity score based on graded retinal images, which is referred to as the diabetic retinopathy severity score, or DRSS.

Based on third-party market research data, we estimate that fewer than 1% of the 6.3 million NPDR patients in the U.S.

receive treatment today, despite the availability of anti-VEGF therapies approved for the indication, largely due to the burden of frequent injections.

DME is also a leading cause of vision loss in the working-age population.

DME, the result of an accumulation of fluid in the macula that can afflict patients with diabetes, can occur at any stage of DR.

In patients with DME, blood vessels in the eyes leak and bleed, and the retina starts to swell, which can cause vision loss or blindness.

Anti-VEGF drugs are approved to treat DME, but these treatments typically require frequent intravitreal injections, placing a significant burden on patients and physicians alike.

It is estimated that there were 6.3 million cases of NPDR and 1.7 million cases of DME in the United States in 2025 according to the Market Scope 2025 Retina Report, growing at a CAGR of 1.7% and 1.8%, respectively, through 2030.

The anti-VEGF market for the treatment of DR consists predominantly of three drugs that are approved for marketing, although only sparingly used for the treatment of DR:

Lucentis, Eylea, and Eylea HD.

The anti-VEGF market for the treatment of diabetic retinal disease consists predominantly of four drugs that are approved for different diabetic retinal disease indications (Lucentis, Eylea, Eylea HD, and Vabysmo).

Avastin is also used off-label for the treatment of diabetic retinal disease.

Retinal Programs

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AXPAXLI is delivered by intravitreal injection and is designed for a duration of six months or longer.

Our wet AMD registrational program for AXPAXLI is comprised of two ongoing complementary clinical trials, SOL-1 and SOL-R, which are strategically designed with the intent of de-risking subject populations, aligning with regulatory standards, and providing a broad evaluation of AXPAXLI’s durability, repeatability, and flexibility.

We have also conducted a Phase 1 clinical trial in Australia and a Phase 1 clinical trial in the United States to evaluate AXPAXLI for the treatment of wet AMD.

We have completed the HELIOS trial to evaluate AXPAXLI for the treatment of NPDR.

We intend to meet with the FDA in the first half of 2025 to discuss the design of a potential registrational clinical program for AXPAXLI for the treatment of NPDR and DME and then evaluate our next steps.

We believe axitinib is well-suited for use with our platform given its high potency, multi-target capability, and compatibility with a hydrogel vehicle.

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We believe ELUTYX gives us potential advantages to address all three of these challenges.

Our initial hydrogel implants have delivered anti-VEGF compounds in vitro over a targeted nine-to-twelve-month period, which we believe could make it possible to reduce patients’ treatment burden by reducing the frequency of the current monthly or bi-monthly intravitreal injection regimen for wet AMD.

Our prolonged constant rate of axitinib delivery over a nine-to-twelve-month period could make it possible to reduce patients’ treatment burden by reducing the frequency of treatment for wet AMD.

We conducted the two Phase 1 trials of AXPAXLI for the treatment of wet AMD with different formulations of axitinib.

We are conducting the SOL-1 and SOL-R trials with a single 450 µg axitinib dose of AXPAXLI, which is a different formulation than we used in either of the two Phase 1 trials of AXPAXLI for the treatment of wet AMD.

This optimized configuration is expected to provide for an increased daily release of the drug and is designed to improve synchronization of axitinib drug release with hydrogel bioresorption.

The two Phase 1 trials of AXPAXLI for the treatment of wet AMD, the HELIOS trial, and the initial portions of the SOL-1 and SOL-R trials were conducted with a two-piece injector.

We have developed a next-generation one-piece injector which we believe improves the administration of AXPAXLI to the eye.

We expect to use this one-piece injector for the administration of AXPAXLI in a majority of the subjects in the AXPAXLI arm of the SOL-R trial and for the repeat-dosing of AXPAXLI in all subjects in the AXPAXLI arm of the SOL-1 trial.

We are currently conducting the SOL-1, SOL-R and HELIOS-3 trials, and we plan to conduct the SOL-X trial and, if needed, the HELIOS-2 trial with a 450 µg axitinib dose of AXPAXLI, or AXPAXLI 450 µg, which is a different formulation than we used in either of the two Phase 1 trials of AXPAXLI that we have completed for the treatment of wet AMD.

This optimized configuration provides for an increased daily release of the drug and improved synchronization of axitinib drug release with hydrogel bioresorption.

Wet Age-Related Macular Degeneration (Wet AMD)

In addition, in the second quarter of 2026, we plan to initiate a long-term extension study, which we refer to as the SOL-X trial, to evaluate the long-term safety of AXPAXLI;

to explore long-term visual outcomes, including visual acuity and the incidence and/or progression of fibrosis and macular atrophy;

and to evaluate the impact of delayed initiation of AXPAXLI in patients who initially were randomized to receive aflibercept in either SOL-1 or SOL-R.

We have also conducted a Phase 1 clinical trial in Australia and a Phase 1 clinical trial in the United States to evaluate AXPAXLI for the treatment of wet AMD.

The SOL-1 Trial

We are currently conducting the SOL-1 trial, a repeat-dosing registrational Phase 3 clinical trial for the treatment of wet AMD.

The SOL-1 trial is designed as a prospective, multi-center, randomized, parallel-group trial that involves more than 100 trial sites located in the United States and Argentina.

The SOL-1 trial is designed as a superiority trial comparing a single optimized dose of AXPAXLI with a drug load of 450 µg of axitinib to a single injection of aflibercept 2 mg and assessing the safety and efficacy of AXPAXLI in subjects with wet AMD.

The SOL-1 trial is designed as a prospective, multi-center, double-masked, randomized (1:1), parallel-group, two-arm superiority trial that involves more than 100 trial sites located in the United States and Argentina.

The SOL-1 trial is designed as a superiority trial comparing a single injection of AXPAXLI 450 µg to a single injection of aflibercept 2 mg and assessing the safety and efficacy of AXPAXLI in subjects with wet AMD.

The primary endpoint is the proportion of subjects who maintain visual acuity, defined as a Best Corrected Visual Acuity, or BCVA, loss of fewer than 15 letters on the Early Treatment of Diabetic Retinopathy Study, or ETDRS, letters chart from baseline at Week 36.

This superiority trial has an 8-week loading segment with two monthly aflibercept 2 mg intravitreal injections prior to randomization, thereafter a 52-week masked treatment segment, and a 52-week safety follow-up with re-dosing

at Weeks 52 and 76.

The design of the SOL-1 trial enhances the potential for a 6 - 12 month dosing label for AXPAXLI for the treatment of wet AMD and also provides insights into the long-term durability of AXPAXLI.

The SOL-1 trial is intended to randomize approximately 300 evaluable treatment-naïve subjects with a diagnosis of wet AMD in the study eye with good visual acuity and a diagnosis of macular choroidal neovascularization at screening.

The SOL-1 trial completed randomization of 344 subjects in December 2024.

One of the secondary endpoints being evaluated is the proportion of subjects who maintain visual acuity measured at Week 52.

At Weeks 52 and 76, all subjects that were randomized in the trial at Day 1, including subjects who previously received supplemental anti-VEGF treatment, are re-dosed with their respective initial treatment of a single injection of AXPAXLI 450 μg in the investigational arm or a single injection of aflibercept 2 mg in the control arm.

Subjects will be followed for safety until the end of Week 104.

We believe the design of the SOL-1 trial enhances the potential for a 6 - 12 month dosing label for AXPAXLI for the treatment of wet AMD and also provides insights into the long-term durability of AXPAXLI.

In December 2024, the SOL-1 trial completed randomization of 344 evaluable treatment-naïve subjects with a diagnosis of wet AMD in the study eye who have 20/80 vision or better and a central subfield thickness, or CSFT, of not more than 500 µm.

Under the study protocol, after initial screening, every enrolled subject received two aflibercept 2 mg loading doses between the screening visit and Day 1:

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Throughout the trial, subjects are assessed monthly.

Subjects who failed randomization became eligible to be screened for the SOL-R trial.

Subjects who were successfully randomized in the SOL-1 trial on Day 1 are being followed every month and will receive a supplemental dose of aflibercept 2 mg as needed based on pre-specified criteria.

Our pre-specified rescue criteria are a loss of 15 or more letters on the ETDRS chart compared to baseline due to wet AMD, or a new hemorrhage that is deemed to be likely to cause irreversible vision loss due to progression of wet AMD.

The first time a subject is observed to have lost 15 or more ETDRS letters in BCVA in the study eye due to wet AMD at any time in the trial would be considered as having met the endpoint as a treatment failure.

We are conducting the SOL-1 trial in accordance with a Special Protocol Assessment, or SPA, agreement with the FDA.

We initially sought an SPA agreement from the FDA to determine whether the proposed clinical protocol and the statistical analysis plan for the SOL-1 trial adequately addressed scientific and regulatory requirements for a clinical trial that could support a marketing application.

The first time a subject is observed to have lost 15 or more ETDRS letters in BCVA in the study eye due to wet AMD at any time up to Week 36 in the trial would be considered as having met the endpoint as a treatment failure.

We are conducting the SOL-1 trial in accordance with a SPA agreement with the FDA.

We initially sought a SPA agreement from the FDA to determine whether the proposed clinical protocol and the statistical analysis plan for the SOL-1 trial adequately addressed scientific and regulatory requirements for a clinical trial that could support a marketing application.

We received an agreement letter regarding the overall trial design from the FDA under the SPA agreement on October 30, 2023.

In December 2023, we submitted a first SPA agreement modification to the FDA to broaden the inclusion criteria for subjects in the SOL-1 trial and to reflect our intention to evaluate a single optimized dose of AXPAXLI with a drug load of 450 µg of a more soluble form of axitinib in the trial.

In December 2023, we submitted a first SPA agreement modification to the FDA to broaden the inclusion criteria for subjects in the SOL-1 trial and to reflect our intention to evaluate a single optimized dose of AXPAXLI 450 μg of a more soluble form of axitinib in the trial.

We received an agreement letter regarding the first SPA agreement modification from the FDA on January 22, 2024.

This first SPA agreement modification enabled us to include in the trial treatment-naïve wet AMD subjects with visual acuity of approximately 20/80 or better at the initial screening visit.

This first SPA agreement modification enabled us to include

in the trial treatment-naïve wet AMD subjects with visual acuity of approximately 20/80 or better at the initial screening visit.

These subjects then needed to reach the BCVA of approximately 20/20 or experience an improvement of at least 10 ETDRS letters gain from the initial screening visit at Day 1 to be randomized.

In addition, the subjects were stratified between the two treatment groups at randomization based on BCVA category (≤ 71 and >71 ETDRS letters) as of the initial screening visit.

In January 2025, we submitted a second SPA agreement modification to the FDA to add a repeat dose of AXPAXLI 450 µg at Week 52 and at Week 76, in each case, after all pre-defined efficacy endpoint assessments, to generate the required safety data for subjects re-dosed with AXPAXLI through Week 104, to support long-term dosing.

In January 2025, we submitted a subsequent SPA agreement modification to the FDA to add a repeat dose of AXPAXLI 450 µg at Week 52 and at Week 76, in each case, after all pre-defined efficacy endpoint assessments, to generate the required safety data for subjects re-dosed with AXPAXLI 450 μg through Week 104, to support long-term dosing.

We received an agreement letter regarding the second SPA agreement modification from the FDA on February 24, 2025.

As of March 3, 2025, subject retention in the SOL-1 trial has been exceptional, and the vast majority of rescue treatments, reviewed on a masked basis, have been in accordance with pre-specified criteria under the trial protocol.

Because the inclusion of re-dosing requires all data to be masked until week 52, we now expect topline results for SOL-1 to be available in the first quarter of 2026.

As of February 4, 2026, the SOL-1 trial continues to maintain an exceptional rate of subject retention and per protocol-defined treatment rescues.

All subjects have completed their Week 52 visit and have been re-dosed according to their baseline treatment assignment.

Oversight by an independent data and safety monitoring committee has not identified any safety signals in the SOL-1 trial to date.

As of February 4, 2026, the results of the SOL-1 trial remain masked.

We expect to present Week 52 results for the SOL-1 trial at the 49th Macula Society Annual Meeting, taking place between February 25 – 28, 2026.

The SOL-R Trial

In June 2024, we initiated the SOL-R trial, a repeat-dosing registrational Phase 3 clinical trial for the treatment of wet AMD.

The SOL-R trial is designed as a multi-center, double-masked, randomized (2:2:1), three-arm trial that will involve sites located in the U.S.

and the rest of the world.

The trial is intended to randomize approximately 555 subjects that are either treatment naïve or have been diagnosed with wet AMD in the study eye within the prior four months and received up to three monthly anti-VEGF injections with last injection approximately 4 weeks prior to screening for SOL-R.

Prior to the second SPA amendment and inclusion of re-dosing in SOL-1 as described above, we previously intended to randomize 825 subjects in the SOL-R trial.

This non-inferiority trial reflects a patient enrichment strategy over the six months prior to randomization that includes five loading doses of anti-VEGF therapy, including aflibercept 2 mg, and monitoring to exclude those subjects with significant retinal fluid fluctuations.

In the first arm, subjects will receive a 450 µg dose of AXPAXLI at Day 1 and be re-dosed at Weeks 24, 48, and every 24 weeks thereafter.

In the second arm,

subjects will receive aflibercept 2 mg on-label every 8 weeks.

In the third arm, subjects will receive an 8 mg dose of aflibercept (Eylea HD) at Day 1 and will be re-dosed at Weeks 24, 48, and every 24 weeks thereafter, aligned with the AXPAXLI dosing regimen in the first arm and serving as adequate masking pursuant to current FDA guidance.

The SOL-R trial is designed as a multi-center, double-masked, randomized (2:2:1), three-arm trial that involves sites located in the U.S., Argentina, India and Australia.

This non-inferiority trial sought to enroll subjects that were either treatment naïve or had been diagnosed with wet AMD in the study eye within the prior four months.

The trial design reflects a patient enrichment strategy over the six months prior to randomization that includes three screening and two loading doses of anti-VEGF therapy, including aflibercept 2 mg, and monitoring to exclude those subjects with early persistent fluid, showing CSFT of more than 350 microns, or significant retinal fluid fluctuations, showing CSFT increase of 35 microns or more from the lowest CSFT measurement at any prior visit.

In the first arm, subjects will receive a dose of AXPAXLI 450 µg at Day 1 and be re-dosed with AXPAXLI 450 μg at Weeks 24, 48, and every 24 weeks thereafter.

In the second arm, subjects will receive aflibercept 2 mg on-label every 8 weeks.

In the third arm, subjects will receive an 8 mg dose of aflibercept at Day 1 and will be re-dosed at Weeks 24, 48, and every 24 weeks thereafter, aligned with the AXPAXLI dosing regimen in the first arm and serving as adequate masking pursuant to current FDA guidance.

Subjects will be followed for safety until Week 96.

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The clinical trial protocol requires that, during the trial, subjects in any arm meeting pre-specified rescue criteria will receive a supplemental dose of aflibercept 2 mg.

The pre-specified rescue criteria include a loss of 10 or more ETDRS letters in BCVA from baseline or a combination of worsening anatomical measures and BCVA loss.

The pre-specified rescue criteria include a loss of more than 5 ETDRS letters in BCVA from best recorded prior visit (baseline or later) due to wet AMD, combined with an increase of 75 microns or more in CSFT from prior lowest measurement (baseline or later) due to wet AMD.

The primary endpoint is non-inferiority in mean change in BCVA from baseline between the AXPAXLI and on-label aflibercept 2 mg arms at Week 56.

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The first subject was enrolled in the SOL-R trial in July 2024.

Initially, subjects screened and enrolled in the SOL-R trial included only subjects that constituted loading or randomization failures from the SOL-1 trial.

In November 2025, we announced that the SOL-R trial had achieved its randomization target of 555 subjects.

We continued to allow randomization of previously enrolled subjects that were still in the loading phase when we achieved target randomization to maintain our commitment to both patients and investigators.

We have completed randomization of the SOL-R trial with 631 subjects randomized.

We expect topline data from the SOL-R trial to be available in the first quarter of 2027, an acceleration from our previous guidance of the first half of 2027.

In a written Type C response received in August 2024, and a subsequent written response received in December 2024, the FDA agreed that the SOL-R repeat dosing wet AMD trial, with a primary endpoint at Week 56, should be appropriate as an adequate and well-controlled trial in support of a potential NDA and product label for AXPAXLI for the treatment of wet AMD.

The FDA also noted that the use of one superiority trial and one non-inferiority trial is generally acceptable as the basis of an eventual NDA in wet AMD.

On November 14, 2024, we announced that, as the SOL-1 trial neared completion of randomization, trial sites could directly screen and enroll eligible subjects into the SOL-R trial.

On January 14, 2025, we announced that, as of January 10, 2025, we had enrolled 311 subjects across various stages of loading and randomization.

All subjects that have been randomized to date have received their first 450 µg dose of AXPAXLI at Day 1 with the 2-piece injector.

At the time, the FDA also noted that the use of one superiority trial and one non-inferiority trial is generally acceptable as the basis of an eventual NDA in wet AMD.

The SOL-X Trial

We plan to initiate a multi-center, open-label long-term safety extension clinical trial, which we refer to as the SOL-X trial, in the second quarter of 2026 to evaluate subjects who have completed their two-year safety follow-up visits in either the SOL-1 or SOL-R trials for an additional three years.

The primary objectives of the planned SOL-X trial are to evaluate the long-term safety of AXPAXLI;

to explore long-term visual outcomes, including visual acuity and the incidence and/or progression of fibrosis and macular atrophy;

and to evaluate the impact of delayed initiation of AXPAXLI in patients who initially were randomized to receive aflibercept in either SOL-1 or SOL-R.

According to the planned trial design, subjects enrolled in the SOL-X trial are to receive AXPAXLI 450 μg every 24 weeks and are to be evaluated at Week 4, Week 12, and every 12 weeks thereafter.

Phase 1 Clinical Trial (Australia)

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In cohort 3b (400 µg dose plus anti-VEGF induction injection of aflibercept), two subjects showed a decrease in intraretinal or subretinal fluid as early as a week after treatment.

