Q3 2023 EyePoint Pharmaceuticals Inc Earnings Call

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Yeah.

Good morning, My name is.

I'll be your conference.

Today at this time I would like to welcome everyone to the ice pharmaceuticals, great work in 2023 financials like corporate development and Paul.

A question and answer session to follow at the completion of the expansion.

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Good night.

In accordance with the company.

I would now like to turn the call over to George Ellison, Executive Vice President and Chief Financial Officer.

Pharmaceuticals. Please go ahead.

Thank you and thank you all for joining us on today's conference call to discuss <unk> Pharmaceuticals third quarter 2023 financial results and recent corporate developments with me today is Dr. Jay Duker, President and Chief Executive Officer, Jay will.

Begin with a review of recent corporate updates and discuss the ongoing phase II clinical trials for <unk> thousand 19 O. One I will close with commentary on the third quarter 2023 financial results and we will then open the call for your questions.

Earlier. This morning, we issued a press release detailing our financial results and recent operational developments a.

A copy of the release can be found in the investors tab on the corporate website www Dot <unk> pharma dot com.

Before we begin our formal comments I'll remind you that various remarks, we will make today constitute forward looking statements for the purposes of the Safe Harbor provisions under the private Securities Litigation Reform Act of 1095.

These include statements about our future expectations clinical developments and regulatory matters and timelines the potential success of our products and product candidates financial projections, and our plans and prospects.

Actual results may differ materially from those indicated by these forward looking statements as a result of various important factors, including those discussed in the risk factors section on our most recent annual report on Form 10-K, which is on file with the SEC and in other filings that we may make with the SEC in the future.

Any forward looking statements represent our views as of today only while we may elect to update these forward looking statements at some point in the future. We specifically disclaim any obligation to do so even if our views change.

Therefore, you should not rely on these forward looking statements as representing our views as of any date subsequent to today.

I'll now turn the call over to Dr. Jay Duker, President and Chief Executive Officer of <unk> Pharmaceuticals.

Thank you George.

Everyone and thank you for joining us to discuss <unk> continued execution towards our milestones as we work to bring first in class therapeutics and delivery technologies to patients suffering from serious retinal diseases.

In the third quarter, we both advanced and expanded our product pipeline with the announcement of positive mask safety data in our ongoing <unk> and <unk> phase II clinical trials for our lead product candidate <unk> hundred one which is the small molecule for Roland <unk> and our proprietary bio <unk>.

<unk> <unk> technology.

As well as the unveiling of a new preclinical program <unk> 301.

<unk> 301 delivers a promising tied to activator, which you approach a fib.

Formerly known as <unk> 900, $707 eight formulated in <unk> E to potentially improve outcomes in wet age related macular degeneration or wet AMD and diabetic eye disease.

It's an exciting time at <unk> as our <unk> hundred one clinical trials approach key data events with top line phase two <unk> trial results anticipated in early December and Pavia results in Q2 of next year.

And as we plan to initiate a third phase II trial in diabetic macular edema or <unk> in Q1 of 2024.

I'll now review, our recent programming corporate updates and give an overview of upcoming catalysts.

Turning to our lead program <unk> 90 to one is being advanced as a potentially paradigm shifting treatment for patients suffering from <unk> mediated retinal diseases.

19, one is delivered with a single <unk> injection in the physician's office similar to the current FDA approved anti VEGF biologic treatments.

Lee Wei: Good morning, my name is Lee Wei and I will be your conference author later today. At this time, I would like to welcome everyone to the EyePoint Pharmaceuticals, the record is 2023, financial flows of recent corporate development conference calls. There will be a question and answer session to follow at the completion of those very remarks.

Unknown Executive: This is the advice of this college being recorded at the company's best.

19, you don't want is immediately bio available featuring an initial burst of drug followed by near constant zero order kinetic released for approximately nine months.

It might be 90 to one delivers for rolling up a selective and patent protected tyrosine kinase inhibitor formulated in a solid insert using our proprietary sustained release bio erodible <unk> technology.

George Elston: I would not like to turn the call over to George Elston, Executive Vice President and Chief Financial Auditor of the EyePoint Pharmaceuticals, Michael, please go ahead. Thank you, and thank you all for joining us on today's conference call to discuss EyePoint Pharmaceuticals third quarter 2023 financial results and recent corporate development. With me today is Dr. Jay Duker, President and Chief Executive Officer. Jay will begin with a review of recent corporate updates and discuss the ongoing phase two clinical trials for EYP 1901.

We're rolling it brings a new mechanistic approach to the treatment of VEGF mediated retinal diseases by acting as a pan VEGF receptor blocker blocking all bet, Jeff isoforms, we expect <unk> dollars 19, and one with its new MLA and sustained drug delivery for up to nine months to meaningfully reduce.

Treatment burden and the majority of wet AMD patients, while keeping vision and retinal anatomy stable.

George Elston: I will close with commentary on the third quarter 2023 financial results, and we will then open the call for your question. Earlier this morning, we issued a press release detailing our financial results and recent operational development. A copy of the release can be found in the Investors tab on the corporate website, www.ipointfarma.com.

We're rolling it features reduced off target binding.

And at clinically relevant doses does not inhibit tied to a critical pathway associated with vascular stability, which may result in an improved efficacy.

In a rodent model of retinal detachment Rowan have demonstrated neuro protection and because it blocks PDGF may also have anti fibrotic benefits.

George Elston: Before we begin our formal comments, I'll remind you that various remarks we will make today constitute forward-looking statements for the purposes of the safe harbor provisions under the Private Security's litigation reform act of 1995. These include statements about our future expectations, clinical developments and regulatory matters and timelines, the potential success of our products and product candidates, financial projections and our plans and prospects. Actual results made different materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in the risk factors section on our most recent annual report on form 10K, which is on file with the SEC and in other filings that we may make with the SEC in the future.

We were pleased to present preclinical and clinical data at multiple medical meetings that underscore the promising profile of <unk> 19 of one.

One highlight was that last month's retina Society meeting, where a comparison of the anti Angiogenic profile of three Teekay is we're rolling it exit to nib and Sunitinib validated <unk> as a pan VEGF receptor inhibitor that effectively blocks the critical pathways of pathologic angiogenesis.

Importantly, the data showed that for rolling it is differentiated from the other TK ice tested at retinal disease.

Unlike sunitinib <unk> does not bind the melanin.

George Elston: Any forward-looking statements represent our views as of today only. While we may elect to update these forward-looking statements at some point in the future, we specifically disclaim any obligation to do so, even if our views change. Therefore, you should not rely on these forward-looking statements as representing our views as of any date subsequent to today.

Unlike exit the nib for Roland is not expected to have a physiologic impact on normal tie to function.

As a reminder, the fully enrolled <unk> trial is evaluating <unk> 19 O. One in 160 subjects with previously treated wet AMD as a maintenance therapy with a goal to maintain stable vision and retinal anatomy for the majority of wet AMD patients for six months or longer following a single injection of <unk> hundred one.

