Q4 2024 Ocular Therapeutix Inc Earnings Call

Operator: and Business Results.

Operator: During today's call, certain statements we will be making constitute forward-looking statements under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Actual results may differ materially as a result of a variety of factors, including risks and uncertainties identified in the risk factors section of our annual report on Form 10-K and our other SEC files.

During today's call certain statements, we will be making constitute forward looking statements under the safe Harbor provisions of the private Securities Litigation Reform Act of 1095.

Actual results may differ materially as a result of a variety of factors, including risks and uncertainties identified in the risk factors section of our annual report on Form 10-K, and our other SEC filings.

Pravin Dugel: With that, I'd like to hand the call over to Dr. Pravin Dugel to review our recent updates. Thank you, Bill, and thank you to everyone for joining us today.

Speaker Change: With that I'd like to hand, the call over to Dr. Praveen Dougal to review our recent updates prevented.

Praveen Dougal: Thank you Bill.

Speaker Change: Thank you to everyone for joining us today.

Pravin Dugel: 2024 was a transformational year for Ocular Therapeutix. We sharpened our focus and embraced a single, bold mission. to redefine the retina experience. Today, disrupting the treatment paradigm in wet AMD is our top priority. and we're executing with speed, precision, and confidence. to bring Ex-Paxly to patients who need a more sustainable and effective treatment option. Despite established and effective treatments for wet AMD, the burden of frequent dosing leads up to a 40 percent of patients discontinuing treatment in the first year alone, effectively allowing themselves to go blind.

Speaker Change: 2024 was a transformational year for ocular therapeutics, we sharpened our focus and embraced a single old mission.

Speaker Change: To redefine the retina experience.

Speaker Change: Today.

Speaker Change: Disrupting the treatment paradigm in wet AMD is our top priority.

Speaker Change: And we are executing with speed precision and confidence to.

Speaker Change: To bring ex tax lead to patients who need a more sustainable and effective treatment option.

Speaker Change: Despite established and effective treatments for wet AMD the burden of frequent dosing leads up to a 40% of patients discontinuing treatment in the first year alone effectively allowing themselves to go blind.

Pravin Dugel: Patients Deserve Better. and Paxily has the potential to become the standard of care by offering a long-lasting, flexible treatment option. and What AMD is Just the Beginning.

Speaker Change: Patients deserve better.

Speaker Change: <unk> has the potential to become the standard of care by offering a long lasting flexible treatment option.

Speaker Change: And what AMD is just the beginning.

Pravin Dugel: With compelling early clinical results in nonproliferative diabetic retinopathy and diabetic macular edema, we see a significant opportunity to expand into these and other highly prevalent retinal indications where millions of patients remain untreated.

Speaker Change: With compelling early clinical results and non proliferative diabetic retinopathy diabetic macular edema we.

Speaker Change: We see a significant opportunity to expand into these and other highly prevalent retinal indications where millions of patients to remain untreated.

Pravin Dugel: This morning, we announced several exciting updates that enhance and accelerate our registrational program for Expasely, positioning us incredibly well as we move toward clinical data and a potential NDA submission. Let's get right to it. First... We recently received FDA approval for an amendment to our special protocol agreement for SOAR 1 that incorporates redosing in all patients at week 52 and week 76. We believe this amendment unlocks the potential for X-Paxly to secure an unprecedented 6-12 month dosing label in wet AMD, showcasing what we believe to be best-in-class durability. The impact of this cannot be overstated.

Speaker Change: This morning, we announced several exciting updates that enhance and accelerate our Registrational program Flagstaff fleet positioning us incredibly well as we move toward clinical data and a potential NDA submission.

Speaker Change: Let's get right to it.

Speaker Change: First.

Speaker Change: We recently received FDA approval for an amendment to our special protocol agreement for so one that incorporates re dosing in all patients at week 52 and week 76.

Speaker Change: We believe this amendment unlocks the potential break stacks late to secure an unprecedented six to 12 months dosing label in wet AMD showcasing what we believe to be best in class durability.

Speaker Change: The impact of this cannot be overstated.

Pravin Dugel: The most recent approvals in this indication extend durability by about two weeks in most patients. Yet, they have rapidly gained market share and generated significant revenues in a very short period of time. With XPAXLY, we're talking about a different orbit altogether, with the potential to extend durability by months. As part of this amendment, the 36-week primary endpoint for SOAR 1 remains unchanged. but we're required to maintain masking until week 52 to provide additional information on durability up to and to allow potential label permitting redosing at 12 months. As a result, we now expect to report top-line data in the first quarter of 2026.

Speaker Change: The most recent approvals in this indication extend durability by about two weeks in most patients yet.

Speaker Change: Rapidly gained market share and generated significant revenue in a very short period of time.

Speaker Change: With <unk>, we're talking about a different or but altogether.

Speaker Change: With the potential to extend durability by months.

Speaker Change: As part of this amendment the 36 week primary endpoint for sold one remains unchanged.

Speaker Change: But we are required to maintain lasting until week 52 to provide additional information on durability up to <unk>.

Speaker Change: To allow potential label permitting be dosing at 12 months.

Speaker Change: As a result, we now expect to report topline data in the first quarter of 2026.

Pravin Dugel: While this slightly shifts the timeline for SOL1 top-line data, we believe the long-term benefits of this strategy are tremendous. and we'll be abundantly clear at the end of this call. Most importantly, this strategy should allow us to accelerate our timeline for a comprehensive regulatory submission for X-TAC's lead in wet AMD, as I will describe. Moreover, we expect the additional data for repeat dosing will provide valuable insights into expats' extended durability. potentially supporting even greater flexibility on the product label. Sol1, a trial that many thought would never be enrolled, completed randomization in December 2024, well ahead of expectations, with 344 subjects randomized across more than 100 clinical sites in the U.S.

Speaker Change: While this slightly shifts the timeline for sold one topline data we believe the long term benefits of this strategy are tremendous.

Speaker Change: And we'll be abundantly clear at the end of this call.

Speaker Change: Most importantly, this strategy should allow us to accelerate our timeline for a comprehensive regulatory submission for its tax late and wet AMD as I will describe.

Speaker Change: Moreover, we expect the additional data for repeat dosing will provide valuable insights into expectedly extended durability.

Speaker Change: Potentially supporting even greater flexibility on the product label.

Speaker Change: So one a file that many thought would never be enrolled completed randomization in December 2024, well ahead of expectations with 344 subjects randomized across more than 100 clinical sites in the U S and Argentina.

Pravin Dugel: and Argentina. Trial conduct is now our top priority. We are thrilled to report that subject retention has been exceptional to date. And the vast majority of rescue treatments, as we have reviewed on a mass basis, remain in line with the pre-specified criteria established in the SOLE1 protocol. We have also optimized SOLAR, our non-inferiority study, to align with the changes in SOL1. Because re-dosing is now incorporated into SOL1 and retention in the trial is exceptional to date, we are reducing the size of SOLAR from 825 subjects to approximately 555 subjects, randomized. while maintaining robust statistical power of 90% to evaluate a primary endpoint based on our expectations of how expats will perform.

Speaker Change: Trial conduct is now our top priority.

Speaker Change: We are thrilled to report that subject retention has been exceptional to date.

Speaker Change: And the vast majority of rescue treatments as we have reviewed on a mass basis remain in line with the pre specified criteria established in the so one protocol.

Speaker Change: We have also optimized so laura or non inferiority study to align with the changes and sold one.

Speaker Change: Because re dosing is now incorporated and so one.

Speaker Change: And retention in the trial is exceptional to date, we are reducing the size. So large 825 subjects to approximately 555 subjects.

Speaker Change: Randomized.

Speaker Change: While maintaining robust statistical power up 90% to evaluate our primary endpoint based on our expectations of how X tactfully will perform.

Pravin Dugel: So LAR was initially designed to include 825 subjects to meet the minimum FDA requirements to receive an unrestricted label fully dosing. Now that subjects in SOAR 1 are also being re-dosed, we're afforded the flexibility to reduce the number of subjects in SOAR. This reduction should accelerate the SOLAR timeline for reporting data, enhance capital efficiency, and maintain the scientific rigor needed for regulatory approval. Remember that SOLAR is a non-inferiority trial comparing expasely administered every 24 weeks against 2 mg of Flipraset administered every 8 weeks. The primary endpoint is the mean change in best corrected visual acuity, or BCVA, at week 56.