We observed extended duration of activity of six months or more for over 60% of subjects across all cohorts and for over 80% of subjects in cohort 3a, in which we administered a 600 μg

We observed extended duration of activity of six months or more for over 60% of subjects across all cohorts and for over 80% of subjects in cohort 3a, in which we administered a 600 μg dose.

In addition, the AXPAXLI doses in cohort 1 (200 µg single dose) were observed to have biodegraded in all subjects within nine to 10.5 months of injection.

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Phase 1 Clinical Trial (United States)

We have conducted a prospective, multi-center, randomized, controlled Phase 1 clinical trial in the United States under an exploratory investigational new drug, or eIND, application to evaluate a single 600 µg dose of AXPAXLI with an anti-VEGF injection in comparison with a 2 mg dose of aflibercept.

We have conducted a prospective, multi-center, randomized, controlled Phase 1 clinical trial in the United States to evaluate a single 600 µg dose of AXPAXLI with an anti-VEGF injection in comparison with a 2 mg dose of aflibercept.

This trial was initiated under an exploratory investigational new drug, or eIND, application, and subsequently transitioned to a traditional investigational new drug, or IND, application.

The population we studied in this U.S.-based clinical trial was different than the population we studied in our Phase 1 clinical trial of AXPAXLI in Australia.

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Overall, an 89% reduction in treatment burden was observed in AXPAXLI treated subjects at 12 months.

These results align with our expectation that we would see a reactivation of disease in some subjects, which we believe indicates that AXPAXLI continues to function as designed with axitinib concentrations beginning to fall below therapeutic levels after the hydrogel bioresorbs.

These results align with our expectation that we would see a reactivation of

disease in some subjects, which we believe indicates that AXPAXLI continues to function as designed with axitinib concentrations beginning to fall below therapeutic levels after the hydrogel bioresorbs.

In the clinical trial, intravitreal administration of single AXPAXLI 600 µg dose was generally well tolerated during the 52 weeks of the study.

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Furthermore, there were fewer injections over 52 weeks received in subjects from AXPAXLI treatment compared to those received in aflibercept 2 mg treatment arm.

If we were to obtain favorable results from the SOL-1 and the SOL-R trials evaluating AXPAXLI for the treatment of wet AMD, we expect that we would submit an NDA under Section 505(b)(2) of the FDCA.

See “—Government Regulation—Section 505(b)(2) NDAs” for additional information.

Non-Proliferative Diabetic Retinopathy (NPDR)

Phase 1 Clinical Trial

We have completed the HELIOS trial, a U.S.-based, multicenter, double-masked, randomized, parallel group Phase 1 clinical trial evaluating the safety, tolerability and efficacy of a single injection of an AXPAXLI 600 µg dose in subjects with moderately severe to severe NPDR without CI-DME.

We conducted the HELIOS trial initially under an exploratory IND, which was subsequently converted to a traditional IND.

Pending the receipt of favorable results from the SOL-1 trial and planned interactions with the FDA, we intend to submit an NDA for AXPAXLI for the treatment of wet AMD based on Week 52 data from the SOL-1 trial, without necessarily waiting to receive additional clinical data from SOL-1, SOL-R or other clinical trials.

Because axitinib is FDA-approved for non-ophthalmic indications, we plan to submit an NDA under Section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act, or FDCA, which has the potential to shorten the review timeline for AXPAXLI by up to two months compared to the traditional review pathway for new molecular entities (see “—Government Regulation—Section 505(b)(2) NDAs” for additional information).

Diabetic Retinal Disease

We commenced our HELIOS registrational program for AXPAXLI for the treatment of diabetic retinal disease with the initiation of the Phase 3 HELIOS-3 superiority clinical trial for the treatment of NPDR in November 2025.

Our potential second Phase 3 trial for the treatment of diabetic retinal disease, HELIOS-2, has not yet been initiated.

Subject to the results of our anticipated discussions with the FDA regarding filing plans for AXPAXLI in wet AMD based on data from the SOL-1 trial only, we may elect to pursue a streamlined development approach in diabetic retinal disease, potentially advancing with only a single Phase 3 HELIOS-3 trial.

The HELIOS registrational program targets a broad label in diabetic retinal disease by including subjects who also have non-CI-DME, in addition to NPDR.

We have previously conducted the HELIOS-1 trial, a Phase 1 clinical trial to evaluate AXPAXLI for the treatment of NPDR, and which also included patients with non-CI-DME.

Our HELIOS registrational program employs a novel ordinal primary endpoint of 2- step change status from baseline at Week 52 on the DRSS.

Historically, DR trials have relied on binary endpoints measuring either an improvement of 2 or more steps in DRSS or the prevention of a 2 or more step DRSS worsening.

In contrast, the ordinal endpoint we use in the HELIOS program measures changes across the DRSS spectrum, including disease improvement, stability, and worsening.

These are all clinically meaningful measures for retina specialists in the context of a disease that gets progressively worse if untreated.

The use of the novel ordinal endpoint means that every patient will contribute data to the statistical analysis, allowing for a smaller trial size to achieve statistically significant outcomes relative to the size required for a binary analysis.

We believe the ordinal DRSS endpoint enables a higher probability of success with smaller, shorter, more relevant, and less expensive trials, relative to trials conducted utilizing other potential DRSS-based endpoints.

Our use of an ordinal endpoint in the HELIOS program is the first time an ordinal endpoint has been used in DR trials.

In August 2025, we received written agreement regarding the overall design of the HELIOS-2 trial, including the proposed novel ordinal endpoint and statistical analysis plan, from the FDA under a SPA agreement.

The SPA agreement for HELIOS-2 has informed our design of the HELIOS-3 trial, as both trials were designed to use the same primary endpoint.

The HELIOS-3 Trial

The ongoing HELIOS-3 trial is evaluating the safety and efficacy of AXPAXLI and is intended to randomize approximately 930 subjects with moderately severe to severe NPDR without center-involved DME, or CI-DME.

The HELIOS-3 trial is a multi-center, double-masked, randomized (1:1:1), three-arm superiority trial comparing two dosing regimens of AXPAXLI 450 μg to a sham comparator.

The trial is expected to include subjects with non-CI-DME.

Eligible subjects in the HELIOS-3 trial are randomized as follows:

subjects in the first arm will receive a single injection of AXPAXLI 450 µg at Day 1 and will be re-dosed with AXPAXLI 450 µg at Week 24;

subjects in the second arm will receive a single injection of AXPAXLI 450 μg at Day 1 and a sham injection at Week 24;

and subjects in the third arm will receive sham injections at both Day 1 and Week 24.

Subjects will be assessed every three months throughout the trial, and subjects and designated trial personnel will remain masked through the end of Week 52.

The primary endpoint of the HELIOS-3 clinical trial is subjects’ ordinal 2-step DRSS change status from baseline—comparing whether subjects have experienced at least a two-step improvement, at least a two-step worsening, or less than a two-step change in either direction—assessed at Week 52.

On November 24, 2025, we announced that the first subject in the HELIOS-3 trial was randomized.

The HELIOS-2 Trial

We may decide to conduct a second Phase 3 clinical trial, HELIOS-2, to potentially provide enhanced support for a superiority label.

The HELIOS-2 trial is designed to evaluate the safety and efficacy of AXPAXLI in approximately 432 subjects with moderately severe to severe NPDR without center-involved DME, or CI-DME.

This multi-center, double-masked, superiority trial is designed to randomize subjects (1:1), in parallel-groups comparing a single injection of AXPAXLI 450 μg to a single injection of ranibizumab 0.3 mg.

We expect that this trial would also include subjects with non-CI-DME.

According to the planned trial design, eligible subjects in the HELIOS-2 trial would be randomized to receive either a single dose of AXPAXLI 450 μg or a single dose of ranibizumab 0.3 mg.

At Week 52, all subjects that were randomized in the trial would be re-dosed with their respective initial treatments.

Subjects would be assessed monthly through Year 1 and every other month thereafter for safety through the end of Year 2.

Subjects and designated trial personnel would remain masked through the end of Year 2.

The primary endpoint of the HELIOS-2 clinical trial would be identical to the primary endpoint of the HELIOS-3 trial, subjects’ ordinal 2-step DRSS change status from baseline as assessed at Week 52.

HELIOS-1 Phase 1 Clinical Trial

We have completed the HELIOS-1 trial, previously referred to as the “HELIOS” trial, a U.S.-based, multicenter, double-masked, randomized, parallel group Phase 1 clinical trial evaluating the safety, tolerability and efficacy of a single injection of an AXPAXLI 600 µg dose in subjects with moderately severe to severe NPDR without CI-DME.

We conducted the HELIOS-1 trial initially under an eIND, which was subsequently converted to a traditional IND.

We enrolled 22 subjects with diabetic retinopathy secondary to type 1 or type 2 diabetes who had not had an anti-VEGF injection in the prior 12 months or DME in the prior six months, randomized 2:1 to either a single dose of AXPAXLI containing 600 µg of axitinib or sham control.

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No subjects in either arm received rescue medication.

At week 48, six of 13 (46.2%) subjects in the AXPAXLI group experienced either a 1- or 2-step improvement in the Diabetic Retinopathy Severity Scale, or DRSS, with three of the 13 (23.1%) experiencing a 2-step improvement.

At week 48, six of 13 (46.2%) subjects in the AXPAXLI group experienced either a 1- or 2-step improvement in DRSS, with three of the 13 (23.1%) experiencing a 2-step improvement.

No subjects in the control group showed a 1-step or greater improvement at the same timepoint.

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Three of eight (37.5%) subjects in the control group developed PDR or CI-DME at the same timepoint.

On average, subjects in the AXPAXLI arm showed improvement in mean CSFT versus baseline compared to the control group, which showed worsening at the 48-week timepoint.

On average, subjects in

the AXPAXLI arm showed improvement in mean CSFT versus baseline compared to the control group, which showed worsening at the 48-week timepoint.

If we were to obtain favorable results from the HELIOS registrational program, we expect to submit a supplemental NDA with the FDA, targeting a broad label for diabetic retinal disease.

We plan to refine our development plans and planned regulatory pathway for AXPAXLI for the treatment of diabetic retinal disease based on our planned engagements with the FDA regarding the regulatory pathway for AXPAXLI for the treatment of wet AMD.

Injector for AXPAXLI

AXPAXLI is administered to the eye using a sterile single-dose injector.

All subjects in two of our Phase 1 trials of AXPAXLI, as well as most of the subjects in the SOL-1 trial and a small subset of subjects in the SOL-R trial were dosed with AXPAXLI using our two-piece injector.

We plan to continue the SOL program with the two-piece injector to support our planned regulatory application with a single registrational trial for wet AMD and, if approved, our launch of AXPAXLI.

As a future lifecycle initiative for AXPAXLI, we may continue development of a next-generation one-piece injector which was used to dose AXPAXLI to a subset of subjects in both the SOL-1 and SOL-R trials.

Glaucoma is a progressive and highly individualized disease in which elevated levels of IOP are associated with damage to the optic nerve, which results in irreversible vision loss.

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Branded products have maintained premium pricing and significant market share.

These products include Lumigan (bimatoprost) marketed by Allergan, Travatan Z (travoprost) marketed by Novartis, Tapros marketed by Santen, and recently approved Miebo ( perfluorohexyloctane ophthalmic solution) marketed by Bausch + Lomb.

These products include Lumigan (bimatoprost) marketed by Allergan, Travatan Z (travoprost) marketed by Novartis, Tapros

marketed by Santen, and recently approved Miebo (perfluorohexyloctane ophthalmic solution) marketed by Bausch + Lomb.

Commonly used generic drugs include latanoprost and timolol.

Glaucoma Program

PAXTRAVA (travoprost intracameral hydrogel)

Our product candidate PAXTRAVA is a bioresorbable hydrogel implant based on ELUTYX, incorporating travoprost, an FDA-approved PGA designed to lower elevated IOP, that is designed to be administered by a physician as an intracameral injection with an initial target duration of drug release of four to six months with a single treatment.

OTX-TIC (travoprost intracameral hydrogel)

Our product candidate OTX-TIC is a bioresorbable hydrogel implant based on ELUTYX, incorporating travoprost, an FDA-approved PGA designed to lower elevated IOP, that is designed to be administered by a physician as an intracameral injection with an initial target duration of drug release of four to six months with a single treatment.

Phase 2 Clinical Trial

We are conducting a U.S.-based Phase 2 prospective, multi-center, randomized, controlled clinical trial evaluating the safety, tolerability and efficacy of PAXTRAVA for the treatment of subjects with primary OAG or OHT under an IND.

The Phase 2 clinical trial was initially designed to include approximately 105 subjects at 15 to 20 sites between three arms of approximately 35 subjects each to evaluate two formulations of PAXTRAVA for the treatment of OAG or

OHT in subjects compared to DURYSTA.

The non-study eye of each subject receives a topical PGA daily, if not contraindicated.

The primary efficacy endpoint is measured by mean change from baseline (8 a.m., 10 a.m.

We have completed a U.S.-based Phase 2 prospective, multi-center, randomized, controlled clinical trial evaluating the safety, tolerability and efficacy of OTX-TIC for the treatment of subjects with primary OAG or OHT under an IND, which consisted of a primary study and a pilot repeat-dose sub-study.

The non-study eye of each subject received a topical PGA daily, if not contraindicated.

The primary efficacy endpoint was measured by mean change from baseline (8 a.m., 10 a.m.

and 4 p.m.) at 2, 6 and 12 weeks in diurnal IOP.

The active comparator control arm receives one injection of DURYSTA in one eye and a topical PGA daily in the non-study eye, if not contraindicated.

The active comparator control arm received one injection of DURYSTA in one eye and a topical PGA daily in the non-study eye, if not contraindicated.

We initiated the Phase 2 clinical trial in the fourth quarter of 2021 and dosed the first subject in the first quarter of 2022.

One arm in the Phase 2 clinical trial is receiving the same formulation used in cohort 2 of the Phase 1 clinical trial of PAXTRAVA that we conducted, containing a 26 µg dose of travoprost and utilizing a standard hydrogel.

The second arm was receiving the same formulation used in cohort 4 of the Phase 1 clinical trial, containing a 5 µg dose of drug and utilizing a fast-degrading hydrogel.

Due to elevations in IOP observed in six subjects approximately 12 weeks after enrollment in the PAXTRAVA 5 µg arm of the trial, we terminated enrollment in the 5 µg arm of the trial in the fourth quarter of 2022 and continued with the PAXTRAVA 26 µg and DURYSTA arms of the trial.

One arm in the Phase 2 clinical trial received the same formulation used in cohort 2 of the Phase 1 clinical trial of OTX-TIC that we conducted, containing a 26 µg dose of travoprost and utilizing a standard hydrogel.

The second arm received the same formulation used in cohort 4 of the Phase 1 clinical trial, containing a 5 µg dose of drug and utilizing a fast-degrading hydrogel.

Due to elevations in IOP observed in six subjects approximately 12 weeks after enrollment in the OTX-TIC 5 µg arm of the trial, we terminated enrollment in the 5 µg arm of the trial in the fourth quarter of 2022 and continued with the OTX-TIC 26 µg and DURYSTA arms of the trial.

The Phase 2 clinical trial primary study consisted of 83 subjects:

33 subjects in the PAXTRAVA 26 µg treatment arm, 34 subjects in the DURYSTA arm and 16 subjects that were previously enrolled in the PAXTRAVA 5 µg treatment arm.

33 subjects in the OTX-TIC 26 µg treatment arm, 34 subjects in the DURYSTA arm and 16 subjects that were previously enrolled in the OTX-TIC 5 µg treatment arm.

Enrollment of the Phase 2 clinical trial was completed in July 2023.

In April 2024, we presented 6-month topline data from this Phase 2 clinical trial at the 2024 American Society of Cataract and Refractive Surgery Annual Meeting.

In the trial, the PAXTRAVA 26 µg single hydrogel implant demonstrated consistent control of IOP, through six months, as statistically significant IOP changes from baseline were observed for every individual and mean diurnal measurement at primary endpoints Week 2 (M0.5), Week 6 (M1.5), and Week 12 (M3), as well as secondary endpoints Months 4.5 and 6 (p<0.0001), although no formal statistical testing was prespecified by the clinical trial protocol.

In the trial, the OTX-TIC 26 µg single hydrogel implant demonstrated consistent control of IOP, through six months, as statistically significant IOP changes from baseline were observed for every individual and mean diurnal measurement at primary endpoints Week 2 (M0.5), Week 6 (M1.5), and Week 12 (M3), as well as secondary endpoints Months 4.5 and 6 (p<0.0001), although no formal statistical testing was prespecified by the clinical trial protocol.

Clinically meaningful mean IOP reduction of approximately 24-30% from baseline over six months was observed.

A majority (81.3%) of treated eyes did not require additional IOP-lowering therapy through six months, indicating sustained and consistent treatment effects.

PAXTRAVA 26 µg was generally well tolerated with no impact on the corneal endothelium having been observed at six months following a single administration of the product candidate.

OTX-TIC 26 µg was generally well tolerated with no impact on the corneal endothelium having been observed at six months following a single administration of the product candidate.

The majority of adverse events, observed were mild in severity and generally resolved with topical medical treatment.

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Consistent bioresorption of the hydrogel implant coupled with the durable effect observed in the Phase 2 trial suggests redosing could be possible without the risk of implants stacking.

We are conducting a pilot repeat-dose sub-study in the Phase 2 clinical trial to evaluate the safety of a repeat, sustained release dose of PAXTRAVA 26 μg, in a small subset of subjects with OAG or OHT.

These subjects will be followed for at least six months after their enrollment in the sub-study to monitor and evaluate their endothelial cell health.

We completed the pilot repeat-dose sub-study in a subset of subjects from our Phase 2 clinical trial of OTX-TIC to evaluate the safety of a repeat, sustained release dose of OTX-TIC 26 µg.

Subjects in the primary Phase 2 study who had received either OTX-TIC 26 μg or DURYSTA and who did not require rescue therapy during the primary study (prior to Visit 10) were eligible to participate in the repeat dose sub-study.