Jay Duker: I'll now turn the call over to Dr. J. Dukeer, President and Chief Executive Officer of I Point Pharmaceuticals. Thank you, George.

This could represent a significant improvement compared to the current anti VEGF treatments that are dosed on average every two months in the United States under treat and extend protocol.

Jay Duker: Good morning, everyone, and thank you for joining us to discuss I Point's continued execution toward our milestones as we work to bring first-in-class therapeutics and delivery technologies to patients suffering from serious retinal diseases. In the third quarter, we both advanced and expanded our product pipeline with the announcement of positive mass safety data in our ongoing W-2 in Pavia phase-2 clinical trials for our lead product candidate, EYP-1901, which is the small molecule verolinib and our proprietary biorodable DERSERT-E technology.

This lifetime of frequent treatment represents a tremendous burden for patients physicians and the health care system in general.

He might be 19, no one has the potential to change this treatment paradigm into a treat to maintain model by providing sustained delivery of enrollment and for approximately nine months following induction treatment with a large molecule antibody, Jeff like Anne Walker.

This may allow patients and practitioners the flexibility to reduce the number of visits without sacrificing visual outcomes.

Jay Duker: As well as the unveiling of a new pre-clinical program, EYP-20301. EYP-20301 delivers a promising tie-to activator, resu-prote-to-fib, formerly known as AKB-977-8, formulated and derestured E to potentially improve outcomes in wet, age-related macular degeneration or wet AMD, and diabetic eye disease. It's an exciting time at EyePoint as our EYP-1901 clinical trials approach key data events with top-line phase 2-WO2 trial results anticipated in early December and pavilla results in Q2 of next year. And as we plan to initiate a third phase 2 trial in diabetic macular edema or DME in Q1 of 2024.

The subjects in the <unk> two trial randomized to two treatment arms, approximately two milligrams or approximately three milligrams of <unk> thousand 19, one or on label a flipper sept as a control.

All subjects in the trial received three loading doses of a flipper set on day, one month, one and month to followed by dosing of <unk> 19 to one or a sham injection 30 minutes after the last loading dose.

The FDA approval pathway for this program and the primary endpoint for <unk> is non inferiority in the change of best corrected visual acuity or be CPA for each of the $19 one arms versus the flipper set control arm.

The lower limit of non inferiority margin is defined as minus four five letter loss by the FDA.

For perspective patients do not generally notice a change in vision until they lose five or more letters, which is the equivalent of one line on an eye chart.

Jay Duker: I'll now review our recent program and corporate updates and give an overview of upcoming catalysts. Turning to our advanced as a potentially paradigm-shifting treatment for patients suffering from VEDGF-mediated retinal diseases. EYP-1901 is delivered with a single, interventional injection in the physician's office, similar to the current FDA-approved anti-VEDGF biologic treatments. EYP-1901 is immediately bio-available, featuring an initial burst of drug, followed by near constant zero-order kinetic release for approximately nine months. EYP-1901 delivers verolinum, a selective and patent-protected tyrosine-kindness inhibitor, formulated in a solid insert using our proprietary sustained release biodeurotable DuraSert e-technology.

I'd like to share our perspective in terms of targeted outcomes for the non inferiority be CBA as there are both numerical and statistical considerations for this outcome.

First a very successful outcome in <unk> would be to mirror. The phase <unk> results that showed an average of two five letter loss six months after <unk> 91, which is good.

Recall that <unk> was an all comers open label non randomized phase one trial.

Our learnings from that phase one trial, we modified inclusion and exclusion criteria for the <unk> trial in an effort to exclude is that were not responding to standard of care therapy.

We presented mast patient demographic data last quarter that reflects the fact that we enrolled a more controlled patient population in <unk> and in the phase one trial.

Jay Duker: Verolinum brings a new mechanistic approach to the treatment of VEDGF-mediated retinal diseases by acting as a pan-VEDGF receptor blocker, blocking all VEDGF-iceiforms. We expect EYP-1901 with its new MOA and sustained drug delivery for up to nine months to meaningfully reduce treatment burden in the majority of wedding of patients while keeping vision and retinal anatomy stable. Verolinum features reduced off-target binding, and at clinically relevant doses does not inhibit ty-2, a critical pathway associated with vascular stability, which may result in an improved efficacy.

Generally and outcome of minus three letters or better would be a very strong numerical outcome and possibly statistically non inferior even in this relatively small trial.

If the <unk> 19 to one arms match or better the minus one four letters difference versus the two milligram a flipper sub control, which was what was seen in the 16 week eight milligram eylea arm in the Pulsar trial. This would represent an outstanding outcome from a single injection of <unk>.

John.

Jay Duker: In a rodent model of retinal detachment, verolinum demonstrated neuroprotection, and because it locks PDGF may also have anti-fibrodic benefits. We were pleased to present preclinical and clinical data at multiple medical meetings that underscore the promising profile of EYP-1901. One highlight was that last month's retina society meeting where a comparison of the anti-antigenic profile of three TKI's, verolinum, exotinib, and pseudonymib validated verolinum as a pan-VEDGF receptor inhibitor that effectively blocks the critical pathways of pathologic angiogenesis.

In addition to stable BCA. It is critical that the <unk> 19, one continues to show a favorable safety profile consistent with the interim mass safety update through October one 2023 across all of the <unk> hundred one clinical trials.

As of October 1st approximately 170 patients have received <unk> hundred one with a minimum of four months follow up post injection from the ongoing phase II and <unk> two clinical trials and the completed <unk> phase one trial with no reported drug related ocular Sce's and no reported drug related to <unk>.

Sce's. This continues to give us confidence in the results of this crucial endpoint.

Jay Duker: Importantly, the data showed that verolinum is differentiated from the other TKI's tested retinal disease. Unlike synitinib, verolinum does not bind to melanin, and unlike exotinib, verolinum is not expected to have a physiologic impact on normal ty-2 function. As a reminder, the fully enrolled WO2 trial was evaluating EYP-1901 and 160 subjects with previously treated wet AMD as a maintenance therapy, with a goal to maintain stable vision and retinal anatomy for the majority of wet AMD patients for six months or longer following a single injection of EYP-1901.

The change in best corrected visual acuity is the primary endpoint reduction in treatment burden will also be a critical secondary outcome to consider given the unmet need in this patient population for more durable therapies.

For a clinically meaningful outcome, we believe that one or both <unk> 90 to one arms need to result in a reduction in treatment burden of a minimum of 50% or better for the six months following <unk> injection at week eight.

In addition, we also believe that 50% or greater of the <unk> 19, when treated eyes should be supplement free up to the week 32 visit along with a relatively stable anatomy as measured by OTT.

Jay Duker: This could represent a significant improvement compared to the current anti-venget treatments that are dozed on average every two months in the United States under a treatment extend protocol. This lifetime of frequent treatment represents a tremendous burden for patients, physicians, and the healthcare system in general. EYP-1901 has the potential to change this treatment paradigm into a treat to maintain model by providing sustained delivery of rural and for approximately nine months, following induction treatment with a large molecule anti-venget like and walker.