Speaker Change: So Laura was initially designed to include 825 subjects to meet the minimum FTE requirements to receive an unrestricted label for re dosing.

Speaker Change: Now the subjects and sold one are also being re dose were afforded the flexibility to reduce the number of subjects and so law.

Speaker Change: This reduction should accelerate the sole or timeline for reporting data enhanced capital efficiency and maintain the scientific rigor needed for regulatory approval.

Speaker Change: Remember that solar is a non inferiority trial comparing ex taxi administered every 24 weeks against two milligram a flipper set administered every eight weeks.

Speaker Change: The primary endpoint is the mean change in best corrected visual acuity or.

Speaker Change: Or B C. D E at week 56, and patients will be followed until week 104 for safety.

Pravin Dugel: and patients will be followed until week 104 for safety. Importantly, as per the protocol agreed to by the FDA, the non-inferiority margin for the expatsly arm at the lower bound is minus 4.5 letters of mean BCVA when compared to two milligram of Fliverset dose every eight weeks. This is also in line with the FDA's draft guidance. which we are adhering to by incorporating an eight milligram of Fliverset masking comparator arm with the exact same dosing frequency as the expaxillary arm. Additionally, our pre-specified supplemental injection criteria are strategically designed to ensure trial integrity and preserve clinical relevance.

Speaker Change: Importantly.

Speaker Change: As per the protocol agreed to by the FDA the non inferiority margin for the ex constantly arm at the lower bound is minus 4.5 letters of mean D. C V. A when compared to two milligram flipper set dose every eight weeks.

Speaker Change: This is also in line with the Fda's draft guidance, which.

Speaker Change: Which we are adhering to by incorporating an eight milligram a flipper set masking comparator arm with the exact same dosing frequency as the <unk>.

Speaker Change: Additionally, our prespecified supplemental injection criteria are.

Speaker Change: Our strategically designed to ensure trial integrity and preserve clinical relevance.

Pravin Dugel: These criteria are consistent with previous non-inferiority studies and include a combination of vision loss and OCT changes. by aligning these standard non-inferiority trial rescue protocols. We believe the SOLAR study remains well-positioned to demonstrate expactly durability and effectiveness in a repeat dosing setting. Solar enrollment continues to be strong. We previously announced 311 subjects enrolled across various stages of loading and randomization as of January 10, 2025. This momentum puts us in a great position to advance our registrational program efficiently and effectively. here at Ocular. Our clinical trial design strategy, using the loading phase to select patients for randomization and thereby potentially de-risking our patient populations, has been a key differentiator.

These criteria are consistent with previous non inferiority studies and include a combination of vision loss and <unk> changes.

Speaker Change: By aligning these standard non inferiority trial rescue protocols.

Speaker Change: We believe the solar study remains well positioned to demonstrate ex Tac sleep durability and effectiveness in a repeat dosing study.

Speaker Change: So Laura enrollment continues to be strong.

Speaker Change: We previously announced.

Speaker Change: 311 subjects enrolled across various stages of loading and randomization as of January 10, 2025.

Speaker Change: This momentum puts us in a great position to advance our Registrational program efficiently and effectively.

Speaker Change: Here at ocular.

Speaker Change: Our clinical trial design strategy, using the loading phase to select patients for randomization, and thereby potentially derisking our patient populations has been a key differentiator.

Pravin Dugel: We designed SOL1 and SOLR to work together, with each trial seeking to answer critical questions about X-PAX's durability, repeatability, and flexibility. These studies were developed to be complementary and not redundant, ensuring that together they provide a robust clinical data set that could support both regulatory approval and commercial adoption. So one is focused on durability, evaluating whether a single dose of expaxonate can maintain vision for 36 weeks compared to a single two milligram of flibberset injection. This study was designed to establish superiority and to set a new benchmark for long-term efficacy in wet AMD treatment. with the recent spa amendment incorporating 52-week and 76-week redosing.

Speaker Change: We designed so one is so large to work together with each trial seeking too and so critical questions about ex tax lien durability repeatability.

Speaker Change: And flexibility.

Speaker Change: These studies were developed to be complementary and not redundant ensuring that together they provide a robust clinical dataset that could support both regulatory approval and commercial adoption.

Speaker Change: So one is focused on durability evaluating whether a single dose of <unk> actually can maintain vision for 36 weeks compared to a single two milligram a flipper set injection.

Speaker Change: This study was designed to establish superiority and to set a new benchmark for long term efficacy in wet AMD treatment.

Speaker Change: With the recent Spa Amendment, incorporating 52 week and 76 week re dosing.

Pravin Dugel: So one now also provides important insights into extended treatment intervals and long-term redosing potential. SOLAR, on the other hand, is designed to address more frequent repeat dosing and potential real-world applicability. by comparing expats every 24 weeks. to 2mg of Flibrisat every 8 weeks so LAR evaluates how expats sleep performs relative to a common but burdensome treatment regimen. The study is structured to provide critical evidence supporting the feasibility of an every-six-month treatment paradigm. one that we believe is aligned to preferences of retinal specialists and that could dramatically reduce the burden of care for patients and caregivers alike.

Speaker Change: So one now also provide important insights into extended treatment intervals and long term re dosing potential.

Speaker Change: So la on the other hand is designed to address more frequent repeat dosing and potential real world applicability.

Speaker Change: By comparing X tactically every 24 weeks to two milligram flipper set every eight weeks. So lar evaluates how extensively performs relative to a common but burdensome treatment regimen.

Speaker Change: The study is structured to provide critical evidence supporting the feasibility of an every six months treatment paradigm.

Speaker Change: One that we believe is aligned to preferences of retinal specialists and that could dramatically reduce the burden of care for patients and caregivers alike.

Pravin Dugel: Both studies were thoughtfully aligned with regulatory guidance. So one supported by SPA and Solar validated by type C written response received from the FDA in August 2024, along with a subsequent written response received from the FDA in December 2024. Importantly, neither study utilizes sham for masking, adhering to the FDA's clear stance that sham can introduce bias, expressed through the agency's written feedback and public comments. The FDA previously agreed that TOGETHER, SOL1, and SOLAR could constitute two adequate and well-controlled trials to support a potential NDA and label for expaxly in wet AMD. Pending a successful outcome, we intend to submit our NDA after the SOLAR 56-week primary endpoint is reached.

Speaker Change: Both studies were thoughtfully aligned with regulatory guidance.

Speaker Change: So one supported by Spa and so lar validated by the written response, we received from the FDA in August 2024, along with a subsequent written response received from the FDA in December 2024 importantly.

Speaker Change: Importantly, neither study utilizes sham for masking.

Speaker Change: And hearing to the F D. A clear stance that sham can't introduce bias expressed through the agency's written feedback.

Speaker Change: In public comments.

Speaker Change: The FDA previously agreed that together, so one and so Laura could constitute two adequate and well controlled trials to support a potential NDA and label for <unk> in wet AMD.

Speaker Change: Pending a successful outcome, we intend to submit our NDA after the sole or 56 week primary end point is reached.

Pravin Dugel: By integrating these complementary approaches seeking to demonstrate both best-in-class durability in SOL1 and sustained repeat dosing in SOLAR, we believe we are enhancing the potential for successful trials that support a differentiated, commercially attractive label. The dual nature of these trials allow us to generate a comprehensive clinical data set that has the potential to support a strong regulatory submission and a compelling value proposition for patients, retina specialists, and payers. Beyond WET-AMD, we see a tremendous opportunity for Expaxly in non-proliferative diabetic retinopathy, or NPDR, and diabetic macular edema, or DME. Diabetic retinopathy is the leading cause of blindness in the working age population in the U.S.

Speaker Change: By integrating these complementary approaches seeking to demonstrate both best in class durability and sold one and sustained repeat dosing and so Laura.

Speaker Change: We believe we are enhancing the potential for successful trials that support a differentiated commercially attractive label.

Speaker Change: The dual nature of these trials will allow us to generate a comprehensive clinical data set that has the potential to support a strong regulatory submission and a compelling value proposition for patients retinal specialists and payors.

Speaker Change: Beyond wet AMD, we see a tremendous opportunity for <unk> in non proliferative diabetic retinopathy or M. P D R and diabetic macular edema or DNA.