Subjects who had received OTX-TIC 26 µg in the primary study received a repeat-dose of OTX-TIC 26 μg in the sub-study once the initial dose of OTX-TIC from the

primary study had fully reabsorbed (6 patients at sub-study enrollment;

3 additional patients received sham at sub-study enrollment and OTX-TIC 26 μg at a later study visit following full reabsorption).

As DURYSTA cannot be administered more than once in the same eye, there were 16 subjects who received DURYSTA in the primary study who received sham in their assigned study eye in the repeat-dose sub-study.

Subjects were followed for at least six months after their enrollment in the sub-study and repeat dosing with OTX-TIC 26 µg or sham.

Data from the sub-study were consistent with data previously observed in the OTX-TIC primary study.

We observed a decrease from baseline (Day 0, Visit 2 of the primary study) in mean intraocular pressure, or IOP, values at 8 AM, 10 AM, and 4 PM at all repeat-dose post-injection visits in the study eye in the OTX-TIC 26 µg group and sham group, with mean IOP values similar or lower than those seen at Month 6 of the primary study.

During the repeat-dose sub-study, the mean decrease in diurnal IOP values from baseline was greater at all time points for subjects who received a repeat-dose of OTX-TIC than for subjects who received DURYSTA in the main study and a sham injection in the repeat-dose sub-study.

OTX-TIC 26 µg was generally well tolerated after both single and repeat dosing in patients with OAG or OHT.

In addition, no new safety concerns were identified following repeat-dosing of OTX-TIC 26 µg in the small subset of subjects who participated in the sub-study.

Phase 1 Clinical Development

We submitted an IND for PAXTRAVA in February 2018 and have completed a prospective, multi-center, open-label, dose-escalation, proof-of-concept Phase 1 clinical trial of PAXTRAVA in the United States that we initiated in the second quarter of 2018 for the treatment of subjects with moderate to severe glaucoma or OHT.

The clinical trial is designed to evaluate the safety, biological activity, durability and tolerability of PAXTRAVA in subjects with controlled OAG or OHT.

We submitted an IND for OTX-TIC in February 2018 and have completed a prospective, multi-center, open-label, dose-escalation, proof-of-concept Phase 1 clinical trial of OTX-TIC in the United States that we initiated in the second quarter of 2018 for the treatment of subjects with moderate to severe glaucoma or OHT.

The clinical trial is designed to evaluate the safety, biological activity, durability and tolerability of OTX-TIC in subjects with controlled OAG or OHT.

The clinical trial consisted of four subject cohorts:

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In February 2022, at the Glaucoma 360 virtual meeting, we presented interim results from all four subject cohorts in the Phase 1 clinical trial.

In the Phase 1 clinical trial, at least one subject in each of the four cohorts receiving PAXTRAVA were observed to experience a mean change in IOP from baseline as measured at 8:00 am, 10:00 a.m.

In the Phase 1 clinical trial, at least one subject in each of the four cohorts receiving OTX-TIC were observed to experience a mean change in IOP from baseline as measured at 8:00 am, 10:00 a.m.

and 4:00 p.m.

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IOP lowering effects lasted more than six months in subjects in cohorts 1 and 2 and three to six months in subjects in cohorts 3 and 4.

The PAXTRAVA hydrogel was observed to biodegrade over the course of between five and seven months in subjects in cohorts 1 and 2.

The OTX-TIC hydrogel was observed to biodegrade over the course of between five and seven months in subjects in cohorts 1 and 2.

In subjects in cohorts 3 and 4, the fast-degrading hydrogels were observed to biodegrade over the course of between three and five months.

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IOP elevation was observed in three subjects in cohort 3 at the approximate time of the hydrogel resorption.

Once we have completed the pilot repeat-dose sub-study, we will evaluate whether an end-of-Phase 2 meeting with the FDA is appropriate for determining our next steps for PAXTRAVA for the treatment of OAG or OHT.

Foreign Activities

We have entered into a license agreement and collaboration with AffaMed for the development and commercialization of OTX-TIC for the treatment of OAG or OHT, along with DEXTENZA, in mainland China, Taiwan, Hong Kong, Macau, South Korea, and the countries of the Association of Southeast Asian Nations, or the AffaMed License Agreement.

AffaMed has informed us that they are currently evaluating their next steps for their clinical development program for OTX-TIC.

We are currently evaluating next steps for the OTX-TIC program.

Dry Eye Programs

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The Ocular Therapeutix Approach

Limitations of Current Back-of-the-Eye Injections

The procedure is usually performed by a trained retina specialist in the office setting.

Intravitreal injections are used to administer medications to treat a variety of chronic conditions;

wet AMD, diabetic retinal disease, and RVO are among the most common conditions treated with intravitreal drugs.

The most common intravitreal injections are anti-VEGF drugs.

Anti-VEGF drugs and steroids, which also can be injected intravitreally and are used to treat vascular diseases such as DME and RVO, but not non-vascular diseases such as wet AMD, help to reduce fluid leakage associated with these disorders.

While anti-VEGF treatment regimens can be very effective therapies, there are a number of significant drawbacks, driven primarily by the frequency of injections.

Patients typically require injections every six to eight weeks, but can require them as frequently as every 4 weeks.

We refer to the number of injections a patient has over a given time period as the treatment burden of the particular treatment.

The actual injection at the time of administration is often uncomfortable for patients and can be a deterrent in terms of compliance.

Then there is the burden to both patients and their caregivers of regular office visits.

Most patients require assistance in getting to and from the office visit if they are undergoing injections given the discomfort that can occur post-injection.

In addition, these patients may not be mobile enough to travel to the office on their own and therefore require not only the assistance of a caregiver but also transportation to and from the office.

Patients with diabetic retinal disease are often younger, part of the active workforce and therefore unwilling or unable to take personal time off to receive frequent injections.

Furthermore, frequent injections of medications to the back of the eye can lead to peaks and troughs of medication levels, with fluctuations of intraretinal fluid based on these levels.

Such fluid fluctuations have been associated with decreased vision and possibly fibrosis.

Our Hydrogel-Based Formulation Technology ELUTYX

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We are engaged in the clinical development of our hydrogel administered via intravitreal injection to address the large and growing markets for diseases and conditions of the back of the eye.

Our intravitreal hydrogel product candidates, such as AXPAXLI, consist of a PEG-based hydrogel, which contains embedded micronized particles of active drug.

Our intravitreal hydrogel product candidates, such as AXPAXLI, consist of a PEG-based hydrogel, which contains embedded micronized particles of

We design the intravitreal hydrogel to be injected and retained in the vitreous humor to provide local programmed-release intravitreal delivery of anti-VEGF compounds.

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The hydrogels are designed to be held in place by currents and gravity present in the anterior chamber of an eye.

In the case of PAXTRAVA, the hydrogel is designed to infuse with intracameral water, settle into the inferior angle of the eye and demonstrate little to no movement.

In the case of OTX-TIC, the hydrogel is designed to infuse with intracameral water, settle into the inferior angle of the eye and demonstrate little to no movement.

The hydrogels are soft, biodegradable and provide sustained release of at least one therapeutic agent to both the trabecular meshwork and associated ocular tissue and the fluids within the anterior chamber of an eye.

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In June 2024, we submitted the data for our clinical trial to evaluate DEXTENZA in pediatric subjects following cataract surgery and the updated package insert to the FDA.

We anticipate receiving the FDA’s decision on the pediatric labeling for DEXTENZA during the second quarter of 2025.

We received approval of the supplemental NDA for DEXTENZA in April 2025.

Therefore, DEXTENZA is now also approved for use in pediatric patients for the treatment of ocular inflammation and pain following ophthalmic surgery, and in pediatric patients aged 2 years and older for the treatment of ocular itching associated with allergic conjunctivitis.

The approval of this supplemental NDA provides for pediatric label expansion.

Foreign Approvals

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Given our prioritization of the clinical development of our sustained-release product candidates, in particular for retinal diseases, and our planned commercialization efforts for our initial intracanalicular insert product candidates in the United States, we expect we will need to engage third parties to assist us in the approval process.

We have entered into a license agreement and collaboration with AffaMed for the development and commercialization of DEXTENZA, along with PAXTRAVA in mainland China, Taiwan, Hong Kong, Macau, South Korea, and the countries of the Association of Southeast Asian Nations, or the AffaMed License Agreement .

In January 2022, AffaMed dosed its first subject in a study conducted in China evaluating the safety and efficacy of DEXTENZA for the treatment of ocular inflammation and pain post-cataract surgery.

This prospective, single-arm, real-world trial is designed to assess the safety and efficacy of DEXTENZA for the treatment of ocular inflammation and pain following cataract surgery in approximately 120 subjects at the Bo’ao Super Hospital, or the Bo’ao Real World Study.

The Bo’ao Real World Study’s primary efficacy endpoint is the absence of anterior chamber cells in the study eye at Day 14, and the key secondary endpoint is the absence of pain in the study eye at Day 8.

In October 2023, AffaMed announced positive topline results from the Bo’ao Real World Study .

As announced by AffaMed, the trial met its primary endpoint, with DEXTENZA demonstrating a significant reduction of ocular inflammation as measured by the absence of anterior chamber cells (i.e.

score of "0") in the study eye on Day 14 after cataract surgery.

AffaMed also announced that the trial also met its secondary endpoint, demonstrating a significant reduction of ocular pain on Day 8, and that DEXTENZA was well-tolerated and had a favorable safety profile consistent with all prior trials.

In April 2023, AffaMed announced that China’s National Medical Products Administration, or NMPA, had approved AffaMed’s Clinical Trial Application to initiate a Phase 3 registrational study in China to investigate the efficacy and safety of DEXTENZA in subjects following ophthalmic surgery, or the Phase 3 Registrational Study.

In September 2023, AffaMed announced that the first subject had been treated in the Phase 3 Registrational Study.

In February 2024, AffaMed announced that the Singapore Health Sciences Authority has accepted AffaMed’s new drug application for DEXTENZA for the treatment of ocular inflammation and pain following ophthalmic surgery, and ocular itching associated with allergic conjunctivitis for evaluation.

In April 2022, AffaMed announced that DEXTENZA has been approved in Macau, China for the treatment of ocular inflammation and pain following ophthalmic surgery.

We do not expect that DEXTENZA sales in Macau will result in material revenues to us.

We have entered into the AffaMed License Agreement with AffaMed for the development and commercialization of DEXTENZA, along with OTX-TIC in mainland China, Taiwan, Hong Kong, Macau, South Korea, and the countries of the Association of Southeast Asian Nations.

AffaMed continues to advance its clinical development and regulatory strategy to pursue approval of DEXTENZA for the treatment of ocular inflammation and pain post-ophthalmic surgery by China’s National Medical Products Administration, or NMPA.

AffaMed has obtained approval to market DEXTENZA for the treatment of ocular inflammation and pain post-ophthalmic surgery in Macau and Singapore.

We do not expect that DEXTENZA sales in Macau and Singapore will result in material revenues to us.

We retain the right to develop and commercialize DEXTENZA in all other global markets.

From time to time, we may consider additional arrangements with other companies to address markets outside of the United States.

If we or our collaborators obtain regulatory approval to market and sell DEXTENZA in international markets, we expect to utilize a variety of types of collaboration, distribution and other marketing arrangements with one or more third parties to commercialize DEXTENZA.

See “—Government Regulation—Review and Approval of Medical Devices in the European Union” for additional information.

Allergic Conjunctivitis

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With the approval, DEXTENZA became the first, FDA-approved, physician-administered intracanalicular insert capable of delivering a preservative-free drug for the treatment of ocular itching associated with allergic conjunctivitis with a single administration for up to 30 days.

DEXTENZA for the treatment of ocular itching associated with allergic conjunctivitis also represents our first indication approved to be administered in a physician’s office during a routine, non-surgical appointment.

DEXTENZA for the treatment of ocular itching associated with allergic conjunctivitis

also represents our first indication approved to be administered in a physician’s office during a routine, non-surgical appointment.

We commercially launched DEXTENZA for the treatment of ocular itching associated with allergic conjunctivitis in the first quarter of 2022.

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In the fourth quarter of 2021, we received a $1.0 million milestone payment upon the approval by the FDA of an sNDA for DEXTENZA to include the treatment of ocular itching associat ed with allergic conjunctivitis as an additional indication ;

in the second quarter of 2022, we received a $2 million clinical support payment in connection with dosing the first subject in a Phase 2 clinical trial evaluating PAXTRAVA for the treatment of OAG or OHT;

and in the second quarter of 2023, we received a $1 million milestone payment upon the NMPA’s approval of AffaMed’s Phase 3 Registrational Study.

in the second quarter of 2022, we received a $2.0 million clinical support payment in connection with dosing the first subject in a Phase 2 clinical trial evaluating OTX-TIC for the treatment of OAG or OHT;

and in the second quarter of 2023, we received a $1.0 million milestone payment upon the NMPA’s approval of AffaMed’s Phase 3 registrational study in China to investigate the efficacy and safety of DEXTENZA in subjects following ophthalmic surgery.

Royalties are tiered and will range from the low teens to low twenty percent range.

In return, we agreed to grant AffaMed exclusive rights to develop and commercialize DEXTENZA for the treatment of post-surgical inflammation and pain following ophthalmic surgery and ocular itching in patients with allergic conjunctivitis, and PAXTRAVA for the reduction of elevated IOP in patients with primary OAG or OHT in specified Asian markets.

We retain the right to develop and commercialize DEXTENZA and PAXTRAVA in all other global markets.

In return, we agreed to grant AffaMed exclusive rights to develop and commercialize DEXTENZA for the treatment of post-surgical inflammation and pain following ophthalmic surgery and ocular itching in patients with allergic conjunctivitis, and OTX-TIC for the reduction of elevated IOP in patients with primary OAG or OHT in specified Asian markets.

We retain the right to develop and commercialize DEXTENZA and OTX-TIC in all other global markets.

Sales, Marketing and Distribution

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If we decide to commercialize our products outside of the United States, we expect to utilize a variety of types of collaboration, distribution and other marketing arrangements with one or more third parties to commercialize any product of ours that receives marketing approval.

We sell DEXTENZA in the United States to specialty distributors, or SDs, for resale to certain ambulatory surgery centers, or ASCs, certain hospital outpatient departments, or HOPDs, and certain physicians’ offices, and directly to

certain ASCs and physicians’ offices.

We are continuing to offer this distribution option more broadly to our end customers.

In addition to distribution agreements with specialty distributors and a small number of ASCs and physicians’ offices, we enter into arrangements with government payors that provide for government-mandated rebates and chargebacks with respect to the purchase of DEXTENZA.

We have built a highly targeted, key account sales force of KAMs, or key account managers, Regional Directors, and FRMs, or field reimbursement managers, that focus on the ASCs and their affiliates responsible for the largest volumes of cataract surgery in the United States, with an initial emphasis on the approximately two million cataract procedures performed annually under Medicare Part B.

We have built a highly targeted, key account sales force of KAMs, or key account managers, Regional Directors, and FRMs, or field reimbursement managers, that primarily focuses on the ASCs and their affiliates, as well as HOPDs, that were, according to the MarketScope Ophthalmic Market Trends:

Quarterly US Cataract Edition (published November 2025) Report, collectively responsible for approximately 86.9% of the approximately 4.8 million cataract procedures that were performed in the United States in 2024.

Since 2022, we have periodically adjusted our discounting and rebate strategy to meet the demands of the market.

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Manufacturing

We fabricate devices and drug products for use in our clinical trials, research and development and commercial efforts for DEXTENZA using current Good Manufacturing Practices, or cGMP, at our approximately 20,000 square foot facility located in Bedford, Massachusetts.

We fabricate devices and drug products for use in our clinical trials and other research and development activities for our product candidates, including AXPAXLI, using cGMP at our 71,000 square foot facility that is also located in Bedford, Massachusetts.

This facility may include additional manufacturing space in the future as we increase our manufacturing capacity and capabilities for AXPAXLI.

We fabricate devices and drug products for use in our clinical trials, research and development and commercial efforts for DEXTENZA according to current good manufacturing practices, or cGMP, at our approximately 20,000 square foot facility located in Bedford, Massachusetts.

We fabricate drug products and assemble the final products for use in our clinical trials and other research and development activities for our product candidates, including AXPAXLI, at our 71,000 square foot cGMP facility that is also located in Bedford, Massachusetts.

We are completing additional construction at this facility to support initial expected commercial demand for AXPAXLI.

We purchase active pharmaceutical ingredient drug substance from independent suppliers on a purchase order basis for incorporation into our drug product candidates.

We purchase our PEG and other raw materials from different vendors on a purchase order basis according to our specifications.

We purchase components for our injectors and for the manufacture of our hydrogel platform from several different vendors.

While we believe that multiple vendors are available for each component we purchase, we have historically sole-sourced each component.

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We do not license any technology or pay any royalties to any of our drug or raw material vendors for the current or potential front and back-of-the-eye products.

We believe that our strategic investment in manufacturing capabilities allows us to advance product candidates at a more rapid pace and with more flexibility than if we were to work with a contract manufacturer, although we will continue to evaluate outsourcing unit operations for cost advantages or eventually as a second source.

We believe that our strategic investment in manufacturing capabilities allows us to advance product candidates at a more rapid pace, with more flexibility and greater level of quality, than if we were to work with a contract manufacturer.

We will continue to evaluate outsourcing unit operations for cost advantages or eventually as a second source.

Our manufacturing capability also enables us to produce products in a cost-effective manner while retaining control over the manufacturing process and prioritizing the timing of internal programs.

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We outsource sterilization and packaging services for our products.

We believe that we can scale our manufacturing processes to support DEXTENZA sales as well as development of our drug product candidates and the potential commercialization of such product candidates, including AXPAXLI.

We believe that we can continue to execute our commercial manufacturing to support DEXTENZA sales, to supply clinical materials for our current and future development programs for AXPAXLI and other product candidates, and to scale up our manufacturing processes for the potential commercialization of AXPAXLI.

Intellectual Property

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The term of individual patents depends upon the legal term for patents in the countries in which they are granted.