Based on our market research and KOL interactions. These endpoints will be meaningful to retina specialists, who treat wet AMD patients with.

We plan to host a virtual call with renowned retinal specialists, Dr. David Boyer and Dr. David loudly on November 9th at eight a M. Eastern time to discuss their perspectives on the current treatment landscape and the <unk> outcome considerations that I just reviewed.

Jay Duker: This may allow patients and practitioners the flexibility to reduce the number of visits without sacrificing visual outcomes. The subjects in the W2 trial were randomized to two treatment arms, approximately two milligrams, or approximately three milligrams, of EYP-1901, or unlabeled a flipper set as a control. All subjects of the trial receive three loading doses of a flipper set on day one, month one, and month two followed by dosing of EYP-1901 or a sham injection 30 minutes after the last loading dose.

We hope that you will all join US for this informative presentation and Q&A and you can find the link to that call in the investor tab of our website.

Looking ahead to the potential phase III pivotal trials for <unk> hundred one as maintenance therapy in wet AMD. Our current plan is to initiate the first trial by the fourth quarter of 2024.

This initial trial will be largely in the U S and Canada, we hope to initiate a second pivotal trial. Several months later, the second phase III trial will be largely outside of the U S.

Jay Duker: The FDA approval pathway for this program and the primary endpoint for W2 is non-inferiority in the change of best corrected visual acuity or BCVA for each of the 1901 arms versus the flipper set control arm. The lower limit of non-inferiority margin is defined as minus 4.5 letter loss by the FDA. For perspective, patients do not generally notice a change in vision until they lose five or more letters, which is the equivalent of one line on an eye chart.

The phase III <unk> trial of <unk> 91 was designed to mirror the anticipated design of the phase III trials based on our type C meeting with the FDA and other interactions with the agency.

The key differences are that the phase III trials will feature re dosing of <unk> 19 to one every six months and the primary efficacy endpoint will be non inferior change in visual acuity to approximately one year instead of eight months as it is in <unk>.

Jay Duker: I'd like to share our perspective in terms of targeted outcomes for the non-inferiority BCVA as there are both numerical and statistical considerations for this outcome. First, a very successful outcome in W2 would be to mirror the Phase 1 WO BCVA results that showed an average of 2.5 letter loss six months after EYP-1901 was injected. Recall that WO was an all-comers open label non-randomized Phase 1 trial. Based on learnings from that Phase 1 trial, we modified inclusion and exclusion criteria for the WO2 trial.

We expect to share more details about this trial in the coming months.

Now, let me turn to our second indication and PDR in June we reported that enrollment of the phase II via clinical trial was complete.

<unk> is a randomized controlled phase two trial evaluating <unk> as a potential nine months treatment for moderate to severe <unk>.

Similar to the <unk> two trial are Pavia trial saw significant investigator and patient interest during enrollment.

<unk> enrolled 77 patients exceeding the 60 patient target.

<unk>, who were randomly assigned to one of two doses of <unk> 19 to one approximately two milligrams for approximately three milligrams or to the control group that received a sham injection.

Jay Duker: In an effort to exclude eyes that were not responding to standard of care therapy, we presented massed patient demographic data last quarter that reflects the fact that we enrolled a more controlled patient population in WO2 than in the Phase 1 trial. Generally, an outcome of minus 3 letters or better would be a very strong numerical outcome and possibly statistically non-inferior, even in this relatively small trial. If the EYP-1901 arms match or better, the minus 1.4 letters difference versus the 2 milligram of flibrecept control, which was what was seen in the 16-week 8 milligram ILEA arm and the Pulsar trial, this would represent an outstanding outcome from a single injection of EYP-1901.

As in the wet AMD trials, you might be 19, no. One is delivered with a single <unk> injection in the physician's office.

As a reminder, and <unk> is a very common retinal disease that affects almost one third of diabetic adults over the age of 40 and its projected to impact over 14 million Americans by 2050.

In PDR blood vessels are weakened potentially leading to swelling of the macula, which is called diabetic macular edema or <unk> and may eventually resulted in abnormal blood vessel growth, which is called proliferative diabetic retinopathy or PDR.

Both DMA in PDR could ultimately result in severe visual loss is important to note that there remains a great unmet need for a safe efficacious at convenient treatment for NPD art that proactively reduces the risk of progressing to a sight threatening complication over the long term.

Jay Duker: In addition to stable BCVA, it is critical that the EYP-1901 continues to show a favorable safety profile, consistent with the interim mass safety update through October 1st, 2023, across all of the EYP-1901 clinical trial. As of October 1st, approximately 170 patients have received DYP-1901 with a minimum of four months follow-up post-injection, from the ongoing phase 2 pvf and WO2 clinical trials, and the completed WOF1 trial with no reported drug-related ocula SAEs and no reported drug-related systemic SAEs.

Approximately 90% of patients with MTR currently received no course of therapy apart from observation by their doctor until their disease progresses to dnb and or PDR.

Might be 19 in one in our phase II <unk> trial could potentially reduce the risk of progressing to these complications with a less intrusive treatment protocol.

Recently, we reported an interim analysis of mass safety data from the phase II <unk> clinical trial in NPR, which showed that as of October one 2023, <unk> 91 was well tolerated with no reported drug related ocular or drug related systemic sce's, demonstrating <unk> 19 <unk>.

Jay Duker: This continues to give us confidence in the results of this crucial endpoint. Although change-invest corrected visual acuity is the primary endpoint, reduction in treatment burden will also be a critical secondary outcome to consider, giving the unmet need in this patient population for more durable therapies. For a clinically meaningful outcome, we believe that one or both EYP-1901 arms need to result in a reduction in treatment burden of a minimum of 50% or better for the six months following EYP-1901 injection at week 8. In addition, we also believe that 50% or greater of the EYP-1901 treatment eyes should be supplement-free up to the week 32 visit, along with a relatively stable anatomy as measured by OCT.

Excellent safety profile at NPD are for the first time.

Top line data from the Pavia trial remains on track for the second quarter of 2024.

As mentioned earlier, we plan to initiate a phase II trial evaluating <unk> in Dnb and the first quarter of 2020 for which we are calling the Verona trial.

We will share details of that trial at a future date with Golar. The Verona trial is to gain experience with <unk> 19 in one in this potentially large indication.

In September we disclosed a new preclinical program called <unk> 301.

Jay Duker: Based on our market research and KOL interactions, these endpoints will be meaningful to retinus specialists who treat wet AMD patients.

<unk> 301 is tied to agonists RASM prototype, formerly known as <unk> $977, eight, which we have formulated to work into research E.

Jay Duker: We plan to host a virtual call with renowned retinal specialist Dr. David Boyer and Dr. David Lally on November 9 at 8 a.m. Eastern time to discuss their perspectives on the current treatment landscape and the WO2 outcome considerations that I just reviewed. We hope that you will all join us for this informative presentation in Q&A, and you can find the link to that call in the investor tab of our website.