Speaker Change: Diabetic retinopathy is the leading cause of blindness in the working age population in the U S. Despite the availability of anti VEGF therapy fewer than 1% of.

Pravin Dugel: Despite the availability of anti-VEGF therapies, fewer than 1% of the 6.3 million NPDR patients in the U.S. receive treatment today, largely due to the burden of frequent injection. X-FACTS really has the potential to transform this landscape. Our proof-of-concept helios trial demonstrated compelling results for expactly in both NPDR and DME. In this trial, we showed that a single expaxillary injection may prevent vision-threatening complications for up to 12 months. Additionally, all patients in the expatriate arm that had DME saw improvement at week 48. So what does this mean? That means that I, as a retina physician, can say to a patient, Your risk with diabetic retinopathy of developing vision-threatening complication year upon year is 30 to 40%.

Speaker Change: Of the $6 3 million N P D oar patients in the U S receive treatment today, largely due to the burden of frequent injections.

Speaker Change: <unk> has the potential to transform this landscape.

Speaker Change: Our proof of concept Helios trial demonstrated compelling results for <unk> in both N P D R and D E.

Speaker Change: In this trial, we showed that a single <unk> injection may prevent vision threatening complications for up to 12 months.

Speaker Change: Additionally, all patients in the <unk> arm that had DNV saw improvement at week 48.

Speaker Change: So what does this mean.

Speaker Change: That means that I as a retina physicians can say to a patient.

Speaker Change: Your risk with diabetic retinopathy of developing vision threatening complications euro upon year is 30% to 40%. However.

Pravin Dugel: However, if you come to see me just once or twice a year, much like you go to a dentist for teeth cleaning, I may be able to reduce that risk to almost zero.

Speaker Change: If you come to see me.

Speaker Change: Just once or twice a year much like you go to a dentist for teeth cleaning.

Speaker Change: I may be able to reduce that risk to almost zero.

Pravin Dugel: That is a powerful message.

Speaker Change: That is.

Speaker Change: Is a powerful message.

Pravin Dugel: I'm happy to inform you today that we expect to receive FDA feedback on our clinical trial design for NPDR and DME in the first half of this year, paving the way for our next steps in these important indications. Following the receipt of the FDA feedback, we look forward to sharing with you our clinical trial design for these underserved, vision-threatening indications.

Speaker Change: I'm happy to inform you today that we expect to receive FDA feedback on our clinical trial design for N. P. D R and D N E.

Speaker Change: In the first half of this year paving the way for our next steps in these important indications.

Speaker Change: Following receipt of the FDA feedback, we look forward to sharing with you our clinical trial design for these underserved.

Speaker Change: Vision threatening indications.

Pravin Dugel: We continue to operate from a position of financial strength with a cash balance of $392 million as of December 31st, 2024. We remain laser focused on execution of SOL1 and SOLR. Our disciplined and prudent approach means that we are well-financed and believe we have sufficient cash to fund our planned operating expenses, debt service obligations, and capital expenditures into 2028, fully funding our registrational trials and wet AMD, and leaving us well-positioned to execute on our broader strategic objectives.

Speaker Change: We continue to operate from a position of financial strength with a cash balance of $392 million as of December 31.

Speaker Change: 2024.

Speaker Change: We remain laser focused on execution of so one and so Laura.

Speaker Change: Our disciplined and prudent approach means that we are well financed and believe we have sufficient cash to fund our planned operating expenses debt service obligations.

Speaker Change: And capital expenditures into 2028 fully funding all registrational trials in wet AMD, and leaving us well positioned to execute on our broader strategic objectives.

Pravin Dugel: Our current cash projections do not factor in the impact of clinical trial activities in NPDR and DME, as the scope of that program is dependent on FDA feedback. That said, And to be very clear, we do not currently intend to raise additional capital this year.

Speaker Change: Our current cash projections do not factor in.

Speaker Change: The impact of clinical trial activities and NPD R&D as.

Speaker Change: As the scope of that program is dependent on FDA feedback that said.

Speaker Change: To be very clear, we do not currently intend to raise additional capital this year.

Pravin Dugel: 2024 was a year of transformation for Ocular Therapeutix. and 2025 is shaping up to be even more impactful. What differentiates us is not just the speed and intensity, but also the precision and exceptionally high quality of our execution. In less than one year, we have built a world-class team, advanced a groundbreaking asset, and executed a registrational program that puts us in a position of strength as we move toward top-line data and a potential regulatory submission and approval.

Speaker Change: 2024 was a year of transformation for ocular therapeutics.

Speaker Change: In 2025 is shaping up to be even more impactful.

What differentiates us is not just the speed and intensity, but also the precision and exceptionally high quality of our execution.

Speaker Change: And less than one year, we have built a world class team advance a groundbreaking asset and executed a registrational program that puts us in a position of strength as we move towards top line data in.

Speaker Change: And a potential regulatory submission and approval.

Pravin Dugel: Today, we shared several updates designed to enhance and accelerate the Ex Pax League Registrational Program, further de-risking our path to approval. To summarize, First, the FDA approved an amendment to the Sol1 spa to incorporate redosing at weeks 52 and 76. increasing potential label flexibility to every 6 to 12 months.

Speaker Change: Today, we shared several updates designed to enhance and accelerate.

Speaker Change: <unk> Registrational program further derisking, our path to approval to.

Speaker Change: To summarize.

First the FDA approved an amendment to the sole one spot to incorporate re dosing at week 52 and 76.

Speaker Change: Increasing potential label flexibility to every six to 12 months.

Pravin Dugel: Second. due to the requirement to maintain masking until redosing at 52 weeks. We now expect top-line data for SOL1, including the 36-week primary endpoint, will be released in the first quarter of 2026. Sol1 Retention has been outstanding to date. and the vast majority of rescue treatments reviewed on a mass-based basis. have been in accordance with the pre-specified criteria of the protocol. Fourth, as a result of our updated SOL1 strategy for redosing, SOLAR has been streamlined, with the target randomization reduced from 825 to 555 subjects. This should accelerate the time to both solar data and regulatory filings for expaxly and wet AMD, all the while maintaining strong statistical powering of 90% based on our expectations of how expaxly will perform.

Speaker Change: Second.

Speaker Change: Due to their requirement to maintain masking until re dosing of 52 weeks. We now expect top line data for so one including the 36 week primary endpoint will be released in the first quarter of 2026 third.

Speaker Change: Third.

Speaker Change: So one retention has been outstanding to date.

Speaker Change: And the vast majority of rescue treatments, we viewed on a mass basis.

Speaker Change: I've been in accordance with the pre specified criteria of the protocol.

Speaker Change: Fourth as a result of our updated sole one strategy for re dosing.

Speaker Change: So Laura has been streamlined.

Speaker Change: With a target randomization reduced from 825 to 555 subjects.

Speaker Change: This should accelerate the time to both so large data.

Speaker Change: And regulatory filings for <unk> in wet AMD, all the while maintaining strong statistical powering of 90% based on our expectations of how <unk> will perform.

Pravin Dugel: Fifth. The non-inferiority margin for SOLAR is set at 4.5 letters. and Standard Rescue Criteria have been pre-specified to align with regulatory guidance. Enrollment has been excellent across both trials. SOL1 completed randomization ahead of schedule in December, and we previously announced SOLAR enrollment of 311 subjects across various stages of loading and randomization as of January 10th, 2025.

Speaker Change: Fifth.

Speaker Change: The non inferiority margin for so long is set at 4.5 letters.

Speaker Change: And standard rescue criteria have been pre specified to align with regulatory guidance.

Speaker Change: Six.

Speaker Change: Enrollment has been excellent across both trials.

Speaker Change: So one completed randomization ahead of schedule in December.

Speaker Change: And we previously announced so Laura enrollment of 311 subjects across various stages of loading and randomization as of January 10 2025.

Pravin Dugel: Seventh. EXPATSLEAF's opportunity extends beyond WET-AMD. And we expect FDA feedback on the clinical trial design for NPDR and DME in the first half of this year.

Speaker Change: Seven.

Speaker Change: Pax lease opportunity extends beyond wet AMD.

Speaker Change: We expect FDA feedback.

Speaker Change: On the clinical trial design for N P. D. R. <unk> in the first half of this year.

Pravin Dugel: And a. Ocular Therapeutix is well financed and has cash runway into 2028. We do not intend to finance this year. We're maintaining strong capital efficiency. as we advance toward key clinical readouts and a potential NDA submission in wet AMD.