In most countries, including the United States, the patent term is generally 20 years from the earliest claimed filing date of a non-provisional patent application in the applicable country.

In most countries, including the United States, the patent term is generally 20 years from the earliest claimed filing date of a patent application in the applicable country (not including provisional filings in the United States).

In the United States, a patent’s term may, in certain cases, be lengthened by patent term adjustment, which compensates a patentee for administrative delays by the United States Patent and Trademark Office in examining and granting a patent, or may be shortened if a patent is terminally disclaimed over a commonly owned patent or a patent naming a common inventor and having an earlier expiration date.

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A patent term extension cannot extend the remaining term of a patent beyond a total of 14 years from the date of product approval, only one patent applicable to each regulatory review period may be extended and only those claims covering the approved drug, a method for using it or a method for manufacturing it may be extended.

Patent term extension is only available for the first commercial marketing or use of the product under the provision of law under which the regulatory review period occurred.

Similar provisions are available in the European Union and certain other foreign jurisdictions to extend the term of a patent that covers an approved drug.

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AXPAXLI (axitinib intravitreal hydrogel)

We own issued patents in the United States and patents in certain foreign jurisdictions that cover this product candidate, with current expiration dates in 2041.

We own a pending Patent Cooperation Treaty application with the potential to cover this product candidate in the U.S.

and foreign jurisdictions, that, if granted, is expected to expire in 2044.

Additional U.S.

and foreign patent applications are pending.

PAXTRAVA (travoprost intracameral hydrogel) for the treatment of OAG or OHT

We own an issued patent in the United States that covers this product candidate, with a current expiration date in 2044 as well as corresponding pending U.S.

and foreign counterpart applications, together with other issued patents in the United States and patents in certain foreign jurisdictions that cover this product candidate, with current expiration dates in 2041, as well as corresponding pending U.S.

and foreign counterpart applications.

OTX-TIC (travoprost intracameral hydrogel) for the treatment of OAG or OHT

We have licenses to a U.S.

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and foreign counterparts.

We own an issued patent in the United States and patents in certain foreign jurisdictions that cover this product candidate, with current expiration dates in 2041.

Additional owned U.S.

and foreign patent applications are pending.

We own an issued patent in the United States and patents in certain foreign jurisdictions that cover this product candidate, with current expiration dates in 2041 as well as corresponding pending U.S.

and foreign counterpart applications.

DEXTENZA (dexamethasone ophthalmic insert) 0.4 mg

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We also own an issued U.S.

patent expiring in 2041, and related pending U.S.

and foreign applications.

patent expiring in 2041, as well as corresponding pending U.S.

and foreign counterpart applications.

In January 2012, we entered into an amended and restated license agreement, which we refer to as either the Prior Agreement or Original License, with Incept under which we hold an exclusive, worldwide, perpetual, irrevocable license under specified patents and technology owned or controlled by Incept to make, have made, use, offer for sale, sell, sublicense, have sublicensed, offer for sublicense and import, products delivered to or around the human eye for diagnostic, therapeutic or prophylactic purposes relating to all human ophthalmic diseases or conditions.

This license covers a significant portion of the patent rights and the technology for DEXTENZA, ReSure Sealant and our hydrogel platform technology product candidates.

This license covers a significant portion of the patent rights and the technology for DEXTENZA, and may cover certain aspects of other hydrogel platform technology product candidates, such as OTX-TIC, to the extent they were invented prior to the Effective Date (referred to below).

The agreement supersedes an April 2007 license agreement between us and Incept.

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(i) consistent with the Prior Agreement, a royalty equal to a low single-digit percentage of net sales by us or our affiliates of products, devices, materials, or components thereof, or Licensed Products, including or covered by Original IP, excluding the Shape-Changing IP, in the Ophthalmic Field of Use;

(ii) a royalty equal to a mid-

single-digit percentage of net sales by us or our affiliates of Licensed Products including or covered by Original IP, excluding the Shape-Changing IP, in the Additional Field of Use;

(ii) a royalty equal to a mid-single-digit percentage of net sales by us or our affiliates of Licensed Products including or covered by Original IP, excluding the Shape-Changing IP, in the Additional Field of Use;

and (iii) a royalty equal to a low single-digit percentage of net sales by us or our affiliates of Licensed Products including or covered by Incept IP or Joint IP in the field of drug delivery.

Royalty obligations under the Second Amended Agreement commence with the first commercial sale of a Licensed Product described above and terminate upon the expiration of the last-to-expire patents included in the Licensed IP, as applicable.

Royalty obligations under the Second Amended Agreement commence with the first commercial

sale of a Licensed Product described above and terminate upon the expiration of the last-to-expire patents included in the Licensed IP, as applicable.

Any sublicensee of us also will be obligated to pay Incept royalties on net sales of Licensed Products made by it and will be bound by the terms of the Second Amended Agreement to the same extent as us.

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AffaMed License Agreement

On October 29, 2020, we entered into the AffaMed License Agreement with AffaMed for the development and commercialization of DEXTENZA regarding ocular inflammation and pain following cataract surgery and allergic conjunctivitis, or collectively, the DEXTENZA Field, and for PAXTRAVA, or collectively with DEXTENZA, the AffaMed Licensed Products, regarding OAG and OHT, or collectively, the TIC Field and, with the DEXTENZA Field, each a Field, in each case in mainland China, Taiwan, Hong Kong, Macau, South Korea, and the countries of the Association of Southeast Asian Nations, or collectively, the Territories.

On October 29, 2020, we entered into the AffaMed License Agreement with AffaMed for the development and commercialization of DEXTENZA regarding ocular inflammation and pain following cataract surgery and allergic conjunctivitis, or collectively, the DEXTENZA Field, and for OTX-TIC, or collectively with DEXTENZA, the AffaMed Licensed Products, regarding OAG and OHT, or collectively, the TIC Field and, with the DEXTENZA Field, each a Field, in each case in mainland China, Taiwan, Hong Kong, Macau, South Korea, and the countries of the Association of Southeast Asian Nations, or collectively, the Territories.

We retain development and commercialization rights for the AffaMed Licensed Products in the rest of the world.

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There can be no guarantee, however, that any of the remaining milestones will be achieved.

We are also entitled to receive tiered,

escalating royalties on the net sales of the AffaMed Licensed Products ranging from a low-teen to low-twenties percentage.

We are also entitled to receive tiered, escalating royalties on the net sales of the AffaMed Licensed Products ranging from a low-teen to low-twenties percentage.

Royalties under the AffaMed License Agreement are payable on an AffaMed Licensed Product-by-AffaMed Licensed Product and jurisdiction-by-jurisdiction basis and are subject to potential reductions in specified circumstances, subject to a specified floor.

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During an established period following a change of control of us or our entry into a global licensing agreement that includes the Territories with a third party, we have the option to terminate the AffaMed License Agreement, subject to a specified notice period and the repayment of any costs and expenses incurred by AffaMed in connection with the AffaMed License Agreement, including upfront and milestone payments AffaMed has previously paid to us, at a prespecified premium.

AffaMed has the right to terminate the AffaMed License Agreement at any time following the completion of a Phase 3 clinical trial to evaluate PAXTRAVA.

AffaMed has the right to terminate the AffaMed License Agreement at any time following the completion of a Phase 3 clinical trial to evaluate OTX-TIC.

The biotechnology and pharmaceutical industries are characterized by rapidly advancing technologies, intense competition and a strong emphasis on proprietary products.

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The key competitive factors affecting the success of each of our product candidates, if approved for marketing, are likely to be efficacy, safety, method and frequency of administration, convenience, price, the level of generic competition and the availability of coverage and adequate reimbursement from government and other third-party payors.

Because the active pharmaceutical ingredients in our product candidates are available on a generic basis, or are soon to be available on a generic basis, competitors will be able to offer and sell products with the same active

pharmaceutical ingredient as our products so long as these competitors do not infringe the patents that we license.

For example, our licensed patents related to our intracanalicular insert product candidates largely relate to the hydrogel composition of the intracanalicular inserts and certain drug-release features of the intracanalicular inserts.

As such, if a third party were able to design around the formulation and process patents that we license and create a different formulation using a different production process not covered by our licensed patents or patent applications, we would likely be unable to prevent that third party from manufacturing and marketing its product.

Because the active pharmaceutical ingredients in our products and product candidates are available off-patent, or are soon to be available off-patent, competitors will be able to offer and sell products with the same active pharmaceutical ingredient as our products so long as these competitors do not infringe the patents that we own or license.

For example, certain of our owned and licensed patents cover the composition of our products and product candidates and associated methods that relate to the hydrogel composition and drug-release features of the products and product candidates.

As such, if a third party were able to design around the formulation and method patents that we own or license and create a different formulation using a different production process not covered by our owned or licensed

patents or patent applications, we would likely be unable to prevent that third party from manufacturing and marketing its product.

Competitors to AXPAXLI

In wet AMD and DR, AXPAXLI will compete with anti-VEGF compounds administered in their current formulation and prescribed for the treatment of wet AMD as these agents can in some instances deliver more than one or two months of therapeutic effect.

They include Lucentis (ranibizumab), Eylea (aflibercept 2 mg), Eylea HD (aflibercept 8 mg), Beovu (brolicizumab), Vabysmo (faricimab), Susvimo (ranibizumab Port Delivery System), and off-label use of the cancer therapy Avastin.

Biosimilars to ranibizumab and aflibercept 2 mg have received FDA approval as well.

In wet AMD and diabetic retinal disease, AXPAXLI will compete with anti-VEGF compounds administered in their current formulation and prescribed for the treatment of wet AMD as these agents can in some instances deliver more than one or two months of therapeutic effect, as well as products based on gene therapy, if such products are approved.

Anti-VEGF products that are currently approved by the FDA for the treatment of wet AMD include Vabysmo (faricimab), Eylea HD (aflibercept 8 mg), Lucentis (ranibizumab), Eylea (aflibercept 2 mg), Beovu (brolicizumab), and Susvimo (ranibizumab Port Delivery System).

Biosimilars to ranibizumab and aflibercept 2 mg are commercially available as well.

Products that are currently approved by the FDA for the treatment of various diabetic retinal disease indications include Vabysmo, Eylea HD, Lucentis, Eylea, Beovu and Susvimo.

The FDA-approved labels for Vabysmo and Eylea HD contemplate dosing as infrequently as once every 16 weeks for a proportion of patients for wet AMD and diabetic retinal disease.

The cancer therapy Avastin (bevacizumab) is used off-label for the treatment of wet AMD and diabetic retinal disease as well.

These treatments are only sparingly used for the treatment of non-proliferative diabetic retinopathy, though, largely due to the treatment burden.

Multiple companies, in various stages of development, are pursuing products for wet AMD that would be competitive with AXPAXLI.

Programs in later-stage development include:

Eyepoint Pharmaceuticals, which is pursuing a sustained-release bioerodible device containing a TKI (vorolanib) using its Durasert-E technology;

Opthea, which is pursuing an anti-VEGF C/D Trap evaluated in combination with anti-VEGF;

Clearside Biomedical, which is pursuing a TKI (axitinib) administered into the suprachoroidal space;

and Kodiak Sciences, which is pursuing products based on its anti-VEGF biopolymer conjugate technology.

In addition, there are several companies pursuing gene therapies to treat wet AMD including, 4D Molecular Therapeutics, Adverum Biotechnologies and RegenxBio.

Eyepoint Pharmaceuticals, which is pursuing a sustained-release bioerodible implant containing a TKI (vorolanib) using its Durasert-E technology and Kodiak Sciences, which is pursuing products based on its antibody biopolymer conjugate technology.

In addition, there are several companies pursuing gene therapies to treat wet AMD including, 4D Molecular Therapeutics, Adverum Biotechnologies, which was acquired by Eli Lilly and Company in 2025, and RegenxBio.

Programs in early phases of development include but are not limited to:

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and Roche, which is pursuing intravitreal products along with those delivered with its Port Delivery System technology.

In DR, AXPAXLI will compete with approved agents, including Lucentis, Eylea and Eylea HD.

These treatments, although approved for DR, are sparingly used, largely due to the treatment burden.

Multiple companies, in various stages of development, are pursuing products that would be competitive with AXPAXLI.

Multiple companies, in various stages of development, are pursuing products for the treatment of diabetic retinal disease that would be competitive with AXPAXLI.

Programs in later-stage development include:

Roche, which is pursuing Susvimo for the treatment of DR;

Kodiak Sciences, which is pursuing an anti-VEGF molecule built on its antibody polymer conjugate technology;

RegenxBio, which is pursuing a suprachoroidal formulation of its gene therapy for the treatment of DR;

and Opus Genetics, which is pursuing an oral treatment.

Competitors to PAXTRAVA

Merck, which is pursuing a wingless-related integration site (Wnt) agonist for the treatment of DME;

Opus Genetics;

which is pursuing an oral treatment;

and Eyepoint, which is pursuing a sustained-release bioerodible implant containing a TKI (vorolanib) using its Durasert-E technology for the treatment of DME.

Competitors to OTX-TIC

A number of therapies are currently available for the treatment of glaucoma in the United States.

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received FDA approval of DEXYCU in February 2018.

DEXYCU is an injection of dexamethasone at the time of surgery into the posterior chamber of the eye (behind the iris) to treat inflammation associated with cataract surgery.

DEXYCU is an injection of dexamethasone at the time of surgery into the posterior chamber of the eye (behind the iris) to treat inflammation

associated with cataract surgery.

Icon Biosciences Inc.

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DEXYCU lost separate government reimbursement as of January 1, 2023 and is no longer actively marketed.

OMIDRIA, purchased by Rayner Surgical Group Limited, is a prescription medication used during cataract

OMIDRIA, purchased by Rayner Surgical Group Limited, is a prescription medication used during cataract surgery.

According to the OMIDRIA website, this product helps the black part in the center of the eye (pupil) stay open (dilated) during cataract surgery and decreases eye pain after surgery.

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While animal testing may still be conducted, the FDA was authorized to rely on alternative non-clinical tests, including cell-based assays, microphysiological systems, or bioprinted or computer models.

In April 2025, the FDA released a roadmap to replace animal testing in preclinical safety studies with scientifically validated new approach methodologies, such as organ-on-a-chip systems and computational modeling, which are referred to as in silico models, as well as advanced in vitro assays.

The IND and IRB Processes

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This waiting period is designed to allow the FDA to review the IND to assure the safety and rights of patients and to help assure that the quality of the investigation will be adequate to permit an evaluation of the drug’s effectiveness and safety and of the biological product’s safety, purity and potency .

At any time during this 30-day period, or thereafter, the FDA may raise concerns or questions about the conduct of the trials as outlined in the IND and impose a clinical hold or partial clinical hold.

At any time during this 30-day period, or thereafter, the FDA

may raise concerns or questions about the conduct of the trials as outlined in the IND and impose a clinical hold or partial clinical hold.

In this case, the IND sponsor and the FDA must resolve any outstanding concerns before clinical trials can begin.

In addition to the foregoing IND requirements, an IRB representing each institution participating in the clinical trial must review and approve the plan for any clinical trial before it commences at that institution, and the IRB must conduct continuing review and reapprove the study at least annually.

The IRB must review and approve, among other

things, the study protocol and informed consent information to be provided to study subjects.

The IRB must review and approve, among other things, the study protocol and informed consent information to be provided to study subjects.

An IRB must operate in compliance with FDA regulations.

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The responsible party, however, is allowed 30 days to correct the noncompliance and submit the required information.

As of December 19, 2024, the FDA has issued six notices of non-compliance, thereby signaling the government’s willingness to begin enforcing these requirements against non-compliant clinical trial sponsors.

As of December 19, 2025, the FDA has issued eight notices of non-compliance, thereby signaling the government’s willingness to begin enforcing these requirements against non-compliant clinical trial sponsors.

While these notices of non-compliance did not result in civil monetary penalties, the failure to submit clinical trial information to clinicaltrials.gov is a prohibited act under the FDCA with violations subject to potential civil monetary penalties of up to $10,000 for each day the violation continues.

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patient(s) have a serious or immediately life-threatening disease or condition, and there is no comparable or satisfactory alternative therapy to diagnose, monitor, or treat the disease or condition;

the potential patient benefit justifies the potential risks of the treatment and the potential risks are not unreasonable in the context or condition to be treated;

potential patient benefit justifies the potential risks of the treatment and the potential risks are not unreasonable in the context or condition to be treated;

and the expanded use of the investigational drug for the requested treatment will not interfere initiation, conduct, or completion of clinical investigations that could support marketing approval of the product or otherwise compromise the potential development of the product.

There is no obligation for a sponsor to make its investigational products available for expanded access;

however, as required by amendments to the FDCA included in the 21st Century Cures Act, or the Cures Act, passed in 2016, if a

sponsor has a policy regarding how it responds to expanded access requests with respect to product candidates in development to treat serious diseases or conditions, it must make that policy publicly available.

however, as required by amendments to the FDCA included in the 21st Century Cures Act, or the Cures Act, passed in 2016, if a sponsor has a policy regarding how it responds to expanded access requests with respect to product candidates in development to treat serious diseases or conditions, it must make that policy publicly available.

Sponsors are required to make such policies publicly available upon the earlier of initiation of a Phase 2 or Phase 3 study for a covered investigational product;

or 15 days after the investigational product receives designation from the FDA as a breakthrough therapy, fast track product, or regenerative medicine advanced therapy.

In October 2025, the FDA issued final guidance further clarifying the statutory and regulatory requirements governing expanded access.

In addition, on May 30, 2018, the Right to Try Act was signed into law.

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A clinical trial may combine the elements of more than one phase, and the FDA often requires more than one Phase 3 trial to support marketing approval of a product candidate.

A company’s designation of a clinical trial as being of a particular phase is not necessarily indicative that the study will be sufficient to satisfy the FDA requirements of that phase because this determination cannot be made until the protocol and data have been submitted to and reviewed by the FDA.

A company’s designation of a clinical trial as being of a particular phase is not necessarily indicative that the study will be sufficient to satisfy the FDA requirements of that

phase because this determination cannot be made until the protocol and data have been submitted to and reviewed by the FDA.