This has the potential to provide interim vitriol sustained delivery over six months or longer to improve the treatment of wet AMD and diabetic eye disease pre.

Previous preclinical and clinical studies show that rasp prototypes delivered subcutaneously demonstrated proof of concept in diabetic eye disease, and we believe that delivering <unk> 23, a one <unk> has the potential to offer new site saving treatment for patients with severe retinal disease either.

Jay Duker: Looking ahead to the potential Phase III Pivotal Trials for EYP-1901 as maintenance therapy in wet AMD, our current plan is to initiate the first trial by the fourth quarter of 2024. This initial trial will be largely in the U.S, and Canada. We hope to initiate a second Pivotal trial several months later. This second Phase III trial will be largely outside of the U.S.

Loan or in combination with antibody chefs.

Finally, we were delighted to announce that <unk> expanded its board of directors with the appointment of Stewart duty, a seasoned biopharmaceutical financial executive who brings more than 25 years of experience to the role. We also strengthened our executive leadership team with the promotion of our CFO George Elsdon to the additional role.

Jay Duker: The Phase II WO2 trial of EYP-1901 was designed to mirror the anticipated design of the Phase III trials based on our type C meeting with the FDA and other interactions with the agency. The key differences are that the Phase III trials will feature redosing of EYP-1901 every six months, and the primary efficacy endpoint will be non-inferior change in visual acuity to approximately one year instead of eight months as it is in WO2.

Executive Vice President.

George his wealth of experience financial acumen, and strategic guidance, it's been a tremendous asset to our <unk> team.

Behalf of the entire leadership team, we welcome Stuart and congratulate George and we are grateful for their valuable leadership at <unk> point as we continue to build value for our shareholders. During this active time in the company's growth.

Jay Duker: We expect to share more details about this trial in the coming months.

Jay Duker: Now, let me turn to our second indication, NPDR. In June, we reported that enrollment of the Phase II Pivotal Clinical Trial was complete. The VA is a randomized controlled Phase II trial evaluating EYP-1901 as a potential nine-month treatment for moderate to severe NPDR. Similar to the WO2 trial, our Bavia Trial saw significant investigator and patient interest during enrollment. The trial enrolled 77 patients exceeding the 60 patient target. Patients were randomly assigned to one of two doses of EYP-1901, approximately two milligrams, or approximately three milligrams, or to the control group that received a sham injection. As in the Wed AMD trials, YP1901 is delivered with a single interpreter injection in the physician's office.

I'd like to thank the entire <unk> team for an incredibly productive quarter and I will now turn the call over to George to review the financials George.

Thank you Jay as the financial results for the three months ended September 32023 were included in the press release.

Issued this morning, my comments today will be focused on.

On a high level review for the quarter.

For the third quarter ended September 32023, total net revenue was $15 2 million compared to $10 million for the quarter ended September 32022.

Net product revenue for the third quarter was <unk> 8 million compared to net product revenues for the third quarter ended September 32022 of $9 7 million.

Jay Duker: As a reminder, NPDR is a very common retinal disease that affects almost one third of diabetic adults over the age of 40, and it's projected to impact over 14 million Americans by 2050. The Diabinolo blood vessel growth, which is called proliferative diabetic retinopathy, or PDR. Both DMA and PDR could ultimately result in severe visual loss.

Consistent with the exit from the commercial business. The decline in revenue resulted from the sale of boutique franchise in May 2023, along with the discontinuation of marketing activity for the <unk> franchise. This year due to the loss of pass through reimbursement by CMS effective one $1 23.

Net revenue from royalties and collaborations for the third quarter ended September 32023 totaled $14 4 million compared to $3 million in the corresponding period in 2022.

Jay Duker: It's important to note that there remains a great unmet need for a safe, efficacious and convenient treatment for NPDR that proactively reduces the risk of progressing to a site-threatening complication over the long term. Approximately 90% of patients with NPDR currently receive no course of therapy, apart from observation by their eye doctor, until their disease progresses to DME and or PDR. EYP1901 in our Phase 2 PDR could potentially reduce the risk of progressing to these complications, with a less intrusive treatment protocol.

The increase was primarily due to a recognition of deferred revenue from the sale of Utica, which will be recognized over a two year period, which began in Q2 of this year.

Operating expenses for the third quarter ended September 32023 totaled $29 6 million versus $28 4 million in the prior year period.

This increase was primarily driven by higher R&D spending on <unk> hundred one clinical trials, partially offset by lower sales and marketing expense.

Nonoperating expense net totaled $1 8 million and net loss was $12 6 million or <unk> 33 per share compared to a net loss of $18 4 million or <unk> 49 per share in the prior year period.

Jay Duker: Recently, we reported an interim analysis of mass safety data from the Phase 2 PDR clinical trial in NPDR, which showed that as of October 1st, 2023, EYP1901 was well tolerated with no reported drug-related ocular or drug-related systemic SAEs. Demonstrating EYP1901's excellent safety profile in NPDR for the first time.

Cash and investments at September 32023 totaled $136 million compared to $144 6 million at December 31, 2022.

We expect the cash cash equivalents and investments on September 32023 will enable us to fund our current and planned operations into 2025.

Jay Duker: Top-line data from the PVA trial remains on track for the second quarter of 2024.

Jay Duker: As mentioned earlier, we plan to initiate a Phase 2 trial evaluating EYP1901 and DME in the first quarter of 2024, which we are calling the Verona trial. We will share details of that trial at a future date. The goal of the Verona trial is to gain experience with EYP1901 in this potentially large indication.

In conclusion, we are pleased with <unk> progress in the third quarter and year to date and are well capitalized to advance our product pipeline to key value inflection points I will now turn the call back over to Jay for closing remarks.

Thank you George.

We believe <unk> as a potentially paradigm shifting treatment for patients suffering from serious retinal diseases, providing unique benefits that may include delivery of a rolling up consistently over approximately nine months.

Jay Duker: In September, we disclosed a new preclinical program called EYP20301. EYP20301 is tied to Agnes, Raza Protofib, formerly known as AKB978, which we have formulated to work endure a cert E. This has the potential to provide intra-vitriol-sustained delivery over six months or longer to improve the treatment of Wedding and Diabetic Eye Disease. Previous preclinical and clinical studies show that Raza Protofib delivered subcutaneously, demonstrated proof of concept in Diabetic Eye Disease, and we believe that delivering EYP20301 intra-vitrially has the potential to offer new psych-saving treatment for patients with severe retinal disease.

New mechanism of action to treat retinal disease beyond anti VEGF like an blockade.

The potential for neuro protection, and anti fibrosis, and a proven delivery technology with a positive safety profile.

I will close by recapping key upcoming catalysts, including top line data from our phase III <unk> clinical trial anticipated in early December.

The dosing of the first patient in the phase III <unk> clinical trial of <unk> hundred one in <unk> in the first quarter of next year and top line data release from our phase III <unk> clinical trial in the second quarter of 2024.