Speaker Change: Okay.

Speaker Change: Ocular therapeutics is well financed and have cash runway into 2028.

Speaker Change: We do not intend to finance this year.

Speaker Change: We're maintaining strong capital efficiency.

Speaker Change: As we advance toward key clinical readouts, and a potential NDA submission and wet AMD.

Pravin Dugel: we are redefining the retina experience. Setting a New Standard in Treatment Durability, Flexibility, and Long-Term Outcomes. with strong execution, regulatory alignment. and Clinical Momentum.

We are redefining the retina experience.

Speaker Change: Setting a new standard treatment durability flexibility and long term outcomes.

Speaker Change: With strong execution.

Speaker Change: Regulatory alignment.

Speaker Change: And clinical momentum.

Pravin Dugel: We're well positioned to become a leading retina company.

Speaker Change: We are well positioned to become a leading retina company.

Pravin Dugel: Thank you for your time and continued support.

Speaker Change: Thank you for your time and continued support.

Operator: Operator. We are now ready to take questions. Thank you. As a reminder, if you'd like to ask a question, please press star 1 from your telephone keypad.

Speaker Change: Operator.

Speaker Change: We are now ready to take questions.

Speaker Change: Thank you.

Speaker Change: Wonder if you'd like to ask a question. Please press star one from your telephone keypad.

Tazeen Ahmad: Our first question comes from the line of Tazeen Ahmad with Bank of America. Please proceed with your question. Hi, guys. Good morning. Thanks for the update. A couple questions for me.

Speaker Change: Our first question comes from the line of cuisine Ahmad with Bank of America. Please proceed with your question.

Speaker Change: Hi, guys. Good morning, Thanks for the update.

Speaker Change: Couple of questions from me.

Pravin Dugel: Pravin, just given the stats that you provided about the continued strength of what you're seeing blinded in CELL1 in terms of patients staying in the study, as well as the redosing rates coming in, as you would have expected from your pre-specified criteria, can you give us a little bit more color about why you think it makes sense to make these changes, especially right now?

Speaker Change: Given the fact that you provided about the continued strength.

Speaker Change: We're seeing blinded and so one in terms of patients staying in.

Speaker Change: In the study as well as the re dosing rates coming in as you would've expected from a pre specified criteria can you give us a little bit more color about why you think it makes sense to make these changes, especially right now and then I can't recall.

Pravin Dugel: And then, secondly, in terms of making CELL-R a smaller study, just given the high demand that there has been, clearly, for patients to want to be in the study, can you talk about the reasons why it wouldn't make sense anymore to have a study of this size, just to add a little bit more cushion to the data set that we're expecting? And then I have one follow-up. Thank you. Thank you, Tazeen. Good morning to you, and again, thank you for your question.

Speaker Change: In terms of making cell or a smaller study just given the high demand that their hats, and clearly for a patient to want to be in the study can you talk about the reserves.

Speaker Change: Why it wouldn't make sense anymore to have a study of this size just to add a little bit more cushion.

Speaker Change: The data set that we're expecting and then I have one.

Speaker Change: Thanks.

Thank you Susie and good morning to you and again. Thank you for your question, what you've raised a really important point and let me try and give a comprehensive answer and I think this really speaks to the way we designed our solar programs.

Pravin Dugel: What you've raised is a really important point, and let me try and give a comprehensive answer. And I think this really speaks to the way we've designed our SOLE programs, and I include both. These are complementary trials, and I dare say that this is revolutionary and I think really quite historic. I think everyone in the world expected us to have SOL1 and SOL2, which really has been the tradition. In every, just about every trial that I know, it's been the same trial done twice. The second trial certainly is good to get the product approved and confirm the first trial.

Speaker Change: Glued both.

Speaker Change: These are complementary trials and I Dare say that this is revolutionary and I think really quite historic.

Speaker Change: I think everyone in the world expected us to have sold one and sold two which really has been the tradition and every just about every trial that I know it's been the same trial done twice.

Speaker Change: The second trial certainly is good to get the product approved and confirmed the first trial.

Pravin Dugel: But when you think about it, it's terribly inefficient because it really doesn't add any extra information whatsoever. Instead, what we've designed is two trials that are always to be taken together and are absolutely complementary in the information they provide. And this, I think, is a unique and, I dare say, a revolutionary and historic concept that will allow for efficiency both in terms of the logistics of the trials, the commercial applicability of the product, as well as the regulatory pathway. The bottom line in what we announced today, the bottom line is that we will potentially get expats to patients faster and with a better label.

Speaker Change: But when you think about it it's terribly inefficient because it really doesn't add any extra information whatsoever instead.

Speaker Change: Instead, what we've designed is two trials that are always to be taken together are absolutely complimentary and the information they provide and this I think is a unique and I dare say a revolutionary historic concept.

Speaker Change: That will allow for efficiency both in terms of the logistics of the trials the.

The commercial applicability of the product.

Speaker Change: As well as the regulatory pathway the bottom line and what we announced today.

Speaker Change: Online is that we will potentially get X pac's lead to patients faster.

Speaker Change: And with a better label.

Pravin Dugel: So let me go through the sequence of events. Two things happen. The first is that the FDA approved our re-dosing spa amendment for SOAR 1. at week 52 and 56. The second thing that happened is that we noted that the retention in SOAR 1 was absolutely superb. under Vasting, of course. So based on these two events, we're able to increase the efficiency of both studies. In SOAR 1, what we're able to do is to get information in the first year on the durability and flexibility of the drug, because now we have information at month 9, which is the primary endpoint that remains unchanged, and at month 12.

So let me go through the sequence of events.

Speaker Change: Things happened.

Speaker Change: The first is that the FDA approved our re dosing small amendment for sold one.

Speaker Change: At week 52 and 56.

Speaker Change: The second thing that happened is that we know that the retention.

Speaker Change: So one was absolutely superb.

Under basket of course, so based on these two events, we're able to increase the efficiency of both studies in.

Speaker Change: And so one what we're able to do is to get information on the first year on the durability and flexibility of the drug because now we have information at month nine which is the primary end point that remains unchanged and at month 12.

Pravin Dugel: And in the second year, with redosing, what we're able to do in SOAR 1 is to maximize the exposure of the drug to patients and satisfy many of the FDA's safety requirements. So immediately, SOAR-1 became a much more efficient clinical trial, and with that in mind, we're able to pass down that efficiency to SOAR-R, the way these trials were designed. So no longer did we need 825 patients in SOAR-R, we could maximize efficiency in terms of our resources as well as in terms of getting the filing to the FDA by reducing the size from 825 patients to 555 patients while maintaining the integrity of the statistics.

Speaker Change: And then the second year with re dosing, what we're able to do and so one is to maximize the exposure of the drug to patients and satisfying many of the Fda's safety requirements.

Speaker Change: So immediately so one became a much more efficient clinical trial.

Speaker Change: And with that in mind, we're able to pass down that efficiency to sell are the way. These trials were designed so no longer did we need 825 patients and so Laura we could maximize the efficiency in terms of our resources as well as in terms of getting the filing to the FDA by reducing the size.

Speaker Change: From 825 patients to 555 patients while maintaining the integrity of the statistics.

Pravin Dugel: The impact of this is that we will potentially have a much better label, a label that is a superiority label with flexibility of six months to 12 months. And the second impact, equally important of course, is that we will get to market potentially faster and more efficiently than we were able to before. So both of those things, terribly important in terms of the impact of what's happened today. What I want to note, very importantly also, is that the primary endpoint remains unchanged. Remember, the primary endpoint of SOL1 is at nine months. That remains unchanged. The statistics remain unchanged completely.

Speaker Change: The impact of this is that we will potentially have a much better label.

Speaker Change: Label that as a superiority label with flexibility of six months to 12 months and the second impact equally important of course is that we will get to market potentially faster and more efficiently.

Speaker Change: Then we were able to before so both of those things terribly important in terms of the impact of what's happened today.

Speaker Change: What I want to note.

Speaker Change: Very importantly, also is that the primary endpoint remains unchanged remember the primary endpoint of sold one is that nine months that remains unchanged. The statistics remain unchanged completely what we added today, what we announced today were completely added efficiency bonuses. These are.

Pravin Dugel: What we added today, what we announced today, were completely added efficiency bonuses. These are complementary trials designed to work together, and I believe they work together absolutely beautifully. Okay, that's super helpful.