Moreover, as noted above, a pivotal trial is a clinical trial that is believed to satisfy FDA requirements for the evaluation of a product candidate’s safety and efficacy such that it can be used, alone or with other pivotal or non-pivotal trials, to support regulatory approval.

Generally, pivotal trials are Phase 3 trials, but they may be Phase 2 trials if the design provides a well-controlled and reliable assessment of clinical benefit, particularly in an area of unmet medical need.

In December 2022, with the passage of Food and Drug Omnibus Reform Act, or FDORA, Congress began requiring sponsors to develop and submit a diversity action plan, or DAP, for each Phase 3 clinical trial or any other “pivotal study” of a new drug or biological product.

In December 2022, with the passage of Food and Drug Omnibus Reform Act, or FDORA, Congress required sponsors to develop and submit a diversity action plan, or DAP, for each Phase 3 clinical trial or any other “pivotal study” of a new drug or biological product.

These plans are meant to encourage the enrollment of more diverse patient populations in late-stage clinical trials of FDA-regulated products.

Specifically, DAPs must include the sponsor’s goals for enrollment, the underlying rationale for those goals, and an explanation of how the sponsor intends to meet them.

In addition to these requirements, the legislation directs the FDA to issue new guidance on DAPs.

In June 2024, as mandated by FDORA, the FDA issued draft guidance outlining the general requirements for DAPs.

Unlike most guidance documents issued by the FDA, the DAP guidance when finalized will have the force of law because FDORA specifically dictates that the form and manner for submission of DAPs are specified in FDA guidance.

On January 27, 2025, in response to an Executive Order issued by President Trump on January 21, 2025, on Diversity, Equity and Inclusion programs, the FDA removed this draft guidance from its website.

This action raises questions about the applicability of statutory obligations to submit DAPs and the agency’s current thinking on best practices for clinical development.

In June 2023, the FDA issued draft guidance with updated recommendations for GCPs aimed at modernizing the design and conduct of clinical trials.

On January 27, 2025, in response to an executive order issued by President Trump on January 21, 2025, relating to Diversity, Equity and Inclusion programs, the FDA removed the draft DAP guidance from its website.

That action, along with similar actions by the Trump Administration to remove many other healthcare webpages, is currently the subject of ongoing litigation.

On July 3, 2025, the U.S.

District Court for the District of Columbia ruled that the Trump Administration’s actions to remove these webpages, including the draft DAP guidance, are unlawful under the Administrative Procedure Act.

The court ordered the restoration of many of these webpages.

In late July 2025, the FDA restored the draft DAP guidance to its website with a statement that “information on this page may be modified and/or removed in the future subject to the terms of the court’s order and implemented consistent with applicable law.” Accordingly, in light of these ongoing actions, there is considerable uncertainty surrounding the draft DAP guidance and how the FDA will consider DAPs in connection with its review of NDAs and BLAs.

In September 2025, the FDA issued final guidance with updated recommendations for GCPs aimed at modernizing the design and conduct of clinical trials.

The updates are intended to help pave the way for more efficient clinical trials to facilitate the development of medical products.

The draft guidance is adopted from the International Council for Harmonisation’s recently updated E6(R3) draft guideline that was developed to enable the incorporation of rapidly developing technological and methodological innovations into the clinical trial enterprise.

In addition, the FDA issued draft guidance outlining recommendations for the implementation of decentralized clinical trials.

The final guidance is adopted from the International Council for Harmonisation’s recently updated E6(R3) final guideline that was developed to enable the incorporation of rapidly developing technological and methodological innovations into the clinical trial enterprise.

In September 2024, the FDA finalized guidance outlining recommendations for the implementation of decentralized clinical trials.

Clinical Trials Outside the United States in Support of FDA Approval

In connection with our clinical development program, we have trial sites outside the United States from time to time.

In connection with our clinical development program, we utilize trial sites outside the United States from time to time.

When a foreign clinical trial is conducted under an IND, all IND requirements must be met unless waived.

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and (iii) the data may be considered valid without the need for an on-site inspection by the FDA, or if the FDA considers such inspection to be necessary, the FDA is able to validate the data through an on-site inspection or other appropriate means.

In addition, even where the foreign trial data are not intended to serve as the sole basis for approval, the FDA will not accept the data as support for an application for marketing approval unless the trial is well-designed and well-conducted in accordance with GCP requirements and the FDA is able to validate the data from the trial through an onsite inspection if deemed necessary.

In December 2025, in the context of negotiations involving reauthorization of Prescription Drug User Fee Act, or PDUFA, the FDA proposed cutting fees for companies conducting clinical development programs in the United States, rather than abroad.

It is unclear whether and how this proposal will be adopted and finalized.

conducted in accordance with GCP requirements and the FDA is able to validate the data from the trial through an onsite inspection if deemed necessary.

Many foreign regulatory authorities have similar approval requirements.

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findings from other studies or animal or in vitro testing that suggest a significant risk in humans exposed to the product candidate;

and any clinically important increase in the occurrence of a serious suspected

adverse reaction over that listed in the protocol or investigator brochure.

and any clinically important increase in the occurrence of a serious suspected adverse reaction over that listed in the protocol or investigator brochure.

Phase 1, Phase 2 and Phase 3 clinical trials may not be completed successfully within any specified period, or at all.

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animal carcinogenicity protocols, final product stability protocols and clinical protocols for Phase 3 trials where the data will form the primary basis for an efficacy claim.

The FDA may meet with sponsors, provided certain conditions are met, for the purpose of reaching an SPA agreement on the design and size of clinical trials intended to form the primary basis of an efficacy claim in a marketing application.

The FDA may meet with sponsors, provided certain conditions are met, for the purpose of reaching a SPA agreement on the design and size of clinical trials intended to form the primary basis of an efficacy claim in a marketing application.

If a sponsor makes a reasonable written request to meet with the FDA for the purpose of reaching agreement on the design and size of a clinical trial, then the FDA will meet with the sponsor.

If an agreement is reached, the FDA will reduce the agreement to writing and make it part of the administrative record.

An agreement may not be changed by the sponsor or FDA after the trial begins, except with the written agreement of the sponsor and FDA, or if the director of the FDA reviewing division determines that “a substantial scientific issue essential to determining the safety or effectiveness of the investigational product was identified after the testing began.

effectiveness of the investigational product was identified after the testing began.

If a sponsor and the FDA meet regarding the design and size of a clinical trial and the parties cannot agree that the trial design is adequate to meet the goals of the sponsor, the FDA will clearly state the reasons for the disagreement in a letter to the sponsor.

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Concurrently with clinical trials, sponsors usually complete additional animal safety studies, develop additional information about the chemistry and physical characteristics of the product candidate and finalize a process for manufacturing commercial quantities of the product candidate in accordance with cGMP requirements.

The manufacturing process must be capable of consistently producing quality batches of the product candidate and, among other criteria, the sponsor must develop methods for testing the identity, strength, quality, and purity of the finished

Additionally, appropriate packaging must be selected and tested and stability studies must be conducted to demonstrate that the product candidate does not undergo unacceptable deterioration over its shelf life.

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The PREVENT Pandemics Act, which was enacted in December 2022, clarifies that foreign drug manufacturing establishments are subject to registration and listing requirements even if a drug or biologic undergoes further manufacture, preparation, propagation, compounding, or processing at a separate establishment outside the United States prior to being imported or offered for import into the United States.

In May 2025, the FDA disclosed plans to expand its use of unannounced inspections of foreign manufacturing facilities that produce drugs and biologics distributed in the United States.

Pediatric Studies

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A deferral may be granted for several reasons, including a finding that the product or therapeutic candidate is ready for approval for use in adults before pediatric trials are complete or that additional safety or effectiveness data needs to be collected before the pediatric trials begin.

Pursuant to the Food and Drug Administration Safety and Innovation Act of 2012, or FDASIA, the FDA must send a PREA Non-Compliance letter to sponsors who have failed to submit their pediatric assessments required under PREA, have failed to seek or obtain a deferral or deferral extension or have failed to request approval for a required pediatric formulation.

Pursuant to the Food and Drug Administration Safety and Innovation Act of 2012, or FDASIA, the FDA must send a PREA Non-Compliance letter to sponsors who have failed to

submit their pediatric assessments required under PREA, have failed to seek or obtain a deferral or deferral extension or have failed to request approval for a required pediatric formulation.

It further requires the FDA to publicly post the PREA Non-Compliance letter and sponsor’s response.

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To support marketing approval, the data submitted must be sufficient in quality and quantity to establish the safety and efficacy of a drug product and the safety, potency and purity of the biological product to the satisfaction of the FDA.

The fee required for the submission and review of an application under the Prescription Drug User Fee Act, or PDUFA, is substantial (for example, for FY2025 this application fee is approximately $4.3 million), and the sponsor of an approved application is also subject to an annual program fee, which for FY2025 is currently set at $403,889 per eligible prescription product.

The fee required for the submission and review of an application under PDUFA is substantial (for example, for FY2026 this application fee is approximately $4.7 million), and the sponsor of an approved application is also subject to an annual program fee, which for FY2026 is currently set at $442,213 per eligible prescription product.

These fees are typically adjusted annually, and exemptions and waivers may be available under certain circumstances, such as where a waiver is necessary to protect the public health, where the fee would present a significant barrier to innovation, or where the sponsor is a small business submitting its first human therapeutic application for review.

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Typically, an RTF will be based on administrative incompleteness, such as clear omission of information or sections of required information;

scientific incompleteness, such as omission of critical data, information or analyses needed to evaluate safety and efficacy or provide adequate directions for use;

scientific incompleteness,

such as omission of critical data, information or analyses needed to evaluate safety and efficacy or provide adequate directions for use;

or inadequate content, presentation, or organization of information such that substantive and meaningful review is precluded.

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After the submission is accepted for filing, the FDA begins an in-depth substantive review of the application.

The FDA reviews the application to determine, among other things, whether the proposed product is safe and effective for its intended use, whether it has an acceptable purity profile and whether the product is being manufactured in accordance

Under the goals and policies agreed to by the FDA under PDUFA, the FDA has ten months from the filing date in which to complete its initial review of a standard application that is a new molecular entity, and six months from the filing date for an application with “priority review.” The review process may be extended by the FDA for three additional months to consider new information or in the case of a clarification provided by the sponsor to address an outstanding deficiency identified by the FDA following the original submission.

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The FDA determines the requirement for a REMS, as well as the specific REMS provisions, on a case-by-case basis.

If the FDA concludes a REMS is needed, the sponsor of the application must submit a proposed REMS and the FDA will not approve the application without a REMS.

concludes a REMS is needed, the sponsor of the application must submit a proposed REMS and the FDA will not approve the application without a REMS.

Decisions on NDAs and BLAs

The FDA reviews a sponsor to determine, among other things, whether the product is safe and whether it is effective for its intended use(s), with the latter determination being made on the basis of substantial evidence.

effectiveness of the product involved, on the basis of which it could fairly and responsibly be concluded by such experts that the product will have the effect it purports or is represented to have under the conditions of use prescribed, recommended, or suggested in the labeling or proposed labeling thereof.”

The FDA reviews an application to determine, among other things, whether the product is safe and whether it is effective for its intended use(s), with the latter determination being made on the basis of substantial evidence.

The term “substantial evidence” is defined under the FDCA as “evidence consisting of adequate and well-controlled investigations, including clinical investigations, by experts qualified by scientific training and experience to evaluate the effectiveness of the product involved, on the basis of which it could fairly and responsibly be concluded by such experts that the product will have the effect it purports or is represented to have under the conditions of use prescribed, recommended, or suggested in the labeling or proposed labeling thereof.”

The FDA has interpreted this evidentiary standard to require at least two adequate and well-controlled clinical investigations to establish effectiveness of a new product.

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The FDA also issued draft guidance in September 2023 that outlines considerations for relying on confirmatory evidence in lieu of a second clinical trial to demonstrate efficacy.

The FDA has not yet finalized such guidance.

The FDA has not yet finalized such guidance, but, in December 2025, and again in January 2026, the FDA signaled that it is considering only requiring one clinical trial for approval of most drug products.

The FDA indicated in December 2025 that it may issue guidance regarding this change through a press release or other means.

After evaluating the application and all related information, including the advisory committee recommendations, if any, and inspection reports of manufacturing facilities and clinical trial sites, the FDA will issue either a complete response letter, or CRL, or an approval letter.

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An approval letter, on the other hand, authorizes commercial marketing of the product with specific prescribing information for specific indications.

That is, the approval will be limited to the conditions of use (e.g., patient population, indication) described in the FDA-approved labeling.

That is, the approval will be limited to the conditions of use (e.g., patient

population, indication) described in the FDA-approved labeling.

Further, depending on the specific risk(s) to be addressed, the FDA may require that contraindications, warnings or precautions be included in the product labeling, require that post-approval trials, including Phase 4 clinical trials, be conducted to further assess a product’s safety after approval, require testing and surveillance programs to monitor the product after commercialization or impose other conditions, including distribution and use restrictions or other risk management mechanisms under a REMS which can materially affect the potential market and profitability of the product.

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Under the Ensuring Innovation Act, which was signed into law in April 2021, the FDA must publish action packages summarizing its decisions to approve new drugs and biologics within 30 days of approval of such products.

To date, CRLs are not publicly available documents.

While CRLs were previously treated by the FDA as confidential and were only disclosed in action packages for approved products, the agency announced in September 2025 that it will now release CRLs promptly after they are issued to sponsors.

Since that announcement, the FDA has posted a number of CRLs on its website.

Accelerated Approval Pathway

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In September 2021, the FDA published final regulations which describe the types of evidence that the agency will consider in determining the intended use of a drug or biologic.

On September 9, 2025, President Trump issued a Memorandum directing HHS to “ensure transparency and accuracy in direct-to-consumer prescription drug advertising, including by increasing the amount of information regarding any risks associated with the use of any such prescription drug required to be provided in prescription drug advertisements.” To that end, the FDA announced that it is initiating a rulemaking process “to eliminate the ‘adequate provision’ loophole that allows pharmaceutical advertisements to hide safety information by placing it in another format or location.” In this context, the FDA declared that it will no longer tolerate what it characterized as “deceptive practices” in prescription drug advertising and that the agency would “aggressively deploy” its available enforcement tools, with “heightened scrutiny” of fair balance and disclosures in social media promotions.

The FDA also issued a generic “notice letter” directing companies to “remove any noncompliant advertising and bring all promotional communications into compliance.”

It may be permissible, under very specific, narrow conditions, for a manufacturer to engage in nonpromotional, non-misleading communication regarding off-label information, such as distributing scientific or medical journal information.

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Today, both the PDMA and state laws limit the distribution of prescription pharmaceutical product samples and impose requirements to ensure accountability in distribution.

In November 2013, the Federal Drug Supply Chain Security Act became effective in the U.S., mandating an industry-wide, electronic, interoperable system to trace prescription drugs through the pharmaceutical distribution supply chain with a ten-year phase-in process.

Manufacturers were required by November 2023 to have such systems and processes.

So as not to disrupt supply chains, the FDA has granted certain exemptions from enhanced drug distribution security requirements for eligible trading partners for particular periods of time.

In November 2013, the Federal Drug Supply Chain Security Act, or DSCSA, became effective in the U.S., mandating an industry-wide, electronic, interoperable system to trace prescription drugs through the pharmaceutical distribution supply chain with a ten-year phase-in process.

Manufacturers were required by November 2023 to have such systems and processes, but the FDA has granted certain exemptions from enhanced drug distribution security requirements for eligible trading partners for particular periods of time.

For wholesale drug distributors, the final DSCSA deadline was August 27, 2025, marking the date for mandatory transition to a fully electronic, interoperable system for tracking prescription drugs at the package level throughout the United States.

Generic Drugs and Regulatory Exclusivity

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In support of such applications, a generic manufacturer may rely on the preclinical and clinical testing conducted for a drug product previously approved under an NDA, known as the reference listed drug, or RLD.

Specifically, in order for an ANDA to be approved, the FDA must find that the generic version is identical to the RLD with respect to the active ingredients, the route of administration, the dosage form, the strength of the drug and the conditions of use of the drug.

conditions of use of the drug.

At the same time, the FDA must also determine that the generic drug is “bioequivalent” to the innovator drug.

Under the statute, a generic drug is bioequivalent to a RLD if “the rate and extent of absorption of the drug do not show a significant difference from the rate and extent of absorption of the listed drug.” Upon approval of an ANDA, the FDA indicates whether the generic product is “therapeutically equivalent” to the RLD in its publication “Approved Drug Products with Therapeutic Equivalence Evaluations,” also referred to as the “Orange Book.” Physicians and pharmacists consider a therapeutic equivalent generic drug to be fully substitutable for the RLD.

Upon approval of an ANDA, the FDA indicates whether the generic product is “therapeutically equivalent” to the RLD in its publication “Approved Drug Products with Therapeutic Equivalence Evaluations,” also referred to as the “Orange Book.” Physicians and pharmacists consider a therapeutic equivalent generic drug to be fully substitutable for the RLD.

From time to time, the FDA may issue product-specific guidance regarding RLDs to help clarify its expectations for the content of an ANDA, including requirements for establishing bioequivalence.

Although we are not aware of any prior ANDA approvals for intravitreally administered drugs, the FDA issued what we believe was its first draft product-specific guidance for such a drug in November 2025.

The FDA has also indicated that it plans to issue a draft product-specific guidance for DEXTENZA in February 2026.

Under the Hatch-Waxman Act, the FDA may not approve an ANDA or 505(b)(2) application until any applicable period of non-patent exclusivity for the RLD has expired.

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This three-year exclusivity period often protects changes to a previously approved drug product, such as new indications, dosage forms, route of administration or combination of ingredients.

Three-year exclusivity would be available for a drug product that contains a previously approved active

moiety, provided the statutory requirement for a new clinical investigation is satisfied.

Three-year exclusivity would be available for a drug product that contains a previously approved active moiety, provided the statutory requirement for a new clinical investigation is satisfied.