Jay Duker: Finally, we were delighted to announce that eyepoint expanded its board of directors with the appointment of Stewart-Duty, a seasoned biopharmaceutical financial executive who brings more than 25 years of experience to the role. We also strengthen our executive leadership team with a promotion of our CFO, George Elston, to the additional role of executive vice president. George's wealth of experience, financial acumen, and strategic guidance has been a tremendous asset to our eye point team.

This remains an incredibly exciting time for <unk> as we are well positioned to execute on our upcoming milestones and continue to transform the treatment landscape with innovative long term solutions to improve both the vision and the lives of patients with serious retinal diseases.

Thank you all very much for listening. This morning, I will now turn it over to the operator for questions.

Our first question comes from the line.

Jay Duker: On behalf of the entire leadership team, we welcome Stewart and congratulate George, and we are grateful for their valuable leadership at eye point as we continue to build value for our shareholders during this active time in the company's growth.

Your line is now open.

Good morning, Congrats on the progress thanks, very much for the call I have a couple of questions for you.

First one is.

I appreciate the transparency you guys have been with respect to your CPA outcome scenario ranges for the W. Two trial ahead of the data, but we've constructed in accordance with Kols and can you elaborate on what the Kols feedback have been regarding what they need to see from a trial, perhaps a preview of sorts of the upcoming Kols event and then.

George Elston: I'd like to thank the entire eye point team for an incredibly productive quarter, and I will now turn the call over to George.

George Elston: George to review the financials, George. Thank you, Jay. As the financial results for the three months ended September 30th, 2023 were included in the press release. Issued this morning, my comments today will be focused on a high level review for the quarter. For the third quarter ended September 30, 2023 total net revenue was 15.2 million compared to 10 million for the quarter ended September 30, 2022.

The second question is.

Upon positive data can you talk about how quickly you would be able to start the phase III program and is it possible to get the topline data in an accelerated fashion or should we think of it being a more traditional wet AMD phase III program timeline.

Thanks, Tyler I appreciate the questions and your interest.

George Elston: Net product revenue for the third quarter was 0.8 million compared to net product revenues for the third quarter ended September 30, 2022 of 9.7 million. Consistent with the exit from the commercial business, the decline in revenue resulted from the sale of the UT franchise in May 2023, along with the discontinuation of marketing activity for the DEXICU franchise this year due to the loss of pass through reimbursement by CMS effective 1123. Net revenue from royalties and collaborations for the third quarter ended September 30, 2023 total 14.4 million compared to 0.3 million in the corresponding period in 2022.

First of all with respect to the BCA ranges.

So there's really kind of three ways to look at this and the first way is what does the FDA want.

And Thats pretty clear.

The non inferiority margins got to be minus $4 five letters you can't cross it with your confidence intervals.

And depending on your any of your study in your standard deviation you could come pretty close to $4 five and get a result, but the second part of what you asked is what does it what does the kols want.

And interestingly when you ask them and Im sure you have.

George Elston: The increase was primarily due to a recognition of deferred revenue from the sale of UTIC which will be recognized over a two year period which began in Q2 of this year. Operating expenses for the third quarter ended September 30, 2023 total 29.6 million versus 28.4 million in the prior year period. This increase was primarily driven by higher R&D spending on EYP 1901 clinical trials partially offset by lower sales and marketing expense.

They're generally find with a good efficacy profile good safety profile as long as the numerical change is in the range of $3 to four letters.

Interesting that I think that they believe in general that that type of change in vision is not noticeable to the patient.

On the other hand.

We as a company look at it as a combination of both of those and so that kind of minus three range or better I think based on what we anticipate the standard deviation of the trial might be.

George Elston: Non-operating expense net total 1.8 million in net loss was 12.6 million or 33 cents per share compared to a net loss of 18.4 million or 49 cents per share in the prior year period. Cash and investments at September 30, 2023 total 136 million compared to 144.6 million at December 31, 2022. We expect the cash, cash equivalent and investments on September 30, 2023 will enable us to fund our current and planned operations into 2025.

In a pivotal trial would likely be non inferior.

George Elston: In conclusion, we are pleased with I points progress in the third quarter and year to date and are well capitalized to advance our product pipeline to key value inflection points.

Jay Duker: I will now turn the call back over to Jay for closing remarks. Thank you, George. We believe EYP 1901 is a potentially paradigm shifting treatment for patients suffering from serious retinal diseases, providing unique benefits that may include delivery of a rollin of consistently over approximately nine months. A new mechanism of action to treat retinal disease beyond anti-vegetive ligand blockade, the potential for neuroprotection and anti-phibrosis, and a proven delivery technology with a positive safety profile.

Jay Duker: I will close by recapping key upcoming catalysts, including the top-line data from our Phase 2-2 clinical trial anticipated in early December, the dosing of the first patient and the Phase 2 Verona clinical trial of EYP-1901 and DMA in the first quarter of next year, and top-line data released from our Phase 2 pv of clinical trial in the second quarter of 2024. This remains an incredibly exciting time for EyePoint as we are well positioned to execute on our upcoming milestones and continue to transform the treatment landscape with innovative long-term solutions to improve both the vision and the lives of patients with serious retinal diseases. Thank you all very much for listening this morning.

Let me look.

I hope that was sufficient to anything else.

Nope that's cleared thank you very much.

Thank you so much. Your next question comes to your line of <unk>. Your line is now.

Thank you for taking my question. So J you just mentioned that you know you're focused on obviously delivering these data but also in the phase three so my question to you is and it also has to do with the competitor is you know how does the <unk> induction relate to the mechanism of T. K as in let M. D. And then can you maybe just talk about.

Why you think it is necessary for patients.

To do that induction when your competitors are doing a superiority study with just a single dose of <unk> <unk>.

Operator: I will now turn it over to the operator for questions. This is our most recent report.

Tyler Buren: Our first question comes from the line of Seller Van Buehred of PD comment. Your line is now open. Good morning, Graig Suvannavejh. Thanks very much for the call. I have a couple questions for you.

I would love to get your thoughts there.

Thanks, Yeah. Those are two great questions. Let me start with the induction first of all from a scientific perspective, it's unclear. If the deduction offers anything to the patients treated with you by P. 19 O. One we have pretty good preclinical data that shows that are.

Jay Duker: First one is I appreciate how transparent you guys have been with respect to your PCVA outcome scenario ranges for the WO2 trial ahead of the data, but we're these constructed in accordance with KOLs and can you elaborate on what the KOL feedback has been regarding what they need to see from the trial, perhaps the preview of source of the upcoming KOL event. And then the second question is upon positive data, can you talk about how quickly you would be able to start the phase three program and is it possible to get the top line data in accelerated fashion or should we think of it being a more traditional WO2 AMD phase three program timeline? Thanks, Tyler. Appreciate the questions in your interest.

Drug as Bible available in accord of animals within minutes of injection and reaches therapeutic levels in hours.

On the other hand, we've set out from the beginning to U Z Y P 19 O. One S. A maintenance therapy for previously treated wedding M D patients.

The decision to do the Reinjection is something that came up with our discussions with the F. D. A around the structure of the phase three pivotal trials.