Speaker Change: Our complimentary trials designed to work together and I believe they work together absolutely beautifully.

Speaker Change: Okay, that's super helpful.

Pravin Dugel: My one follow-up is that given that, as you said, the primary endpoint stays the same, can you give us a sense of what the FDA might be looking for from redosing now and so on? Well, again, the re-dosing allows for us in the first year to look to get information regarding flexibility and durability of the drug. Now we'll have information at month 9, again, that's the primary endpoint which remains absolutely unchanged, but additionally we'll also have information at month 12 regarding durability of the drug, so potentially there's flexibility in the label for month 9 as well as month 12.

Speaker Change: My one follow up is that given that as he said the primary endpoint stays the same but can you give us a sense of what the FDA might be looking for from re dosing now and for one.

Speaker Change: Well again, the re dosing allows for us in the first year to look to get information regarding flexibility and durability.

Speaker Change: The drug now will have information at month nine again, that's the primary endpoint, which remains absolutely unchanged, but Additionally, we will also happen formation at month 12 regarding the durability of the drugs that potentially there is flexibility in the label for month nine as well as months 12, and as I mentioned with the re dosing.

Pravin Dugel: And as I mentioned, with the re-dosing in the second year, there's more exposure of the drug to the patient, therefore we'll have even more data in regards to safety. The beauty of this is that when you think about the efficiency of SOAR 1, with a single injection in the first year, we'll have information for month 9 and month 12, and with repeat dosing for the second year, we'll have increased safety information with more exposure of the drug to patients. Okay, thank you for all the color. Thank you, everyone. Thank you.

Speaker Change: In the second year, there's more exposure of the drug to the patients. Therefore, we will have even more data in regards to safety.

Speaker Change: The beauty of this is that when you think about the efficiency of solar one with a single injection in the first year or will have information for a month nine month 12, and with repeat dosing for the second year will have increased safety information with more exposure of the drug to patients.

Speaker Change: Okay. Thank you for all the color.

Susan: Thank you Susan.

Biren Amin: Our next question is from the line of Biren Amin with Piper Sandler.

Speaker Change: Our next question is from the line of beer in almonds with Piper Sandler. Please proceed with your questions.

Biren Amin: Please proceed with your question. Yeah. Hi, guys. Thanks for taking my question, and congrats on all the updates.

Speaker Change: Yeah, Hi, guys. Thanks for taking my question and congrats on all the updates so maybe let me just start with so one what was the rationale for dosing.

Biren Amin: So, maybe, Pravin, let me just start with Sol 1. What was the rationale for dosing at week 76? I understand, you know, the week 52 dosing, but I was trying to understand, I guess, you know, the rationale for week 76. And then, you know, second question is, for Sol 1, will all patients receive redosing at week 52 and week 76, regardless of the arm, including the control arm? And also, will those patients with prior rescues receive redosing at weeks 52 and week 76?

Speaker Change: Week 76, I understand you know the week 52 dosing.

Speaker Change: But I was trying to understand I guess.

Speaker Change: Rationale for a week 76, and then second question is for Sul, One will all patients receive re dosing at week 52 weeks.

Speaker Change: Week to week 76, regardless of the arm.

Speaker Change: The control arm and also will those patients with higher rescues.

Speaker Change: Receive re dosing at week 52 and week 76.

Pravin Dugel: Very good morning, and thank you for your question. The answer for the first one is very simple. We wanted to maximize, again, the exposure of the drug to patients to satisfy the FDA safety requirements, thus redosing at week 52 and week 76, with the study ending at week 104. The answer to your second question, yes, every patient will be redosed at week 52 and at week 76. The redosing will occur with the same drug that the patient was randomized to, regardless of rescue. That's very important. The answer to your question is, yes, everybody will be redosed at week 52 and week 76 with the original drug that they were randomized to.

Speaker Change: Very good morning, and thank you for your question the answer for the first one is very simple we wanted to maximize again the exposure of the drug to patients to satisfy the U S.

Speaker Change: D a safety requirements with us.

Speaker Change: Re dosing at at week, 50, 652, I'm, sorry at week, two and week 76.

Speaker Change: With the study ending at week 100 for the answer to your second question, Yes every patient will be reduced.

Speaker Change: At week 52, and at week 76, the re dosing will will will occur with the same drug that the patient was randomized to regardless.

Speaker Change: Rescue and that's very important is the answer to your question is yes, everybody will be reduced.

Speaker Change: At week 52 at week 76, with the original drug that they were randomized to I hope that answers. Your question. Thank you Barry that dogs and I've got a follow up so on solar as a result of these changes you clearly.

Biren Amin: I hope that answers your question.

Biren Amin: Thank you, Biren. That does, and I've got a follow-up.

Biren Amin: So, on SOLAR, as a result of these changes, you clearly reduced the size to 555 patients. which I think, you know, it was that primarily due to the safety data that you're generating from Sol1 because I think now you would have another 172 patients that are redosed with Expaxly from Sol1. Whereas, I think you reduce the need for the patients to be re-dosed with Zolar by about 108 patients within the expected period. And Biren, again, thank you, you're exactly right. Your explanation is exactly correct. What we did was we designed SOLAR originally to have 825 patients to satisfy the FDA safety requirements.

Speaker Change: Reduce the size to 555 patients.

Speaker Change: Which I think.

Speaker Change: It was that primarily due to this the safety data that you're generating from saw one because I think now you would have another 172 patients that are re dose with <unk> Franco wide.

Speaker Change: Whereas I think you reduced.

Speaker Change: The need for the.

Speaker Change: Patients can be re dosed once all are by about 108 patients within the expensing more.

Speaker Change: And bear in again, thank you you're exactly right.

Speaker Change: Your explanation is exactly correct. What we did was we designed so our original eight two.

Speaker Change: 825 patients to satisfy.

Speaker Change: The FDA safety requirements.

Pravin Dugel: And with the redosing amendment that we were able to get from the FDA, we were able to satisfy the safety requirements with both studies combined with the ability to reduce the number of patients from 825 patients to 555 patients while still maintaining the statistical significance. So your answer to your question is exactly correct.

Speaker Change: And with the re dosing amendment that we were able to get from the FDA.

Speaker Change: We were we're able to satisfy the safety requirements with both studies are combined.

Speaker Change: With with the ability to reduce the number of patients from 825 patients to 555 patients while still maintaining the statistical significance. So.

Speaker Change: Your answer to your question is exactly correct. Thank you.

Biren Amin: Thank you. And then maybe one last question, I guess from a timeline standpoint, were these changes to SOL1 and SOLR underway or made when the board constructed your performance phase package on ocular share price hitting, you know, I think there were four different targets between $15 and $30, so I guess I want to understand if these changes provide increased confidence on hitting those performance targets. Yes. So, Biren, again, thank you very much for the question. The answer, and obviously we have discussions with the FDA that are ongoing, and we want to keep those discussions confidential.

Got it and then maybe one last question I guess from a timeline standpoint with these changes the sole one in Seoul are underway or made when the board constructed Europe performance based package on Oculus share price hitting I think there are four different targets between $15 $30. So I guess I want to understand if the change.

To provide increased confidence on hitting those pro forma targets.

Speaker Change: Yes, so beer and again, thank you very much for the question. The answer is obviously, we have discussions with the FDA that are that are ongoing and we want to keep those those those discussions confidential we don't discuss them publicly as with my discussions with the board, but suffice it to say that our confidence.

Pravin Dugel: We don't discuss them publicly, as with my discussions with the board. But suffice it to say that our confidence as a company in the success of these trials are higher than ever, and certainly my confidence particularly is higher than ever. And you'll see that everything in this company is aligned to make sure that we ensure the success of both trials.

Speaker Change: As a company in.

Speaker Change: And the success of these trials are higher than ever.

Speaker Change: And certainly my confidence.

Speaker Change: Particularly is higher than ever and that Youll see that everything in this in this company is aligned.

Speaker Change: To make sure that when sure the success of both trials.

Biren Amin: Thank you. Great.

Speaker Change: Thank you great. Thanks for taking my questions.

Biren Amin: Thanks for taking my question. Absolutely.

Speaker Change: Absolutely.

Colleen Kusy: The next questions are from the line of Colleen Kusy with Baird. Please proceed with your questions. Great. Thanks.