Unlike five-year NCE exclusivity, an award of three-year exclusivity does not block the FDA from accepting ANDAs or 505(b)(2) NDAs seeking approval for generic versions of the drug as of the date of approval of the original drug product;

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If the ANDA sponsor has provided a Paragraph IV certification to the FDA, the sponsor must also send notice of the Paragraph IV certification to the NDA owner and patent holders once the ANDA has been accepted for filing by the FDA.

The NDA owner and patent holders may then initiate a patent infringement lawsuit in response to the notice of the Paragraph IV certification.

The NDA owner and patent holders

may then initiate a patent infringement lawsuit in response to the notice of the Paragraph IV certification.

The filing of a patent infringement lawsuit within 45 days after the receipt of a Paragraph IV certification automatically prevents the FDA from approving the ANDA or 505(b)(2) NDA until the earliest of 30 months after the receipt of the Paragraph IV notice, expiration of the patent and a decision in the infringement case that is favorable to the ANDA or 505(b)(2) NDA sponsor.

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In addition, the sponsor must show that the biosimilar and reference products have the same mechanism of action for the conditions of use on the label, route of administration, dosage and strength, and the production facility must meet standards designed to assure product safety, purity and potency.

In October 2025, the FDA issued draft guidance which proposes to eliminate the need for sponsors of biosimilar products to conduct comparative human clinical efficacy studies, allowing them to rely instead on analytical testing to demonstrate product differences from a reference product.

For the FDA to approve a biosimilar product as interchangeable with a reference product, the agency must find not only that the product is biosimilar to the reference product but also that it can be expected to produce the same clinical results as the reference product such that the two products may be switched without increasing safety risks or risks of diminished efficacy relative to exclusive use of the reference biologic.

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For biologic products, the six-month period may be attached to any existing regulatory exclusivities but not to any patent terms.

The conditions for pediatric exclusivity include the FDA’s determination that information relating to the use of a new product in the pediatric population may produce health benefits in that population, the FDA making a written request for pediatric clinical trials, and the sponsor agreeing to perform, and reporting on, the requested clinical trials within the statutory timeframe.

The conditions for pediatric exclusivity include the FDA’s

determination that information relating to the use of a new product in the pediatric population may produce health benefits in that population, the FDA making a written request for pediatric clinical trials, and the sponsor agreeing to perform, and reporting on, the requested clinical trials within the statutory timeframe.

This six-month exclusivity may be granted if an NDA sponsor submits pediatric data that fairly respond to a written request from the FDA for such data.

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Class II devices are moderate-risk devices and are subject to the FDA’s general controls, and any other special controls, such as performance standards, post-market surveillance, and FDA guidelines, deemed necessary by the FDA to provide reasonable assurance of the devices’ safety and effectiveness.

Premarket review and clearance by the FDA for Class II devices are accomplished through the 510(k) premarket notification procedure, although some Class II devices are exempt from the 510(k) requirements.

Premarket review and clearance by the FDA for

Class II devices are accomplished through the 510(k) premarket notification procedure, although some Class II devices are exempt from the 510(k) requirements.

Premarket notifications are subject to user fees, unless a specific exemption applies.

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The FDA requires every manufacturer to make the determination regarding the need for a new 510(k) submission in the first instance, but the FDA may review any manufacturer’s decision.

If the FDA disagrees with the manufacturer’s determination and requires new 510(k) clearances or PMA application approvals for modifications to previously cleared products for which the manufacturer concluded that new clearances or approvals are unnecessary, the manufacturer may be required to cease marketing or distribution of the products or to recall the modified product until it obtains clearance or approval, and the manufacturer may be subject to significant regulatory fines or penalties.

be required to cease marketing or distribution of the products or to recall the modified product until it obtains clearance or approval, and the manufacturer may be subject to significant regulatory fines or penalties.

In addition, the FDA is currently evaluating the 510(k) process and may make substantial changes to industry requirements.

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If the FDA’s evaluations are not favorable, the FDA will deny approval of the PMA application or issue a not approvable letter.

The PMA application process, including the

gathering of clinical and nonclinical data and the submission to and review by the FDA, can take several years, and the process can be expensive and uncertain.

The PMA application process, including the gathering of clinical and nonclinical data and the submission to and review by the FDA, can take several years, and the process can be expensive and uncertain.

Moreover, even if the FDA approves a PMA application, the FDA may approve the device with an indication that is narrower or more limited than originally sought.

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An IDE application must be supported by appropriate data, such as animal and laboratory testing results, showing that it is safe to test the device in humans and that the testing protocol is scientifically sound.

An IDE application is considered approved 30 days after it has been received by the FDA, unless the FDA otherwise informs the sponsor prior to 30 calendar days from the date of receipt, that the IDE is approved, approved with conditions, or disapproved.

An IDE application is considered approved 30 days after it has been received by the FDA, unless the FDA otherwise informs the sponsor prior

to 30 calendar days from the date of receipt, that the IDE is approved, approved with conditions, or disapproved.

The FDA typically grants IDE approval for a specified number of subjects to be enrolled at specified study centers.

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Our clinical trials are regulated by the Common Rule, which also includes specific privacy-related provisions.

In addition to federal privacy regulations, there are a number of state laws governing confidentiality and security of health information that may be applicable to our business.

In addition to federal privacy regulations, there are a number of state laws governing confidentiality and security of health information

that may be applicable to our business.

In addition to possible federal civil and criminal penalties for HIPAA violations, state attorneys general are authorized to file civil actions for damages or injunctions in federal courts to enforce HIPAA and seek attorney’s fees and costs associated with pursuing federal civil actions.

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These laws are either in effect or will go into effect sometime before the end of 2026.

Like the CCPA and CPRA, these laws create obligations related to the processing of personal information, as well as special obligations

for the processing of “sensitive” data, which includes health data in some cases.

Like the CCPA and CPRA, these laws create obligations related to the processing of personal information, as well as special obligations for the processing of “sensitive” data, which includes health data in some cases.

Some of the provisions of these laws may apply to our business activities.

There are also states that are strongly considering or have already passed comprehensive privacy laws during the 2024 legislative sessions that will go into effect in 2025 and beyond.

There are also states that are strongly considering additional laws that will go into effect in 2026 and beyond.

Other states will be considering similar laws in the future, and Congress has also been debating passing a federal privacy law.

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For example, the State of Washington passed the My Health My Data Act in 2023 which specifically regulated health information that is not otherwise regulated by the HIPAA rules, and the law also has a private right of action, which further increases the relevant compliance risk.

Connecticut and Nevada have also passed similar laws regulating consumer health data, and more states are considering such legislation in 2024.

Connecticut and Nevada have also passed similar laws regulating consumer health data, and more states are considering such legislation.

These laws may impact our business activities, including our identification of research subjects, relationships with business partners and ultimately the marketing and distribution of our products.

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In order to market any product outside of the United States, a company must also comply with numerous and varying regulatory requirements of other countries and jurisdictions regarding quality, safety and efficacy and governing, among other things, clinical trials, marketing authorization, commercial sales and distribution of drug products.

Whether or not it obtains FDA approval for a product, the company would need to obtain the necessary approvals by the comparable foreign regulatory authorities before it can commence clinical trials or marketing of the product in those countries or jurisdictions.

Whether or not it obtains FDA approval for a product, the company would need to obtain the necessary approvals by the comparable regulatory authorities of foreign countries or economic areas, such as the 27-member European Union, before it can commence clinical trials or marketing of the product in those countries or jurisdictions.

The approval process ultimately varies between countries and jurisdictions and can involve additional product testing and additional administrative review periods.

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Regulatory approval in one country or jurisdiction does not ensure regulatory approval in another, but a failure or delay in obtaining regulatory approval in one country or jurisdiction may negatively impact the regulatory process in others.

The European Union and the European Economic Area, comprised of the European Union member states plus Norway, Iceland, and Liechtenstein, or EEA, applies harmonized regulatory rules for medicinal products, for the approval process and requirements governing the conduct of clinical trials, and for the regulatory approval of medicinal products.

However, pricing and reimbursement for medicinal products varies greatly between countries and jurisdictions and can involve additional testing for health technology assessments.

Non-clinical Studies

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Clinical Trial Approval

On January 31, 2022, the new Clinical Trials Regulation (EU) No 536/2014 became effective in the European Union and replaced the prior Clinical Trials Directive 2001/20/EC.

On January 31, 2022, the Clinical Trials Regulation (EU) No 536/2014, or CTR, became effective in the European Union and replaced the prior Clinical Trials Directive 2001/20/EC, or CTD.

The new regulation aims at simplifying and streamlining the authorization, conduct and transparency of clinical trials in the European Union.

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The submission will be made through the Clinical Trials Information System, a new clinical trials portal overseen by the EMA and available to clinical trial sponsors, competent authorities of the EU Member States and the public.

Beyond streamlining the process, the new Regulation includes a single set of documents to be prepared and submitted for the application as well as simplified reporting procedures for clinical trial sponsors, and a harmonized procedure for the assessment of applications for clinical trials, which is divided in two parts.

Beyond streamlining the process, the CTR includes a single set of documents to be prepared and submitted for the application as well as simplified reporting procedures for clinical trial sponsors, and a harmonized procedure for the assessment of applications for clinical trials, which is divided in two parts.

Part I is assessed by the competent authorities of all EU Member States in which an application for authorization of a clinical trial has been submitted (Member States concerned).

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The role of the relevant ethics committees in the assessment procedure will continue to be governed by the national law of the concerned EU Member State.

However, overall related timelines will be defined by the Clinical Trials Regulation.

The Clinical Trials Regulation, or CTR, foresees a three-year transition period.

The extent to which ongoing and new clinical trials will be governed by the Clinical Trials Regulation varies.

Clinical trials for which an application was submitted (i) prior to January 31, 2022 under the Clinical Trials Directive, or (ii) between January 31, 2022 and January 31, 2023 and for which the sponsor has opted for the application of the Clinical Trials Directive remain governed by said Directive until January 31, 2025.

After this date, all clinical trials (including those which are ongoing) will become subject to the provisions of the CTR.

However, overall related timelines will be defined by the CTR.

The CTR foresaw a three-year transition period.

The extent to which ongoing and new clinical trials were governed by the CTR varies.

Clinical trials for which an application was submitted (i) prior to January 31, 2022 under the CTD, or (ii) between January 31, 2022 and January 31, 2023 and for which the sponsor has opted for the application of the CTD remained governed by the CTD until January 31, 2025.

Since January 31, 2025, all clinical trials (including those which are ongoing) are subject to the provisions of the CTR.

Parties conducting certain clinical trials must, as in the United States, post clinical trial information in the European Union at the EudraCT website:

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Marketing Authorization

To obtain marketing approval of a drug under European Union regulatory systems, a sponsor must submit a marketing authorization application, or MA, either under a centralized or decentralized procedure.

The centralized procedure provides for the grant of a single marketing authorization by the European Commission that is valid for all European Union member states.

To obtain marketing authorization of a drug under European Union regulatory systems, a sponsor must submit a marketing authorization application, or MA, either under a centralized or decentralized procedure/mutual recognition procedure, or MRP.

The centralized procedure provides for the grant of a single marketing authorization by the European Commission that is valid for all EU Member States.

Pursuant to Regulation (EC) No.

726/2004, the centralized procedure is compulsory for specific products, including for medicines produced by certain biotechnological processes, products designated as orphan medicinal products, advanced therapy products and products with a new active substance indicated for the treatment of certain diseases.

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In this circumstance, the EMA ensures that the opinion of the CHMP is given within 150 days.

The decentralized procedure is available to sponsors who wish to market a product in various European Union member states where such product has not received marketing approval in any European Union member states before.

The decentralized procedure provides for approval by one or more other, or concerned, member states of an assessment of an application performed by one member state designated by the sponsor, known as the reference member state.

Under this procedure, a sponsor submits an application based on identical dossiers and related materials, including a draft summary of product characteristics, and draft labeling and package leaflet, to the reference member state and

concerned member states.

The MRP is available to sponsors who wish to market a product in various EU Member States where such product has not received marketing approval in any EU Member States before.

The decentralized procedure provides for approval by one or more other, or concerned, EU Member States of an assessment of an application performed by one member state designated by the sponsor, known as the reference member state, or RMS.

The reference member state prepares a draft assessment report and drafts of the related materials within 210 days after receipt of a valid application.

Within 90 days of receiving the reference member state’s assessment report and related materials, each concerned member state must decide whether to approve the assessment report and related materials.

Within 90 days of receiving the RMS’ assessment report and related materials, each concerned member state must decide whether to approve the assessment report and related materials.

If a member state cannot approve the assessment report and related materials on the grounds of potential serious risk to public health, the disputed points are subject to a dispute resolution mechanism and may eventually be referred to the European Commission, whose decision is binding on all member states.

Conditional Approval

In particular circumstances, European Union legislation (Article 14–a Regulation (EC) No 726/2004 (as amended by Regulation (EU) 2019/5 and Regulation (EC) No 507/2006 on Conditional Marketing Authorizations for Medicinal Products for Human Use) enables sponsors to obtain a conditional marketing authorization prior to obtaining the comprehensive clinical data required for an application for a full marketing authorization.

Conditional Marketing Authorization

In particular circumstances, EU legislation (Article 14–a Regulation (EC) No 726/2004 (as amended by Regulation (EU) 2019/5 and Regulation (EC) No 507/2006 on Conditional Marketing Authorizations for Medicinal Products for Human Use) enables sponsors to obtain a conditional marketing authorization prior to obtaining the comprehensive clinical data required for an application for a full marketing authorization.

Such conditional approvals may be granted for product candidates (including medicines designated as orphan medicinal products) if (1) the product candidate is intended for the treatment, prevention or medical diagnosis of seriously debilitating or life-threatening diseases;

(2) the product candidate is intended to meet unmet medical needs of patients;

(3) a marketing authorization may be granted prior to submission of comprehensive clinical data provided that the benefit of the immediate availability on the market of the medicinal product concerned outweighs the risk inherent in the fact that additional data are still required;

(3) the benefit of the immediate availability on the market of the medicinal product concerned outweighs the risk inherent in the fact that additional data are still required;

(4) the risk-benefit balance of the product candidate is positive, and (5) it is likely that the sponsor will be in a position to provide the required comprehensive clinical trial data.

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Conditional marketing authorizations are valid for one year, and may be renewed annually, if the risk-benefit balance remains positive, and after an assessment of the need for additional or modified conditions or specific obligations.

The timelines for the centralized procedure described above also apply with respect to the review by the CHMP of applications for a conditional marketing authorization, but applicants can also request EMA to conduct an accelerated assessment, for instance in cases of unmet medical needs.

The timelines for the centralized procedure described above also apply with respect to the review by the CHMP of applications for a

conditional marketing authorization, but applicants can also request EMA to conduct an accelerated assessment, for instance in cases of unmet medical needs.

Exceptional Circumstances

A MA may also be granted “under exceptional circumstances” under Article 14(8) of Regulation (EC) No 726/2004 when the applicant can show that it is unable to provide comprehensive data on the efficacy and safety under normal conditions of use even after the product has been authorized and subject to specific procedures being introduced.

An MA may also be granted “under exceptional circumstances” under Article 14(8) of Regulation (EC) No 726/2004 when the applicant can show that it is unable to provide comprehensive data on the efficacy and safety under normal conditions of use even after the product has been authorized and subject to specific procedures being introduced.

This may arise in particular when the intended indications are very rare and, in the present state of scientific knowledge, it is not possible to provide comprehensive information, or when generating data may be contrary to generally accepted ethical principles.

This MA is close to the conditional MA as it is reserved to medicinal products to be approved for severe diseases or unmet medical needs and the applicant does not hold the complete data set legally required for the grant of a MA.

However, unlike the conditional MA, the applicant does not have to provide the missing data and will never have to.

Although the MA “under exceptional circumstances” is granted definitively, the risk-benefit balance of the medicinal product is reviewed annually and the MA is withdrawn in case the risk-benefit ratio is no longer favorable.

Under these procedures, before granting the MA, the EMA or the competent authorities of the European Union Member States make an assessment of the risk-benefit balance of the product on the basis of scientific criteria concerning its quality, safety and efficacy.

Under these procedures, before granting the MA, the EMA or the competent authorities of the EU Member States make an assessment of the risk-benefit balance of the product on the basis of scientific criteria concerning its quality, safety and efficacy.

Periods of Authorization and Renewals

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To this end, the marketing authorization holder must provide the EMA or the competent authority with a consolidated version of the file in respect of quality, safety and efficacy, including all variations introduced since the marketing authorization was granted, at least six months before the marketing authorization ceases to be valid.

The European Commission or the competent authorities of the European Union Member States may decide, on justified grounds relating to pharmacovigilance, to proceed with one further five-year period of marketing authorization.

Once subsequently definitively renewed, the marketing authorization shall be valid for an unlimited period.

Any authorization which is not followed by the actual placing of the medicinal product on the

European Union market (in case of centralized procedure) or on the market of the authorizing European Union Member State within three years after authorization ceases to be valid (the so-called sunset clause).

Once renewed, the marketing authorization is valid for an unlimited period, unless the European Commission or the competent authorities of the European Union Member States decides, on justified grounds relating to pharmacovigilance, to proceed with one further five-year renewal period.

Any authorization which is not followed by the actual placing of the medicinal product on the European Union market (in case of centralized procedure) or on the market of the authorizing European Union Member State within three years after authorization, or if initially placed on the market, is no longer actually present on the market for three consecutive years, ceases to be valid (the so-called sunset clause).

Regulatory Requirements after a Marketing Authorization has been Obtained

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These rules can impose post-authorization studies and additional monitoring obligations.

● The manufacturing of authorized medicinal products, for which a separate manufacturer’s license is mandatory, must also be conducted in strict compliance with the applicable European Union laws, regulations and guidance, including Directive 2001/83/EC, Directive 2003/94/EC, Regulation (EC) No 726/2004 and the European Commission Guidelines for Good Manufacturing Practice.

These requirements include compliance with European Union cGMP standards when manufacturing medicinal products and active pharmaceutical ingredients, including the manufacture of active pharmaceutical ingredients outside of the European Union with the intention to import the active pharmaceutical ingredients into the European Union.