When we had our type C meeting the F. D. A was certainly agreeable to us using eylea as our control interface Street and when we discussed on label Eylea. The F. D. A's response was yeah.

Jay Duker: First of all, with respect to the BCVA ranges, so there's really kind of three ways to look at this. And the first way is what does the FDA want? And that's pretty clear, not the non-afferiority margins got to be minus 4.5 letters. You can't cross it with your confidence intervals. And depending on your end of your study and your standard deviation, you could come pretty close to 4.5 and get a result.

Yes. After you re induce the patience you can go to every other month on label Eylea and the rationale was the patience you enroll in that trial may be under treat it in.

Therefore, before you allow them to go to every other month you Gotta <unk>.

Jay Duker: But the second part of what you ask is what does the KOLs want? And interestingly, when you ask them, I'm sure you have, they're generally fine with a good efficacy profile, a good safety profile, as long as the numerical change is in the range of three to four letters. It's interesting that I think that they believe in general that that type of change in vision is not noticeable for the patient. On the other hand, we as a company look at it as a combination of both of those, and so that kind of minus three range were better.

<unk> and then we had to Reengage D F D, a and said well if we're gonna <unk>.

Make an assumption that somebody size or under treated in the real world, which we think is probably true we'd like to <unk> all the patients in the study and.

And they were agreeable to that.

What's that did however, as you may be aware you could have a nine month efficacy and pointed in wet M. D study.

But our nine months doesn't start ticking until after the <unk> load of Eylea. So what it was the tradeoff here was we needed to do and are pivotal trial, the efficacy and point out approximately one year.

We thought that was a a fair trade off to be able to level, the playing field and make sure that we worked allowing.

Jay Duker: I think based on what we anticipate the standard deviation of the trial might be, in a pivotal trial would likely be non-inferior, and meet the KOL's expectations. Of course, we don't know what the results are yet. We'll know it approximately a month, but there's reasons to believe that we could do considerably better than that.

Relatively undertreated patients to flood the white connect you to one arms.

So it really isn't a scientific reason I'd say, it's a regulatory reason in a derisking reason that we're <unk>.

So that I think gets into the second question <unk> why induction again, I think I've covered that the our decision to do this you know.

Jay Duker: Second question was on the start of the phase three with good to great data. We believe we can start the first phase three trial in the second half of next year. It may be closer to the fourth quarter. You know, we haven't really zeroed in on that. Suffice it to stay the company has been really focused on phase three prep for basically the last nine months. And there's a lot to do to get ready, and we continue to be on track for our goal to start in the second half of next year.

I think more typical noninferiority phase three is again a comes out of our discussions with the F. D. A N. A derisking. We think that this is the fastest and least risky pathway to F. D a approval.

May I remind you that remember we had a type C meeting with F. D. A laying out the phase two plans, which would inform phase three.

And so that's also a big driver of focus going into.

Jay Duker: From an accelerated perspective, I think the trouble with unmasking early is you penalize yourself with a higher end. And, you know, cost and speed is critical here. And if our statistics suggest we can do the phase threes with relatively low ends, I think it's best to get them done right and get them done fast as opposed to, you know, be penalized for an early look. I hope that was sufficient.

The the phase III next year.

<unk> very helpful. Just one more question if I may could you talk about the dose response there are two doses in this study. So just curious what would you expect should we expect any dose response.

Yeah, and then you know if let's say if there is no dose response I'm just curious like how you will decide on the adults to pay for it. Thank you Yep. That's another great question Yahoo, and what are we really don't know if there will be a dose response, because it's certainly possible that are two milligram dose will work.

Unknown Executive: Anything else? No, that's clear. Thank you very much.

Efficiently to shut down the receptor for up to nine months and therefore any additional drug may not give you additional benefit.

Unknown Executive: Thank you so much.

So I would say, we're we're as a company a little bit agnostic to that I mean, it's nice to show a dose response and if there's some validation to that understandably on the other hand, if both are two milligram dose or three milligram dose work great.

Unknown Attendee: Your next session comes from the line up. You have engineer of good and high.

Yatin Suneja: Your line is now open. Thank you for taking my question. So Jay, you just mentioned that you know you'll focused on obviously delivering these data, but also in the phase three. So my question to you is, and it also has to do with the competitor is, you know, how does the ILEA induction relate to the mechanism of TKIs in let AMD. And then can you maybe just talk about why you think it is necessary for patient. To do that induction when your competitors are doing a superiority study with just a single dose, a flip receptor, the comparison. So love to get your thoughts there. Thanks.

Great and they're essentially the same we would opt to go with the two milligram dose approximately in our pivotal trial against a lower dose most likely around one milligrams.

Jay Duker: And those are two great questions. Let me start with the induction. First of all, from a scientific perspective, it's unclear if the induction offers anything to the patients treated with you by 1901. We have pretty good preclinical data that shows that our drug is bioavailable in the core of animals within minutes of injection and reaches therapeutic levels and hours. On the other hand, we've set out from the beginning to use EYP 1901 as a maintenance therapy for previously treated wet AMD patients.

What that will do a courses enable us if if successful to have fewer inserts in the eye and lowered the cards.

Okay. Thank you so much.

Thank you. So much. Your next question comes from the line has changed drinking attaches account your my account.

For taking my questions <unk>. The first is just touching on the P. C. D. A question K I think it in your prepared remarks, you said a P. C. P. A letter change differences three letters are better would be good and I think investors are generally align with that the most pushback I've gotten is on <unk>.

Jay Duker: The decision to do the re-induction is something that came up with our discussions with the FDA around the structure of the phase three pivotal trials. When we had our type C meeting, the FDA was certainly agreeable to us using ILEA as our control in the phase three. And when we discussed on label ILEA, the FDA's response was, yes, after you re-induced the patients, you can go to every other month on label ILEA.

Minus three to minus four letter scenario I was curious to see if you have any thoughts on that scenario is it is it base case or the hope that it would be better than that and similar.

Similar to that in this scenario, where you get a minus three letter difference what's that Sig <unk>.

<unk>, a standard deviation better than what we've seen with take P. D S.

Sure Great questions Jennifer Thanks, So the best corrected visual acuity of three or less a difference really would be I think kind of a clear pathway in everybody's mind, if we can replicate that in the pivotal trials.

Jay Duker: And the rationale was, the patients you enroll in that trial may be under treated. And therefore, before you allow them to go to every other month, you've got to read. Houston. Made sense, and then we had to re-engage the FDA and said, well, if we're going to make an assumption that some of these eyes are under treated in the real world, which we think is probably true, we'd like to re-induce all the patients in the study.

Minus three to minus four is a kind of a theoretical range where.

One could argue that with a minus let's say three and a half letter difference and a large enough and and a small enough standard deviation that that could be statistically noninferior.

Jay Duker: And they were agreeable to that. What that did, however, is you may be aware you can have a nine-month efficacy end point in the end point was the trade-off here was we needed to do in our pivotal trial, the efficacy end point out approximately one year. We thought that was a fair trade-off to be able to level the playing field and make sure that we weren't allowing relatively under-treated patients to flood the EYP-1981 arms. So it really isn't a scientific reason. I'd say it's a regulatory reason in a de-risking reason that we're re-inducing.