Speaker Change: The next questions are from the line of choline Goosey with Baird. Please proceed with your question.

Colleen Kusy: Good morning, and thanks for taking our questions. So, just to maybe clarify, for the redosing of patients in SOLE1, is that just for the FDA's safety requirement for redosing, or do you need to show anything for efficacy in that protocol in the second year? And then I have a follow-up.

Speaker Change: Great. Thanks, Good morning, and thanks for taking our questions. So for the REIT just to maybe clarify further re dosing of patients in Seoul. One is that just for the F. D. A safety requirement for re dosing or do you need to show anything for efficacy in that protocol in the second year, and then I have a column.

Pravin Dugel: Colleen, good morning, and thank you for your question. The answer is that it really is for the safety requirement for the FDA. However, what it does allow us to do, again, is get information given this, because remember, it's not just the matter of taking the second year separately, but also taking the second year in regard to how it affects the first year. So what it allows us to do is to get that extra information that we will now have, not only at month nine, but also at month 12. So it does allow for the flexibility that we hope to get in the label, because we have additional information now at month 12, as well as month nine.

Speaker Change: Colin Good morning, and thank you for your question. The answer is that it really is for the safety requirement for the FDA. However, what it does allow us to do again is good information given this because remember it's not just a matter of taking the second year separately, but also taking the second year in regard to how it affects the first year.

Speaker Change: So what it allows us to do is to get that extra information that we will now have not only at month nine but also at month 12. So.

Speaker Change: It does allow for the flexibility.

Speaker Change: But we hope to get in the label.

Speaker Change: Because we have additional information out month 12, as well as month nine but again, we will satisfy the safety requirements, but we will also gain additional information in the second year regarding re dosing. So this is not a requirement for hitting the primary end point I want to make that very very clear it is important to emphasize that.

Pravin Dugel: But again, we will satisfy the safety requirements, but we will also gain additional information in the second year regarding redosing. So this is not a requirement for hitting the primary endpoint. I want to make that very, very clear. It's important to emphasize that nothing about the original primary endpoint changes. The primary endpoint remains at month nine, and the statistics remain the same. This is added efficiency today. Got it. That's helpful. Thank you.

Speaker Change: Nothing about the original primary endpoint changes the primary endpoint remains at month nine and the statistics remain the same this is added efficiency today.

Speaker Change: Okay.

Speaker Change: Got it that's helpful. Thank you and then I know when you first shared the solar trial design last summer I think it was a 48 week endpoint and then but that was prior to talking to the FDA now you're talking about 56 week endpoint. So can you just talk about what drove that change and what that means for dosing schedule, which I believe exactly still coming at US every 24 weeks I'm just kind of talk about that 56 weekend likely.

Colleen Kusy: And then I know when you first shared the SOLAR trial design last summer, I think it was a 48-week endpoint, but that was prior to talking to the FDA. Now, you're talking about a 56-week endpoint. So can you just talk about what drove that change and what that means for your dosing schedule, which I believe X-FACTS is still going to be dosed every 24 weeks. So just kind of talk about that 56-week endpoint. Yeah. Thank you.

Speaker Change: Yeah.

Speaker Change: Yes. Thank you. Thank you Colin.

Pravin Dugel: Thank you, Colleen. So, you're exactly right. I think the first time you might have heard about the 48-week endpoint for SOLAR was in our June Investor Day. And I want to emphasize, if you go back and check your notes then, we made it absolutely clear that we were proposing the SOLAR clinical trial design at risk. And I think those two words, at risk, were quite a few times in that meeting. And the reason we did that is we made it very clear, very transparently, that we had not yet gone to the FDA for formal approval regarding this trial design.

Speaker Change: So youre exactly right I think the first time you might have heard about the 48 week endpoint for so long was in our June Investor Day, and I want to emphasize if you go back and check. Your notes then we made it absolutely clear that we were proposing that so Laura.

Speaker Change: Clinical trial design at risk and I think those two words at risks were mentioned quite a few times in that meeting and the reason we did that is we made it very clear very transparently that we had not yet gone to the FDA for formal approval regarding this trial design. So that's why it was at risk now we did subsequently.

Pravin Dugel: So, that's why it was at risk. Now, we did subsequently go to the FDA, and the FDA came back and told us that they preferred a primary endpoint at Week 52 or later. And as you know, we have a minimal amount of risk possible. In fact, we didn't want to take any risk as far as our regulatory pathway is concerned. So, then we decided, given their preference, to pick Week 56. And the FDA has now accepted, in writing, our proposal to pick the primary endpoint for SOLAR at Week 56. I hope that answers your question, Colleen.

Speaker Change: Go to the FDA and the FDA came back and told us that they preferred a primary endpoint at week 52, or later and as you know we have a history of doing everything per the FDA. We wanted to make sure that we did it with a minimal amount of risk possible. In fact, we would want to take any risk as far as our regulatory pathway is concerned.

Speaker Change: So then we decided given their preference to pick week 56, and the FDA has now accepted in writing our proposal to pick the primary endpoint for so long at week 56, So I hope that answers your question Colin.

Colleen Kusy: Great, thanks. And last one, just any timelines for solar recruitment now in light of the decrease in the studies? Yes, so Colleen, we did give an update at JPM, you know, as was said in my prepared statement. Since then, what I can tell you is that we've been thrilled with the recruitment of SOLAR, and we will give you an update when appropriate, but it may be a little bit too early at this point. But thank you for your question. Understood. Thanks for taking our questions. Thank you.

Colin: Great. Thanks, and last one just any timelines for solar recruitment now in light of the.

Speaker Change: The.

Speaker Change: The Christmas or the size.

Yeah. So Collin, we did give them an update at J P M.

Speaker Change: As was said in my prepared statements.

Speaker Change: Since then what I can tell you is that we've been thrilled with the recruitment.

Speaker Change: So long and we will give you an update when appropriate but it may be a little bit too early at this point, but thank you for your question.

Speaker Change: Understood. Thanks for taking my questions.

Speaker Change: <unk>.

Kelly Shee: The next question is from the line of Kelly Shee with Jeffries. Please proceed with your question.

Speaker Change: The next question is from the line of Kelly <unk> with Jefferies. Please proceed with your question.

Speaker Change: Yeah.

Clara: Hi, this is Clara. So you mentioned that you intend to submit an NDA after a 56-week primary analysis. We're also just trying to understand whether you would expect to have some long-term reducing durability data in the future.

Claire: Hi, This is Claire for Kelly, Thanks for taking our question and congrats on that.

Claire: So you mentioned that you intend to submit NDA after 55th suite primary endpoints.

Speaker Change: <unk> has reached so understand as a primary endpoints do not change.

Speaker Change: Trying to understand whether you would expect to have some long term re dosing durability data is so one at schwab by that time.

Pravin Dugel: as well by that time and also just want to clarify whether Clara, good morning, and thank you for your question. Very important questions, and I want to make it very clear as to what the FDA requirements are for NDA submission versus the information that we'll gather. To be very, very clear, what the FDA requires for the NDA submission is hitting the primary endpoint in both studies. So again, the primary endpoint for SOAR 1 at month 9 remains the same. The primary endpoint for SOLAR is at week 56, and our intention is that with presumably a positive study at week 56 with SOLAR, we will submit the NDA application to the FDA.

Speaker Change: And also just wanted to clarify whether the FDA requires Jeff portion of data to support the IV dosing flexibility portion on the label. Thank you.

Speaker Change: Good morning, and thank you for your question.

Speaker Change: Very important questions and I want to make it very clear as to what the FDA requirements are for four.

Speaker Change: For our NDA submission versus the information that we will gather to be very very clear of what the FDA requires for the NDA submission is hitting the primary endpoint in both studies. So again the primary endpoints for solely one at month nine remains the same.

Speaker Change: Primary endpoint for so long is at week 56, and our intention is that with the with presumably a positive study at week 56 with civil law, we will submit the NDA application to the FDA that is unchanged.

Pravin Dugel: That is unchanged. We just expect, given the announcements today, that SOLAR will be recruited with more efficiency given the fact that the sample size is smaller.

Speaker Change: Just expect given the announcements today, that's so large we will be recruited with more efficiency given the fact that the sample size is smaller now in regards to your other questions a.