● The marketing and promotion of authorized drugs, including industry-sponsored continuing medical education and advertising directed toward the prescribers of drugs and/or the general public, are strictly regulated in the European Union notably under Directive 2001/83EC, as amended, and European Union Member State laws.

● The manufacturing of authorized medicinal products, for which a separate manufacturer’s license is mandatory, must also be conducted in strict compliance with the applicable EU laws, regulations and guidance, including Directive 2001/83/EC, Directive 2003/94/EC, Regulation (EC) No 726/2004 and the European Commission Guidelines for Good Manufacturing Practice.

These requirements include compliance with EU cGMP standards when manufacturing medicinal products and active pharmaceutical ingredients, including the manufacture of active pharmaceutical ingredients outside of the European Union with the intention to import the active pharmaceutical ingredients into the European Union.

Direct-to-consumer advertising of prescription medicines is prohibited across the European Union.

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Data exclusivity prevents sponsors for authorization of generics of these innovative products from referencing the innovator’s data to assess a generic (abridged) application for a period of eight years.

During an additional two-year period of market exclusivity, a generic marketing authorization application can be submitted and authorized, and the innovator’s data may be referenced, but no generic medicinal product can be placed on the European Union market until the expiration of the market exclusivity.

During an additional two-year period of market exclusivity, a generic marketing authorization application can be submitted and authorized, and the innovator’s data may be referenced, but no generic medicinal product can be placed on the EU market until the expiration of the market exclusivity.

The overall ten-year period will be extended to a maximum of 11 years if, during the first eight years of those ten years, the marketing authorization holder obtains an authorization for one or more new therapeutic indications which, during the scientific evaluation prior to their authorization, are held to bring a significant clinical benefit in comparison with existing therapies.

Even if a compound is considered to be a new chemical entity so that the innovator gains the prescribed period of data exclusivity, another company nevertheless could also market another version of the product if such company obtained marketing authorization based on an MA with a complete independent data package of pharmaceutical tests, preclinical tests and clinical trials.

In this context, it should be noted that the European Union pharmaceutical legislation is currently undergoing a complete review process, in the context of the Pharmaceutical Strategy for Europe initiative, launched by the European Commission in November 2020.

In this context, it should be noted that the EU pharmaceutical legislation is currently undergoing a complete review process, in the context of the Pharmaceutical Strategy for Europe initiative, launched by the European Commission in November 2020.

The European Commission’s proposal for revision of several legislative instruments related to medicinal products was published in April 2023 and includes, among other things, provisions that would potentially reduce the duration of regulatory data protection.

The European Parliament requested several amendments in April 2024.

At this time, the proposed revisions remain to be agreed and adopted by the European Parliament and European Council and the proposals may therefore be substantially revised before adoption, which is not anticipated before early 2026.

The revisions may, however, have a significant impact on the pharmaceutical industry in the long term, if and when adopted.

On December 11, 2025, the European Parliament and Council reached a provisional political agreement on the legislation which is expected to be adopted by mid-2026.

Key changes include updating regulatory data exclusivity to a new system with 8 years data exclusivity and reduced market exclusivity period to 1 year which can be extended if specific conditions are fulfilled, adding launch/supply obligations, incentivizing antibiotic innovation with transferable vouchers, and streamlining approval procedures in the European Union.

If the legislation is finalized in line with the provisional political agreement, it will have a significant impact on the pharmaceutical industry.

Pediatric Exclusivity

If a sponsor obtains a marketing authorization in all European Union Member States, or a marketing authorization granted in the centralized procedure by the European Commission, and the study results for the pediatric population are

included in the product information, even when negative, the medicine is then eligible for an additional six-month period of qualifying patent protection through extension of the term of the Supplementary Protection Certificate, or SPC, or alternatively a one year extension of the regulatory market exclusivity from ten to eleven years, as selected by the marketing authorization holder.

If a sponsor obtains a marketing authorization in all EU Member States, or a marketing authorization granted in the centralized procedure by the European Commission, and the study results for the pediatric population are included in the product information, even when negative, the medicine is then eligible for an additional six-month period of qualifying patent protection through extension of the term of the Supplementary Protection Certificate, or SPC, or alternatively a one year extension of the regulatory market exclusivity from ten to eleven years, as selected by the marketing authorization holder.

Patent Term Extensions

The European Union also provides for patent term extension through SPCs.

The rules and requirements for obtaining a SPC are similar to those in the United States.

An SPC may extend the term of a patent for up to five years after its originally scheduled expiration date and can provide up to a maximum of fifteen years of marketing exclusivity for a drug.

The rules and requirements for obtaining a SPC are set out in Regulation (EC) 469/2009 and are similar to those in the United States.

An SPC may extend the term of a patent right for up to five years after its originally scheduled expiration date and can provide up to a maximum of fifteen years of marketing exclusivity for a drug.

In certain circumstances, these periods may be extended for six additional months if pediatric exclusivity is obtained.

Although SPCs are available throughout the European Union, sponsors must apply on a country-by-country basis.

Although SPCs are available throughout the European Union, sponsors must apply on a country-by-country basis, and SPCs are valid on a country-by-country basis.

Similar patent term extension rights exist in certain other foreign jurisdictions outside the European Union.

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In many countries, including those of the European Union, the pricing of prescription pharmaceuticals is subject to governmental control and access.

In these countries, pricing negotiations with governmental authorities can take considerable time after the receipt of marketing approval for a product.

In these countries, pricing negotiations with governmental authorities can take considerable time after the receipt of marketing

approval for a product.

To obtain reimbursement or pricing approval in some countries, pharmaceutical firms may be required to conduct a clinical trial that compares the cost-effectiveness of the product to other available therapies.

Review and Approval of Medical Devices in the European Union

The European Union has adopted numerous directives and standards regulating, among other things, the design, manufacture, clinical trials, labeling, approval and adverse event reporting for medical devices.

In the European Union, or the European Union, medical devices must comply with the Essential Requirements in Annex I to the currently applicable European Union Medical Devices Directive (Council Directive 93/42/EEC), or the Essential Requirements.

Compliance with these requirements is a prerequisite to be able to affix the CE Mark of Conformity to medical devices, without which they cannot be marketed or sold in the European Economic Area, or EEA, comprised of the European Union member states plus Norway, Iceland, and Liechtenstein.

To demonstrate compliance with the Essential Requirements a manufacturer must undergo a conformity assessment procedure, which varies according to the type of medical device and its classification.

Except for low risk medical devices, where the manufacturer can issue a CE Declaration of Conformity based on a self-assessment of the conformity of its products with the Essential Requirements, a conformity assessment procedure requires the intervention of a third-party organization designated by competent authorities of a European Union country to conduct conformity assessments, or a Notified Body.

Notified Bodies are independent testing houses, laboratories, or product certifiers typically based within the European Union and authorized by the European member states to perform the required conformity assessment tasks, such as quality system audits and device compliance testing.

The Notified Body would typically audit and examine the product’s Technical File and the quality system for the manufacture, design and final inspection of the product before issuing a CE Certificate of Conformity demonstrating compliance with the relevant Essential Requirements.

Medical device manufacturers must carry out a clinical evaluation of their medical devices to demonstrate conformity with the relevant Essential Requirements.

This clinical evaluation is part of the product’s Technical File.

In the EEA, medical devices must comply with the General Safety and Performance Requirements, or SPRs, detailed in Annex I of the EU Medical Devices Regulation (Regulation (EU) 2017/745), or the EUMDR, which came into force in May 2021 and replaced the previously applicable EU Medical Devices Directive (Council Directive 93/42/EEC).

The EUMDR is meant to establish a uniform, transparent, predictable, and sustainable regulatory framework across the European Union for medical devices.

Compliance with SPRs and additional requirements applicable to specific types of devices is a prerequisite to be able to affix the Conformité Européenne mark of conformity, or CE Certificate of Conformity, to medical devices, without which they cannot be marketed or sold in the EEA.

To demonstrate compliance with the SPR and affix the CE mark, manufacturers of medical devices must undergo a conformity assessment procedure, which varies according to the type of medical device and its classification.

Except for low risk medical devices (Class I with no measuring function and which are not sterile), where the manufacturer can issue an EC Declaration of Conformity based on a self-assessment of the conformity of its products with the SPR, a conformity assessment procedure requires the intervention of a third-party organization designated by a competent authority of an EEA country to conduct conformity assessments, or Notified Body.

Depending on the relevant conformity assessment procedure, the Notified Body would audit and examine the Technical File and the quality system for the manufacture, design and final inspection of the devices.

The Notified Body issues a CE Certificate of Conformity following successful completion of a conformity assessment procedure conducted in relation to the medical device and its manufacturer and their conformity with SPR.

The CE Certificate of Conformity entitles the manufacturer to affix the CE mark to its medical devices after having prepared and signed a related EC Declaration of Conformity.

As a general rule, demonstration of conformity of medical devices and their manufacturers with the SPR must be based, among other things, on the evaluation of clinical data supporting the safety and performance of the products during normal conditions of use.

Specifically, a manufacturer must demonstrate that the device achieves its intended performance during normal conditions of use, that the known and foreseeable risks, and any adverse events, are minimized and acceptable when weighed against the benefits of its intended performance, and that any claims made about the performance and safety of the device are supported by suitable evidence This clinical evaluation is part of the product’s Technical File.

A clinical evaluation includes an assessment of whether a medical device’s performance is in accordance with its intended use, and that the known and foreseeable risks linked to the use of the device under normal conditions are minimized and acceptable when weighed against the benefits of its intended purpose.

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Failure to comply with such requirements in a timely manner could result in the withdrawal of the CE Certificate of Conformity and the recall or withdrawal of the subject product from the European market.

A manufacturer must inform the Notified Body that carried out the conformity assessment of the medical devices of any planned substantial changes to the devices which could affect compliance with the Essential Requirements or the devices’ intended purpose.

devices’ intended purpose.

The Notified Body will then assess the changes and verify whether they affect the product’s conformity with the Essential Requirements or the conditions for the use of the devices.

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Promotional materials must also comply with various laws and codes of conduct developed by medical device industry bodies in the European Union governing promotional claims, comparative advertising, advertising of medical devices reimbursed by the national health insurance systems and advertising to the general public.

Additionally, all manufacturers placing medical devices in the market in the European Union are legally bound to report any serious or potentially serious incidents involving devices they produce or sell to the competent authority in whose jurisdiction the incident occurred.

In the European Union, manufacturers must comply with the European Union Medical Device Vigilance System.

Under this system, incidents must be reported to the relevant authorities of the European Union countries, and manufacturers are required to take Field Safety Corrective Actions, or FSCAs, to reduce a risk of death or serious deterioration in the state of health associated with the use of a medical device that is already placed on the market.

An incident is defined as any malfunction or deterioration in the characteristics and/or performance of a device, as well as any inadequacy in the labeling or the instructions for use which, directly or indirectly, might lead to or might have led to the death of a patient or user or of other persons or to a serious deterioration in their state of health.

All manufacturers placing medical devices into the market in the EEA must comply with the EU Medical Device Vigilance System.

Under the EUMDR, incidents must be reported centrally in the EUDAMED database, whose main modules became functional in November 2025 and will become mandatory on May 28, 2026.

Manufacturers are required to take Field Safety Corrective Actions, or FSCAs, to prevent or reduce a risk of death or serious deterioration in the state of health associated with the use of a medical device that is already placed on the market.

An incident is defined as any malfunction or deterioration in the characteristics and/or performance of a device, as well as any inadequacy in the labeling or the instructions for use.

The EUMDR considers "serious incidents" those incidents which, directly or indirectly, led, might lead to or might have led to the death of a patient or user or of other persons a serious deterioration in their state of health, or a serious public health threat.

An FSCA may include the recall, modification, exchange, destruction or retrofitting of the device.

FSCAs must be communicated by the manufacturer or its European Authorized Representative to its customers and to the end users of the device through Field Safety Notices.

The legal framework currently applicable for medical devices in the European Union was amended by Medical Devices Regulation (Regulation (EU) 2017/745) adopted in 2017, which we refer to as the MDR and which repeals and replaces the European Union Medical Devices Directive.

Unlike directives, which must be implemented into the national laws of the European Economic Area, or EEA, member states, the MDR is directly applicable (i.e., without the need for adoption of EEA member State laws implementing them) in all EEA member states and is intended to eliminate current differences in the regulation of medical devices among EEA member states.

The MDR, among other things, is intended to establish a uniform, transparent, predictable and sustainable regulatory framework across the EEA for medical and ensure a high level of safety and health.

The MDR became applicable on May 26, 2021 and will, among other things:

● strengthen the rules on placing devices on the market and reinforce surveillance once they are available;

● establish explicit provisions on manufacturers' responsibilities for the follow-up of the quality, performance and safety of devices placed on the market;

● improve the traceability of medical devices throughout the supply chain to the end-user or patient through a unique identification number;

● set up a central database to provide patients, healthcare professionals and the public with comprehensive information on products available in the European Union;

● strengthen rules for the assessment of certain high-risk devices, such as implants, which may have to undergo an additional check by experts before they are placed on the market.

FSCAs must be communicated by the manufacturer or its legal representative to its customers and/or to the end users of the device through Field Safety Notices.

Brexit and the Regulatory Framework in the United Kingdom

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The IRP is open to applicants that have already received an authorization for the same product from one of the MHRA’s specified Reference Regulators, or RRs.

The RRs notably include EMA and regulators in the EEA member states for approvals in the European Union centralized procedure and mutual recognition procedure as well as the FDA (for product approvals granted in the United States).The RR assessment must have undergone a full and standalone review.

The RRs notably include EMA and regulators in the EEA member states for approvals in the EU centralized procedure and mutual recognition procedure as well as the FDA (for product approvals granted in the United States).

The RR assessment must have undergone a full and standalone review.

RR assessments based on reliance or recognition cannot be used to support an IRP application.

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Compliance with the GDPR is a rigorous and time-intensive process that may increase the cost of doing business or require companies to change their business practices to ensure full compliance.

In July 2020, the Court of Justice of the European Union, or the CJEU, invalidated the European Union-U.S.

In July 2020, the Court of Justice of the European Union, or the CJEU, invalidated the EU-U.S.

Privacy Shield framework, one of the mechanisms used to legitimize the transfer of personal data from the EEA to the United States.

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companies who self-certify to the EU-U.S.

Data Privacy Framework to rely on it as a valid data transfer mechanism for data transfers from the EU to the U.S.

Data Privacy Framework to rely on it as a valid data transfer mechanism for data transfers from the European Union to the U.S.

However, some privacy advocacy groups have already suggested that they will be challenging the EU-U.S.

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Significant uncertainty exists as to the coverage and reimbursement status of products approved by the FDA and other government authorities.

Sales of products will depend, in part, on the extent to which the costs of the products will be covered by third-party payors, including government health programs in the United States such as Medicare and Medicaid, commercial health insurers and managed care organizations.

Sales of products will depend, in part, on the extent to which the costs of the products will be covered by third-party payors, including government healthcare programs in the United States such as Medicare and Medicaid, commercial health insurers and managed care organizations.

The process for determining whether a payor will provide coverage for a product may be separate from the process for setting the price or reimbursement rate that the payor will pay for the product once coverage is approved.

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Section 1833(t)(6) of the Social Security Act provides for temporary additional payments or “transitional pass-through payments” for certain drugs and biological agents.

As originally enacted by the Balanced Budget Refinement Act of 1999, this provision required Centers for Medicare and Medicaid Services, or CMS, to make additional payments to hospitals for current orphan drugs, as designated under section 526 of the FDCA;

As originally enacted by the Balanced Budget Refinement Act of 1999, this provision required the Centers for Medicare and Medicaid Services, or CMS, to make additional payments to hospitals for current orphan drugs, as designated under section 526 of the FDCA;

current drugs and biological agents and brachytherapy sources used for the treatment of cancer;

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However, the pass-through status for J1096 ended on December 31, 2022.

In November 2022, as part of the annual CMS rule-making cycle, the CY 2023 OPPS rule was finalized and provided that DEXTENZA would qualify under the criteria established for non-opioid pain management drugs as a surgical supply provision.

In November 2022, as part of the annual CMS rule-making cycle, the CY 2023 OPPS rule was finalized and provided that DEXTENZA would qualify for separate reimbursement under the criteria established for non-opioid pain management drugs as a surgical supply provision.

This provision allowed for continued separate payment of DEXTENZA in the ASC setting for 2023 but did not require separate payment for DEXTENZA in the HOPD setting.

In November 2023, the CY 2024 OPPS was finalized and confirmed that DEXTENZA would continue to be separately reimbursed in the ASC setting in 2024.

The CY 2025 OPPS rule, which was released in November 2024, allows for

continued separate payment of DEXTENZA in the ASC setting, and it re-establishes the separate payment of DEXTENZA in the HOPD setting.

The CY 2025 OPPS rule, which was released in November 2024, allowed for continued separate payment of DEXTENZA in the ASC setting, and it re-established the separate payment of DEXTENZA in the HOPD setting.

In November 2025, the CY 2026 OPPS was finalized and confirmed that DEXTENZA would continue to be separately reimbursed in the ASC and HOPD settings in 2026.

CPT codes are part of the HCPCS Level I set of procedure codes which consists of codes that are used to report medical services and procedures furnished by physicians.

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In 2024, the Medicare Physician Fee Schedule, or MPFS, for the insertion of DEXTENZA into the canaliculus was $31.43 in the ASCs and $37.33 in the physician’s office for unilateral insertion.

In November 2024, the CY 2025 MPFS rule was finalized resulting in a marginal decrease in physician payments compared to 2024 to $31.38 in the ASCs and HOPDs and $36.88 in the physician’s office for unilateral insertion, due to a decrease in the conversion factor which CMS uses to translate the relative value units, or RVUs, of medical services into fee schedule payment amounts.

In November 2024, the CY 2025 MPFS rule was finalized resulting in a marginal decrease in physician payments compared to 2024 to $31.38 in the ASCs and HOPDs and $36.88 in the physician’s office for unilateral insertion, due to a decrease in the conversion factor, or the Conversion Factor, which CMS uses to translate the relative value units, or RVUs, of medical services into fee schedule payment amounts.