But then you're getting into points here, where would it be commercially successful.

So Wally would meet that first bar of.

F D. A approval it may not meet the second bar of what the K O L. Swanton, perhaps as you say what the investment community you might Wanna see as a result.

So I would say you know again centering on the three letters are better I think that beats everybody's test for success here.

I remind everyone that you know we were minus 2.5 letters in the phase one at.

At six months after the 19 O one was injected.

Jay Duker: So that I think gets into the second question. You know, why induction? Again, I think I've covered that. The our decision to do this, you know, I think more typical non-inferiority phase three is again a comes out of our discussions with the FDA in a de-risking. We think that this is the fastest and least risky pathway to FDA approval. I remind you that remember we had a type C meeting with FDA laying out the phase two plans which would inform phase three.

And one would expect and of course, we don't know this yet, but one would expect the eylea control arm to be relatively stable. After the load between you know weeks eight and week 32, and if it is and we can replicate minus 2.5 again I think that that would be really <unk>.

Outstanding results.

So the words again, you know base case and you know, it's it's again I think a lot of this depends on what the view of what the what what would need to do to advance to drug into you know pivotal trials.

And one could see with a very tight standard deviation that Steven minus three letters would be statistically significant. So you mentioned the P. D. P. D. S standard deviations in again, if you go back and look at the pivotal trials and wedding M. G.

Unknown Executive: And so that's also a big driver of focus going into the phase three next year. Very helpful.

Jay Duker: Just one more question if I may. Could you talk about the dose response? There are two doses in this study. So just curious, what would you expect? Should we expect any dose response? And you know, if let's say if there is no dose response, just curious like how you will decide on the dose to take forward. Thank you.

But I think basically every one since I Leah was approved was done on a noninferiority basis and treatment of patients and generally had standard deviation to the change in visual acuity of around 12, 12 letters, that's because their treatment naive somebody's response on my stomach.

Jay Duker: Yep, that's another great question, gotten. And we really don't know if there will be a dose response because it's certainly possible that our two milligram dose will work efficiently to shut down the receptor for up to nine months. And therefore any additional drug may not give you additional benefit. So I would say we're as a company, a little bit agnostic to that. I mean, it's nice to show a dose response. And there's some validation to that understandably.

The P. D. S pays three enrolled previously treated patients like we did but they limited the length of time to diagnosis to nine months prior.

So some of those eyes were still relatively early in their treatment and still perhaps being treat an extended they wanted a stable kind of pace of their treat of their disease yet.

They had 7.1 letter standard deviation.

So we have reasons to believe that because of our.

Jay Duker: On the other hand, if both are two milligram dose and are three milligram dose work great. And they're essentially the same. We would opt to go with the two milligram dose approximately in our pivotal trial against a lower dose, most likely around one milligrams. What that would do, of course, is enable us if successful to have fewer inserts in the eye and lower the cogs.

Rome it of ice that had the disease longer than nine months are suggesting they'd be more stable the our standard deviation could be lower than that.

Unknown Executive: Thank you so much.

That answer the questions yeah.

Yeah. It does if I could add one more <unk> your competitor receipts are announced that they received an agreement under their superiority trial design. This morning, <unk> <unk>. It seems like good news for the overall space given the <unk> World. We're in but I'm wondering if you have any takes on that.

Jennifer Kim: Your next question comes from the line of Jennifer Kim of Catherine Fitzgerald.

Well, yeah, and again that was just announced this morning with no details, but at a high level. This is great news, it's great news for all of the T. K I companies because it shows that the F. D. A is willing to work with us to advance this new paradigm.

Jennifer Kim: Your line is now open, for taking my questions. I have two. The first is just touching on the BCBA question. Jay, I think you're in your prepared remarks, you said a BCBA letter changed a difference of three letters or better would be good. And I think investors are generally aligned with that. The most pushback I've gotten is on minus three to minus four letter scenario. So I was curious to see if you have any thoughts on that scenario.

Jennifer Kim: Is it is a base case or the hope that it would be better than that? And similar to that in this scenario, where you get a minus three letter difference, would that say have to assume a standard deviation better than what we've seen with, say, PDF? Sure, great questions, Jennifer. Thanks. So the best corrected visual acuity of three or less difference really would be I think kind of a clear pathway in everybody's mind, if we can replicate that in the pivotal trials.

Into the clinic.

And as we know it's it's great for the space you know when when when Investor see that there's a clear pathway to approval then things are derisk from.

Jennifer Kim: Minus three to minus four is kind of a theoretical range where one could argue that with a minus let's say three and a half letter difference in a large enough and in a small enough standard deviation that that could be statistically non-inferior. But then you're getting into a point here where would it be commercially successful. So while it would meet that first bar of FDA approval, it may not meet the second bar of what the KOLs want and perhaps as you say what the investment community might want to see as a result.

From our perspective, we're very comfortable with her face to design.

And if we get good to great results at this point I think our phase III design, which the F. D. A has already seen and commented on and <unk> type C meeting I think that's still would represent <unk>.

The fastest lease risky way to get approval for our drug.

<unk> last comment about this though is is once we are able to see the details of all the spot that as an octopus received we will like any company should do is you know take a look at our program and see if there's any learnings from what they're doing but I have two against state we're very calm.

<unk> with our approach to the pivotal trials and pathway to approval.

Mmk that's helpful. Thanks for taking my question. Thank you.

How much. Your next question comes from the line up for me and Casey Okay. Yeah My account.

<unk> may I ask a question.

Jennifer Kim: So I would say, again, centering on the three letters are better. I think that beats everybody's test for success here. I remind everyone that we were minus 2.5 letters in the phase one at six months after the 1901 was injected. And one would expect, and of course we don't know this yet, but one would expect the ILEA control arm to be relatively stable after the load between weeks eight and week 32.

Okay.

Jennifer Kim: And if it is, and we can replicate minus 2.5 again, I think that that would be really an outstanding result. So the words again, and you know, base case, and it's again, I think a lot of this depends on what the view of what we need to do to advance the drug into, you know, pivotal trials. And one could see with a very tight standard deviation that even minus three letters would be statistically significant.

Maybe we could go back to Coney after the next one.

Alright.

Your next question comes from the line.

Sharon.

[laughter].

I couldn't.

Plus my name that was called the thank you for taking the question that I have a coupon on 20 301 wanted to ask for the rationale for <unk>.

<unk> for this.

Product and the specific with how does it fit with 19 O one strapped to chicken that there could be some overlapping indications.

Oh, that's Daniel that's a great question 20, 301 is based around the molecule. That's been studied into phase two by a company called <unk>, we acquired their assets and their lead product. It could be 90 707 eight was delivered subcutaneously.

For diabetic macular edema and for a diabetic retinopathy.