Pravin Dugel: Now, in regards to your other questions... Regarding other requirements, yes, the FDA does have safety requirements, as you're aware. They will be fulfilled with the combination of patients in the second year in both SOL1 and SOLR. In addition to that, we will also have a significant amount of information that we believe we can leverage for commercial success, and some of which you've already talked about and we've already talked about, which is the redosing of this drug that is now available both in SOL1 and in SOLR. And remember, we also have a numeric analysis that we're able to do with the third arm in SOLR, which compares this drug to high-dose ILEA.

Speaker Change: Regarding other requirements, yes, the FDA does have safety requirements as you are aware the.

Speaker Change: They will be fulfilled with the combination of patients in the second year in both sold one and so Laura.

Speaker Change: In addition to that we will also have a significant amount of information.

Speaker Change: We believe we can leverage for commercial success, and some of which you've already talked about and we've already talked about which is the re dosing of this drug that is now available both in sold one and so lar and remember we also have a numeric analysis that we're able to do with the third arm is so large.

Speaker Change: Which compares this drug to high dose Eylea now that is not for statistical analysis, that's where numeric analysis, where you can imagine we will have between these two studies a significant amount of data that is not necessarily required by the FDA certainly is not required for approval of our NDA submission.

Pravin Dugel: Now, that is not for statistical analysis, that's for numeric analysis, but you can imagine we will have between these two studies a significant amount of data that is not necessarily required by the FDA. Certainly, it's not required for approval or NDA submission, but we can leverage for our commercial advantage, and we do intend to do that.

Speaker Change: But we can leverage for our commercial advantage and we do intend to do that thank you for your questions there.

Pravin Dugel: Thank you for your question, Clara.

Speaker Change: Thank you.

Sean McCutcheon: Our next question is from the line of Sean McCutcheon with Raymond James. Please proceed with your question. Hi, guys. Thanks for taking the question. So for SOAR, could you give some detail on, you know, what you think the FDA expectations are, what your expectations are for, you know, what would be an acceptable number of rescues and timing of rescues regardless of if you hit the non-inferior or land within the non-inferiority margin? Thanks.

Speaker Change: Our next question is from the line of Sean Mccutcheon with Raymond James. Please proceed with your questions.

Sean McCutcheon: Hi, guys. Thanks for taking the question.

Speaker Change:

Speaker Change: So for sole or could you give some detail on what you think the FDA expectations are what your expectations are for.

Speaker Change: What would be an acceptable number of rescues and timing of rescues regardless.

If you hit the non land within the non inferiority margin. Thanks.

Pravin Dugel: Sean, good morning and thank you for your question. Your question is a very important question, of course. So let me discuss rescues. We mentioned today, I just want to make clear, that the non-inferiority margin was 4.5 letters and I just want to emphasize that. That is because we're exactly in guidelines with the FDA. We've always done that and we expect to do that with everything that we do in regards to study design. In regards to the rescues, we have not detailed the rescue criteria as yet for competitive reasons, but we will do so. But here's what I can tell you.

Speaker Change: Sean Good morning, and thank you for your question. Your question is a very important question of course, so let me discuss rescues we mentioned today I just want to make clear that the non inferiority margin was four five letters and I just want to emphasize that that is because we're exactly in guidelines with the F. D. A.

<unk> always done that in weeks.

Speaker Change: We expect to do that with everything that we do in regards to study design.

Speaker Change: In regards to the rescue rescues we have not detailed the rescue criteria as yet for competitive reasons, but we will do so but here's what I can tell you.

Pravin Dugel: We will detail those when appropriate. You can expect the rescue criteria to be of no surprise. They will be absolutely in line with the traditional rescue criteria that you've seen in the past. The FDA has given very clear guidelines of what they think about rescues, not just for us, but for all studies. The FDA has clearly stated, and this was stated most recently by Dr. Boyd in the American Academy of Ophthalmology meeting, that the first rescue in a non-inferiority study will be allowed. as long as it doesn't affect the primary endpoint. And that is a period of approximately three months or so as a rule of thumb before the primary endpoint.

Speaker Change: We will we will detail those when appropriate.

Speaker Change: You can expect the rescue criteria to be of no surprise, there will be absolutely in line with the traditional rescue criteria that you've seen in the past.

Speaker Change: The FDA has given very clear guidelines of what they think about rescue is not just for us but for all studies.

Speaker Change: <unk> has clearly stated and this was stated most recently by the Doctor Boyd and the American Academy of Ophthalmology meeting.

Speaker Change: That the first rescue in a non inferiority study will be allowed.

Speaker Change: As long as it doesn't affect the primary endpoint and the primary and that is the period of approximately three months or so as a rule of thumb before the primary endpoint all other rescues will be subject to review and again, that's been stated for a number of years now that is no different than any other clinical trial.

Pravin Dugel: All other rescues will be subject to review. And again, that's been stated for a number of years now that is no different than any other clinical trial and that is a general statement that still stands. However, what I can tell you is that I believe we will have a huge advantage due to the design of our clinical trials. Remember, these are complementary clinical trials. And remember that SOLAR will never be reviewed by any regulatory agency without a positive SOL1 study. And when these rescues for SOLAR are being evaluated, it'll be evaluated in the context of a positive SOL1 study.

Speaker Change: And that as a general statement that still stands.

Speaker Change: However, what I can tell you is that I believe we will have a huge advantage.

Speaker Change: Due to the design of our clinical trials.

Speaker Change: Remember these are complementary clinical trials and remember that solar will never be reviewed by any regulatory agency without a positive. So one study.

Speaker Change: And when these rescues for so long are being evaluated it'll be evaluated in the context of a positive solo one study. So the regulatory agencies will have a very clear idea that this drug will last for nine to 12 months based on our positive sold one result, so.

Pravin Dugel: So the regulatory agencies will have a very clear idea that this drug will last for nine to 12 months based on a positive SOL1 result. So again, the rescues will be reviewed in context of a positive SOL1 study which will define the durability of this drug, which I will think will be very much to our advantage. Again, this also emphasizes the advantage that we have of having these two complementary studies.

Speaker Change: Again.

Speaker Change: The rescues will be will be reviewed in context of a positive. So one study, which will define the durability of this drug which I think will be very much towards vantage again. This also emphasizes the advantage that we have of having these two complementary studies. Thanks for your question Sean.

Pravin Dugel: Thanks for your question, Sean.

John Woolman: Thank you. Our next questions are from the line of John Woolman with Citizens JMP. Hey, thanks for taking the questions, Pravin. Two from us. Can you discuss the change in powering for solar now for the primary? And then stepping back, it seems like these changes have two big implications. One is the accelerated potential timing to a filing, but then also the new label information. But how do you think about the importance of those two? Because my expectation would be, if you get a year on the label, the docs could treat extended, they do anyway. So how much value is that 52 weeks in the label versus just getting to market quicker?

Speaker Change: Thank you.

Speaker Change: Our next questions are from the line of John woven with citizens JMP. Please proceed with your question.

Speaker Change: Hey, Thanks for taking the questions pertaining to from US can you discuss the change in powering for solar now for the primary.

Speaker Change: And then stepping back it seems like these changes are too big.

Speaker Change: Big implications one is the accelerated hydroponics.

Speaker Change: Turning to our filing but then also the new label information, but how do you think about the importance of those two because my expectation would be if you get a year on the label docs could treat and extend do anyway. So how much value is at 52 weeks in our label versus just getting to market quicker.

Speaker Change: Yeah.

Pravin Dugel: John, good morning, and thank you for your questions. Again, very important question. You know, look, as far as the solar powering is concerned, we haven't guided you to that publicly, but what I can tell you is nothing changes. You know, we had the 825 patient number to satisfy the FDA safety requirements. The powering and the statistics really do not change at all. We're able to reduce the size because of the redosing amendment that was approved by the FDA for SO1. The statistics remain very robust and unchanged for us.

John: Hi, John Good morning, and thank you for your questions again very important question.

John: Look as far as the sole or powering is concerned we haven't guided you do that publicly but what I can tell you is nothing changes.

John: We had the 825 patients patient number to satisfy the Fda's safety requirements.

John: The powering and the statistics really do not change at all were able to reduce the size because of the re dosing amendment that was approved by the FDA for solo one.

John: Statistics remain very robust and unchanged for us in regards to your second question regarding labeling.