Although the office based RVU for code 68841 was unchanged, the RVU code in the ASC and HOPD setting increased from 0.96 to 0.97.

The CY 2025 MPFS final rule also includes finalized policies for the quality payment program, including the Merit-based Incentive Payment System, or MIPS.

In October 2025, the CY 2026 MPFS rule was finalized resulting in a decrease in RVUs from 0.97 to 0.82 for insertions conducted in the ASC and HOPD setting, and an increase in RVUs from 1.14 to 1.16 for insertions conducted in the physician’s office for unilateral insertion.

The Conversion Factor increased from $32.35 in 2025 to $33.57 in 2026.

The net results of the RVU changes and increased Conversion Factor resulted in a marginal decrease in physician payments compared to 2025 to $27.53 in the ASCs and HOPDs and a marginal increase compared to 2025 to $38.94 in the physician’s office for unilateral insertion.

The CY 2025 MPFS final rule also included finalized policies for the quality payment program, including the Merit-based Incentive Payment System, or MIPS.

For eligible clinicians, CMS calculates the MIPS final score based on four performance categories, which is then used by CMS to determine the payment adjustment applied to the clinicians’ Medicare Part B claims, with clinicians that incur costs above or below national average spending being penalized or incentivized, respectively.

Based on the CY 2025 MPFS final rule, the respective surgeon’s cost for DEXTENZA is included in the MIPS cost performance category for surgeons using DEXTENZA to treat post-surgical ocular inflammation and pain following cataract surgery effective January 1, 2025.

Based on the CY 2025 MPFS final rule, the respective surgeon’s cost for DEXTENZA was included in the MIPS cost performance category for surgeons using DEXTENZA to treat post-surgical ocular inflammation and pain following cataract surgery effective January 1, 2025.

The CY 2026 MPFS rule confirmed the inclusion of DEXTENZA in MIPS for 2026.

In the European Union, pricing and reimbursement schemes vary widely from country to country.

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For example, the European Union provides options for its member states to restrict the range of drug products for which their national health insurance systems provide reimbursement and to control the prices of medicinal products for human use.

European Union member states may approve a specific price for a drug product or it may instead adopt a system of direct or indirect controls on the profitability of the company placing the drug product on the market.

EU Member States may approve a specific price for a drug product or it may instead adopt a system of direct or indirect controls on the profitability of the company placing the drug product on the market.

Other member states allow companies to fix their own prices for drug products, but monitor and control company profits.

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Arrangements with providers, consultants, third-party payors and customers are subject to broadly applicable fraud and abuse and other healthcare laws and regulations.

Such restrictions under applicable federal and state healthcare laws and regulations, include the following:

● the federal Anti-Kickback Statute prohibits, among other things, persons from knowingly and willfully soliciting, offering, receiving or providing remuneration, directly or indirectly, in cash or in kind, to induce or reward either the referral of an individual for, or the purchase, order or recommendation of, any good or service, for which payment may be made, in whole or in part, under a federal healthcare program such as Medicare and Medicaid;

Such restrictions under applicable federal and state healthcare laws and regulations, include, but are not limited to, the following:

● the federal Anti-Kickback Statute , a broad criminal statute, which prohibits , among other things, knowingly and willfully soliciting, offering, receiving or providing remuneration, directly or indirectly, in cash or in kind, to induce or reward either the referral of an individual for, or the purchase, order or recommendation of, any good or service, for which payment may be made, in whole or in part, under a federal healthcare program such as Medicare and Medicaid;

● the federal False Claims Act imposes civil penalties, and provides for civil whistleblower or qui tam actions, against individuals or entities for knowingly presenting, or causing to be presented, to the federal government, claims for payment that are false or fraudulent or making a false statement to avoid, decrease or conceal an obligation to pay money to the federal government;

● the federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, imposes criminal and civil liability for executing a scheme to defraud any healthcare benefit program or making false statements relating to healthcare matters;

● the federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, which, in addition to privacy protections applicable to healthcare providers and other entities, imposes criminal and civil liability for executing a scheme to defraud any healthcare benefit program or making false statements relating to healthcare matters;

● HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act and its implementing regulations, including the Final Omnibus Rule published in January 2013, also imposes obligations, including mandatory contractual terms, with respect to safeguarding the privacy, security and transmission of individually identifiable health information;

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officials for the purpose of obtaining or retaining business or otherwise seeking favorable treatment;

● the federal transparency requirements under the ACA, known as the federal Physician Payments Sunshine Act, will require certain manufacturers of drugs, devices, biologics and medical supplies to report to CMS within the HHS information related to payments and other transfers of value to physicians, other healthcare providers and teaching hospitals and physician ownership and investment interests held by physicians and their immediate family members;

● the federal transparency requirements under the ACA, known as the federal Physician Payments Sunshine Act, which requires certain manufacturers of covered drugs, devices, biologics and medical supplies for which payment is available under Medicare, Medicaid, or the Children’s Health Insurance Program, among others to collect and report to CMS information related to payments and other transfers of value to physicians, other healthcare providers and teaching hospitals and physician ownership and investment interests held by physicians and their immediate family members;

● analogous state and foreign laws and regulations, such as state anti-kickback and false claims laws, may apply to sales or marketing arrangements and claims involving healthcare items or services reimbursed by non-governmental third-party payors, including private insurers.

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Similar healthcare laws and regulations exist in the European Union and other jurisdictions, including reporting requirements detailing interactions with and payments to healthcare providers and laws governing the privacy and security of personal information.

Some state laws require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government in addition to requiring drug manufacturers to report information related to payments to physicians and other health care providers or marketing expenditures.

requiring drug manufacturers to report information related to payments to physicians and other health care providers or marketing expenditures.

State and foreign laws also govern the privacy and security of health information in some circumstances, many of which differ from each other in significant ways and often are not preempted by HIPAA, thus complicating compliance efforts.

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A Joint Select Committee on Deficit Reduction, tasked with recommending a targeted deficit reduction of at least $1.2 trillion for the years 2013 through 2021, was unable to reach required goals, thereby triggering the legislation’s automatic reduction to several government programs.

These changes included aggregate reductions to Medicare payments to providers of up to 2% per fiscal year, which went into effect in April 2013 and will remain in effect through 2031.

These changes included aggregate reductions to Medicare payments to providers of up to 2% per fiscal year, which went into effect in April 2013 and, due to subsequent statutory amendments, will remain in effect through the first eleven months of the President’s fiscal year 2032 sequestration order unless additional congressional action is taken, with the exception of a temporary suspension, and later a temporary reduction instituted during the COVID-19 pandemic that expired on July 1, 2022.

Since enactment of the PPACA, there have been, and continue to be, numerous legal challenges and Congressional actions to repeal and replace provisions of the law.

For example, with enactment of the Tax Cuts and Jobs Act of 2017, or the Tax Act, which was signed by President Trump on December 22, 2017, Congress repealed the “individual mandate.” The repeal of this provision, which requires most Americans to carry a minimal level of health insurance, became effective in 2019.

On December 14, 2018, a U.S.

District Court judge in the Northern District of Texas ruled

that the individual mandate portion of the PPACA is an essential and inseverable feature of the PPACA, and therefore because the mandate was repealed as part of the Tax Act, the remaining provisions of the PPACA are invalid as well.

Supreme Court heard this case on November 10, 2020 and, on June 17, 2021, dismissed this action after finding that the plaintiffs do not have standing to challenge the constitutionality of the ACA.

Litigation and legislation over the PPACA are likely to continue, with unpredictable and uncertain results.

On June 17, 2021, the U.S.

Supreme Court dismissed a judicial challenge to the PPACA brought by several states who argued that, without the individual mandate, the entire PPACA was unconstitutional.

The Supreme Court’s dismissal of the lawsuit did not specifically rule on the constitutionality of the ACA.

Litigation and legislation over the PPACA may continue, with unpredictable and uncertain results.

Pharmaceutical Prices

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The state will also need to relabel the products and perform quality testing of the products to meet FDA standards.

Further, on November 20, 2020, HHS finalized a regulation removing safe harbor protection for price reductions from pharmaceutical manufacturers to plan sponsors under Part D, either directly or through pharmacy benefit managers, unless the price reduction is required by law.

The final rule would eliminate the current safe harbor for Medicare drug rebates and create new safe harbors for beneficiary point-of-sale discounts and pharmacy benefit manager, or PBM, service fees.

It originally was set to go into effect on January 1, 2022, but with passage of the Inflation Reduction Act, or IRA, has been delayed by Congress to January 1, 2032.

More recently, on August 16, 2022, the IRA was signed into law by President Biden.

The new legislation has implications for Medicare Part D, which is a program available to individuals who are entitled to Medicare Part A or enrolled in Medicare Part B to give them the option of paying a monthly premium for outpatient prescription drug coverage.

Among other things, the IRA requires manufacturers of certain drugs to engage in price negotiations with Medicare (beginning in 2026), with prices that can be negotiated subject to a cap;

imposes rebates under Medicare Part B and Medicare Part D to penalize price increases that outpace inflation (first due in 2023);

and replaces the Part D coverage gap discount program with a new discounting program (beginning in 2025).

On May 21, 2025, the FDA announced that it would offer individual states the opportunity to submit draft proposals for pre-review and meet with the agency to obtain initial feedback from FDA prior to formally submitting their Section 804 importation program (SIP) proposals.

The intent of these meetings is to assist states in developing their proposals by further clarifying requirements, enhancing the quality of proposals submitted to the agency and ultimately shortening the review timeline.

More recently, on August 16, 2022, the Inflation Reduction Act of 2022, or IRA, was signed into law by former President Biden.

The legislation requires manufacturers of certain drugs to engage in price negotiations with Medicare, with prices that can be negotiated subject to a cap;

imposes rebates under Medicare Part B and Medicare Part D to penalize price increases that outpace inflation;

and replaces the Part D coverage gap discount program with a new discounting program.

The IRA permits the Secretary of the HHS to implement many of these provisions through guidance, as opposed to regulation, for the initial years.

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CMS may negotiate prices for ten high-cost drugs paid for by Medicare Part D starting in 2026, followed by 15 Part D drugs in 2027, 15 Part B or Part D drugs in 2028, and 20 Part B or Part D drugs in 2029 and beyond.

This provision applies to drug products that have been approved for at least 9 years and biologics that have been licensed for 13 years, but it does not apply to drugs and biologics that have been approved for a single rare disease or condition.

This provision applies to drug products that have been approved for at least 9 years and biologics that have been licensed for 13 years.

When originally enacted, the IRA explicitly excluded from price negotiation orphan drugs designated for only one rare disease or condition and for which the only active approved indication is for such disease or condition.

However, the One Big Beautiful Bill Act signed into law on July 4, 2025 amended the applicable statute to broaden the orphan drug exclusion to include products with more than one orphan designation and more than one approved indication.

Further, the legislation subjects drug manufacturers to civil monetary penalties and a potential excise tax for failing to comply with the legislation by offering a price that is not equal to or less than the negotiated “maximum fair price” under the law or for taking price increases that exceed inflation.

The legislation also requires manufacturers to pay rebates for drugs in Medicare Part D whose price increases exceed inflation.

The new law also caps Medicare out-of-pocket drug costs at an estimated $4,000 a year in 2024 and, thereafter beginning in 2025, at $2,000 a year.

The legislation also requires manufacturers to pay rebates for drugs in Medicare Part B and D whose price increases exceed inflation.

The law also capped Medicare beneficiary out-of-pocket drug costs at $4,000 per year in 2024 and, $2,000 a year from 2025 onwards.

The first cycle of negotiations for the Medicare Drug Price Negotiation Program commenced in the summer of 2023.

On August 15, 2024, the HHS published the results of the first Medicare drug price negotiations for ten selected

drugs that treat a range of conditions, including diabetes, chronic kidney disease, and rheumatoid arthritis.

The prices of these ten drugs will become effective January 1, 2026.

On January 17, 2025, CMS announced its selection of 15 additional drugs covered by Part D for the second cycle of negotiations by February 1, 2025.

While there had been some questions about the Trump Administration’s position on this program, CMS issued a public statement on January 29, 2025, declaring that lowering the cost of prescription drugs is a top priority of the new administration and CMS is committed to considering opportunities to bring greater transparency in the negotiation program.

The second cycle of negotiations with participating drug companies will occur during 2025, and any negotiated prices for this second set of drugs will be effective starting January 1, 2027.

In June 2023, Merck & Co.

filed a lawsuit against HHS and CMS asserting that, among other things, the IRA’s Drug Price Negotiation Program for Medicare constitutes an uncompensated taking in violation of the Fifth Amendment of the Constitution.

Subsequently, a number of other parties, including the U.S.

Chamber of Commerce, Bristol Myers Squibb Company, PhRMA, Astellas, Novo Nordisk, Janssen Pharmaceuticals, Novartis, AstraZeneca and Boehringer Ingelheim, also filed lawsuits in various courts with similar constitutional claims against HHS and CMS.

HHS has generally won the substantive disputes in these cases, and various federal district court judges have expressed skepticism regarding the merits of the legal arguments being pursued by the pharmaceutical industry.

Certain of these cases are now on appeal and, on October 30, 2024, the Court of Appeals for the Third Circuit heard oral argument in three of these cases.

Litigation involving these and other provisions of the IRA will continue with unpredictable and uncertain results.

On August 15, 2024, the HHS published the results of the first Medicare drug price negotiations for ten selected drugs that treat a range of conditions, including diabetes, chronic kidney disease, and rheumatoid arthritis.

The prices of these ten drugs became effective January 1, 2026.

On January 17, 2025, CMS announced its selection of 15 additional drugs covered by Part D for the second cycle of negotiations, and on November 25, 2025, CMS released negotiated prices for such products that will go into effect beginning January 1, 2027.

While it remains to be seen how the drug pricing provisions imposed by the IRA will affect the broader pharmaceutical industry, several pharmaceutical manufacturers and other industry stakeholders have challenged the law, including through lawsuits brought against the HHS, the Secretary of the HHS, CMS, and the CMS Administrator challenging the constitutionality and administrative implementation of the IRA’s drug price negotiation provisions.

This litigation is ongoing and the results, and potential impacts on our business, are uncertain.

The current presidential administration has indicated that reducing prescription drug prices will be a focus, with CMS issuing a public statement on January 29, 2025, declaring that lowering the cost of prescription drugs is a top priority of the new administration and CMS is committed to considering opportunities to bring greater pricing transparency.

Moreover, President Trump has signed multiple executive orders addressing prescription drug pricing and access, including:

on April 15, 2025, outlining several actions the Secretary of the Department of HHS must take to optimize healthcare regulations that will provide access to prescription drugs at lower costs;

on May 5, 2025, aiming to promote domestic production of critical medicines;

and on May 12, 2025, aiming to establish a “most favored nation” drug pricing policy that would tie U.S.

drug prices to the prices paid for drugs in other countries.

Since the May 12, 2025 “most favored nation” executive order, the Trump administration has continued to exert pressure on drug manufacturers to implement “most favored nation” pricing, including by suggesting that the administration may impose significant tariffs on pharmaceuticals if such manufacturers do not reach agreements to implement “most favored nation” pricing.

Additionally, in November 2025, CMS announced a new voluntary payment initiative called the GENEROUS Model (GENErating cost Reductions for U.S.

Medicaid Model) where drug manufacturers may voluntarily offer supplemental rebates to participating state Medicaid programs that are intended to provide such Medicaid programs with a “most favored nation” price for participating manufacturers’ products.

On December 23, 2025, CMS, through its Center for Medicare and Medicaid Innovation, or CMMI, proposed two five-year pilot programs to implement a “reference pricing” model for drugs paid for under Medicare for 25% of covered beneficiaries.

The programs are referred to as the Global Benchmark for Efficient Drug Pricing Model for Medicare Part B drugs, referred to as GLOBE, and the Guarding U.S.

Medicare Against Rising Drug Costs for Medicare Part D drugs, referred to as GUARD.

Under the proposed rules, a manufacturer would owe rebates to Medicare if prices for their drugs exceeded the prices paid by other economically comparable reference countries (with an initial list of 19 reference countries included in the proposed rule).

Comments are due on the proposed pilot program rules on or before February

23, 2026, and the pilot programs are proposed to go into effect beginning October 1, 2026.

It remains to be seen how these drug pricing initiatives will affect the broader pharmaceutical industry.

At the state level, individual states are increasingly aggressive in passing legislation and implementing regulations designed to control pharmaceutical and biological product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some cases, designed to encourage importation from other countries and bulk purchasing.

A number of states, for example, require drug manufacturers and other entities in the drug supply chain, including health carriers, pharmacy benefit managers, wholesale distributors, to disclose information about pricing of pharmaceuticals, including, but not limited to, information in connection with new product launches that exceed certain levels as identified in the relevant statutes.

This is increasingly true with respect to products approved pursuant to the accelerated approval pathway.

12 unchanged sentences

The development, attraction and retention of employees is a critical success factor for us for the execution of our business strategy and succession planning.

To support the advancement of our employees, we offer training and development programs encouraging advancement from within and continue to fill our team with strong and experienced

management talent.

To support the advancement of our employees, we offer training and development programs encouraging advancement from within and continue to fill our team with strong and experienced management talent.

We leverage both formal and informal programs to identify, foster, and retain top talent at both the corporate and operating unit level.

4 unchanged sentences

We were incorporated under the laws of the State of Delaware in 2006.

Our principal executive offices are located at 15 Crosby Drive, Bedford, MA 01730, and our telephone number is (781) 357-4000.

Our manufacturing is located at 36 Crosby Drive, Suite 101, Bedford, MA 01730 and our research and development operations are located at 15 Crosby Drive, Bedford, MA 01730.

Our principal executive offices are located at 15 Crosby Drive, Bedford, MA 01730, or 15 Crosby Drive, and our telephone number is (781) 357-4000.

Our research and development operations and our manufacturing for AXPAXLI are located at 15 Crosby Drive.

Our manufacturing for DEXTENZA is located at 36 Crosby Drive, Suite 101, Bedford, MA 01730.

Our website address is www.ocutx.com.

5 unchanged sentences

Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 1. Business