Pravin Dugel: In regards to your second question regarding labeling, you know, look, you know, as a physician, I can tell you, as someone who has practiced for the last 30 years, that the label becomes very important for several reasons. You know, one is scientific. It gives you the scientific data of what this drug does, which would be very important to see. The opportunity is there in this study to find out the durability of this drug in a scientific manner, and that is very valuable information for physicians and for patients and for payers alike. The second reason for the labeling is really for the payers, and it will give us a huge commercial advantage.

John: As a physician I can tell you as someone who was practice for the last 30 years the label becomes very important for several reasons.

John: One is scientific it gives you the scientific data.

John: What this drug does which would be very important to see the opportunity is there in this study to find out the durability of this drug in a scientific manner.

John: And that is very valuable information for physicians and for patients and for payers alike.

John: And the reason for the labeling is really for for the payers.

John: It will give us a huge commercial advantage so.

Pravin Dugel: So, our goal strategically is to have the best label that the market has seen. A label that is the superiority label, which will be the first and only of its kind, potentially, and one with a great deal of flexibility of dosing from six months to 12 months. Thanks for your question, John.

John: Our our goal strategically is to have the best label that the market has seen a label that is the superiority label.

John: It will be the first and only of its kind potentially and one with a great deal of flexibility of dosing from six months to 12 months. Thanks for your question John.

John Woolman: Thanks, Kevin.

Speaker Change: Thanks, Brian.

Yi Chen: Our next questions are from the line of Yi Chen with H.E. Wainwright. Thank you for taking my question. With respect to the MPB or MBE. Once you get the FDA feedback on clinical trial design, how quickly do you anticipate to... those two indications. trials, and do you intend to advance both?

Speaker Change: Our next questions are from the line of <unk> Chen with H C. Wainwright. Please proceed with your questions.

Speaker Change: Thank you for taking my question with respect to the MTBE or M D.

Speaker Change: Once you get the Fda's feedback on clinical trial design, how quickly do you anticipate to have plans to those two indications in two clinical trials and do you intend to advance both indications concurrently thank you.

Pravin Dugel: Good morning. Again, thank you for your question. I'm glad you asked about NPDR and DME, and I'm glad that you put those together, because I think it's very important to emphasize that with the Helio study, we have shown absolutely everything to you, which is every single eye of every single patient. And what you'll see there is not only a remarkable result in nonproliferative diabetic retinopathy or NPDR, but also in diabetic macular edema or DME. In fact, every single patient who had diabetic macular edema on entry of that study improved. And what you saw in the angiogenesis meeting is a remarkable presentation by Dr. Ehlers, where he showed that very clearly that these patients with fluid improved significantly after a single injection after 48 weeks.

Speaker Change: Yeah. Good morning again, thank you for your question.

Speaker Change: I'm glad you asked about MP, Dr. Anne <unk>, and I'm glad that debt that you put those together because I think it's very important to emphasize that with the Helios study. We have shown absolutely everything to you which is every single I have every single patient and what Youll see there is not only a.

Speaker Change: A remarkable result in non proliferative diabetic retinopathy or PDR, but also in diabetic macular edema or <unk>. In fact every single patient who had diabetic macular edema on entry of that study improved and what you saw.

Speaker Change: In the angiogenesis.

Speaker Change: Meeting is a remarkable presentation by Dr hours, where he showed that very clearly that these patients with fluid improved significantly after a single injection. After 48 weeks and so our goal is to pursue notch not just N PDR, but also DMA.

Pravin Dugel: And so our goal is to pursue not just NPDR, but also DME. How the trial will be designed to you, we don't know yet, because we will still meet with the FDA formally. We committed to doing that in the first half of this calendar year. That has not changed. How quickly we will implement that depends on that meeting, so I can't say now. But what I can say and what we did say is that we are financed very, very efficiently. We are very disciplined in our financial expenditures. And our intent is to keep the projections the way they are, which is that we are financed into 2028.

Speaker Change: How the trial will be designed to you we don't know yet because we will.

Speaker Change: Still meet with the with the FDA, formerly with.

Speaker Change: We committed to doing that in the first half of this calendar year that has not changed how quickly we will implement that depends on that meeting. So I can't say now, but what I can say and what we did say is that we are financed very very efficiently. We are very disciplined.

Speaker Change: In our financial expenditures and our intent is to keep the projections. The way. They are which is that we are financed into 2028 and at this point, we do not have any intention of requiring any additional funding this year and that remains.

Pravin Dugel: And at this point, we do not have any intention of requiring any additional funding this year, Thank you for your questions.

Speaker Change: Thank you for your question.

Greg Harrison: Our next question is from the line of Greg Harrison with Scotiabank.

Speaker Change: Our next question's from the line of Greg Harrison with Scotiabank. Please proceed with your question.

Greg Harrison: Pleasure to see you. Hey, good morning. Thanks for taking the question.

Greg Harrison: Hey, good morning, and thanks for taking the question.

Pravin Dugel: I'm curious what your expectations are for the percentage of patients that could show durability to 52 weeks without rescue in Sol1, and to what extent do you think it could be used that way in practice? Greg, good morning, and thank you for your question. You know, the data, first of all, it's very, very valuable information. And we don't shy away from this at all, not only because it's very valuable, but we believe that we're going to win, quite honestly. We believe that there are a number of patients that will go to 52 weeks, and this is based on the U.S.

Greg Harrison: Curious what your expectations are for.

Greg Harrison: The percentage of patients that could showed durability to 52 weeks without rescue and sell one and to what extent do you think it could be used that way in practice.

Greg Harrison: Greg Good morning, and thank you for your questions.

Speaker Change: The data first of all it's very very valuable information and we don't shy away from this at all because not only because it's very valuable but we believe that we're gonna went quite honestly. We believe that there are a number of patients that will go to $2 52 weeks.

And this is based on the U S study in the U S study with 60% of patients that went that long.

Pravin Dugel: study. In the U.S. study, we had 60% of patients that went that long with a single injection, and that was in a non-enhanced patient population. As you know, in previous discussions, we've gone through how painstakingly and thoughtfully we have selected our patients in a bespoke manner for each study to de-risk the patient selection and de-risk the outcomes. And the 60% that I quote to you, it really is in a unselected, non-enriched patient population. So we're very confident of what we will show at week 12. Remember that there are drugs that are in the market now that are approved on label for a two week or so extension, you know, some going to four months with not very many patients that have actually crossed that threshold in their study.

Speaker Change: With a single injection and that wasn't a non enhanced patient population.

Speaker Change: As you know in previous discussions we have gone through how painstakingly and thoughtfully we have selected our patients in a bespoke manner for each study to derisk, the patient selection and Derisked the outcomes.

Speaker Change: And the 60% that I quote to you.

Speaker Change: Really is in a unselected non enriched patient population. So we're very confident of what we will show at week 12.

Speaker Change: Remember that there are drugs that are in the market now that are approved on label for <unk>.

Speaker Change: For a two week course, though extension some going to four months with not very many patients that are actually cross that threshold in their study.

Pravin Dugel: So from our point of view, we're going to provide very valuable information here to physicians, payers, and patients alike. And we have the opportunity to have the best in class label as well.

Speaker Change: So from our point of view, we're going to provide very valuable information here to physicians payers and patients alike.

Speaker Change: And we have the opportunity.

Speaker Change: To have the best in class label as well. Thank you Greg for the question.

Pravin Dugel: Thank you, Greg, for your question. Thank you.

Speaker Change: Okay.

Speaker Change: Thank you.

Operator: This concludes our question and answer session.

Speaker Change: This concludes our question and answer session I'll now turn the call back to Dr. Praveen Dougal for closing remarks.

Pravin Dugel: I'll now turn the call back to Dr. Pravin Dugel for closing remarks. Once again, I'd like to thank everyone for taking the time to join us on our call today. We look forward to updating you on our progress.

Speaker Change: Once again I'd like to thank everyone for taking the time to join us on our call today.

Speaker Change: We look forward to updating you on our progress and if you have any follow up questions. Please reach out to Bill Slattery, our vice President of Investor Relations.

William Slattery: And if you have any follow-up questions, please reach out to Bill Slattery, our Vice President of Investor Relations. Have a great day, everybody. Thank you.

Speaker Change: Have a great day everybody.

Speaker Change: Thank you.

Operator: This concludes today's conference. You may disconnect your lines at this time, and thank you for your...

Speaker Change: This concludes today's conference you may disconnect your lines at this time and thank you for your participation.