Jennifer Kim: So you mentioned the PDS standard deviations. And again, if you go back and look at the pivotal trials and wet AMG, I think basically everyone, since ILEA was approved, was done on an on-of-fear-ority basis and treatment IE patients and generally had standard deviations to the change in visual acuity of around 12 12 letters. That's because their treatment IE, some eyes respond, some eyes don't. The PDS phase three enrolled previously treated patients like we did, but they limited the length of time to diagnosis to nine months prior.

And it showed really promising anatomic results, although the visual results did not enable the company to really go forward into good little trials.

This drug activates tie too and by activating tied to you stabilize blood vessels and you Downregulate <unk> <unk> and you may be aware that the <unk> is a vice specific that blocks vet chef and blocks <unk>.

That pathway of and two blockage is validated.

Jennifer Kim: So some of those eyes were still relatively early in their treatment and still perhaps being treated extended. They weren't at a stable kind of pace of their treat of their disease yet. They had 7.1 letter standard deviation. So we have reasons to believe that because of our enrollment of eyes that had the disease longer than nine months, are with suggesting they'd be more stable. Our standard deviation could be lower than that. That's the question. Yeah, it does.

And we believe that it can be 9778 now you might be 20 301.

May be a better way to block that pathway by activating tied to.

Secondly, we can now deliberate sustained release. So these by specific molecules still require relatively frequent injections and we believe we can deliver at therapeutic levels for over six months with a <unk> with a single injection of 20 301.

Jay Duker: If I could one more, your competitor received or announced that they received an agreement under their superiority trial design this morning. Net net, this seems like good news for the overall space given the post draft guidance world we're in, but I'm wondering if you have any takes on that. Yeah, and again, that was just announced this morning with no details, but at a high level, this is great news. It's great news for all of the TKI companies because it shows that the FDA is willing to work with us to advance this new paradigm into the clinic.

So how does it fit and will that remains to be seen.

I think that we could develop it and tested and a noninferiority fashion to get a label against the standard of care for either wet M D or D me or both.

Or we could choose to go for a superiority trial using it in conjunction with any of the venture.

That of course.

Would be perhaps riskier because the anti vet chefs are so effective such a really high ceiling on.

On the other hand, if one is successful with that approach.

Oh, you would likely have a multibillion dollar product because doctors would relish the opportunity to do even better than anti venture off alone how would it fit into <unk> 19 O. One.

Jay Duker: And as we know, it's great for the space. You know, when investors see that there's a clear pathway to approval, then things are de-risk. From our perspective, we're very comfortable with our phase two design. And if we get good to great results, at this point, I think our phase three design, which the FDA has already seen and commented on. And through our type of meeting, I think that still would represent the fastest, least risky way to get approval for our drug.

<unk> is highly speculative because we've got a long halfway to go with 20 301 shorter pathway with with 19 O. One, but you could envision a day when both have approval a stand alone in this combo and one could do it one of each in a single injection.

Obviously that there's a long pathway to that and a lot of permutations that we're going to look at but the in a nutshell. What we believe we can do with 20 301 is activate the tie to pathway secondarily inactivate answer to <unk> to do it in a sustained release fashion with a derisk molecule.

Jay Duker: Again, last comment about this though is, is once we are able to see the details of the spot that the doctors received, we will like any company should do is, you know, take a look at our program and see if there's any learnings from what they're doing. But I have to against state, we're very comfortable with our approach to the pivotal trials in pathway to approval. Okay, that's helpful. Thanks for taking my question. Thank you. Thank you so much.

Alright got it thank you.

Unknown Executive: Your next question comes from the line up for me. Here's the opherent.

So much.

Your next question comes from the line <unk>.

Thank you for taking my questions.

Couple of quick ones, So I guess.

For the web M D program and following the dog to read out which are you requesting Orlando face the trial would be Thursday to further <unk>.

Unknown Executive: Your line is now open. You may ask your question.

That's our plan.

In fact, we would plant currently on having both a clinical interface to an a C. M C interface to to gain alignment in both of those areas.

Okay, Gotcha, and the potential telling me about that.

Unknown Executive: Maybe we could go back to calling after the next one. All right.

I would say late in the first quarter of next year may bleed into early second quarter of next year, depending again, how soon we can get all the clinical tables from W. Two in a format that we can <unk> submit.

Daniil Gataulin: Your next question comes from the line of talent, good to lead a chart in. Please go ahead. I couldn't hear. That was my name. That was called. Yeah, I think if I take in the question, I have a coupon on 2301 wanted to ask for the rationale for for for this. Product and specifically how does it fit with 1901 strategy given that there could be some overlap in education. Thanks. Thank you.

Okay, great. Thank you.

Submitting step here.

Okay, Gotcha, and <unk> <unk> <unk> collaboration what updates should it should be be expecting.

From that program in 2024.

Daniil Gataulin: Thanks, Daniel. That's a great question. 2301 is based around the molecule that been studied into phase two by a company called ARPO. We acquired their assets and their lead product, AKB 9778 was delivered subcutaneously for diabetic macular edema and for diabetic granopathy. And it showed really promising anatomic results, although the visual results did not enable the company to really go forward into biblical trials. This drug activates TIE 2 and by activating TIE 2, you stabilize blood vessels and you down regulate angel pleatin 2 or angel 2.

Thanks for that question John you know that's a good question and the answer is as we said before we're really excited about the collaboration we're really excited about the molecule getting compliment inhibitors to last several months of therapeutic levels in the eyes of <unk>.

Ouch.

If it wasn't a challenge you'd see them already however, we've been great progress.

And we remain optimistic that we will be able to sustain release, a compliment inhibitor, but until we have really are confident in our formulation and our ability to do this consistently we're not gonna make any public statements around that so I would say that again, we are still working on it we have made great progress we have some.

Daniil Gataulin: Now you may be aware that the bismo is a bi-specific that blocks vetchf and blocks angel 2. So that pathway of angel 2 blockage is validated. And we believe that AKB 9778 now, EYP 2301, may be a better way to block that pathway by activating TIE 2. Secondly, we can now deliver it sustained release. So these bi-specific molecules still require relatively frequent injections. And we believe we can deliver at therapeutic levels for over six months with a sync injection of 2301.

Really great scientists working on this but it's not an easy task to accomplish.

Yeah, Shaun maybe I can add to that because if you. If you look at how we are cadence on disclosure.

We've just disclose 20 301, this past quarter, because we've gotten to a point, where it formulates and we're in a position to.

To move it into those preclinical.

Programs and I think you should think the same for the compliment space as well once we get that formulation that we know works and has the right window.

We'll start talking about it a little more publicly on what that balance it looks like.

Daniil Gataulin: So how does it fit in? Well, that remains to be seen. I think that we could develop it and test it in a non-inferiority fashion to get a label against the standard of care for either wet MD or DMA or both, or we could choose to go for a superiority trial using it in conjunction with an anti-vegetia. That of course would be perhaps riskier because the anti-vegetia are so effective. It sets a really high ceiling.

Okay Gotcha. Thank you and last one from me is that about the cash runway into 2025.

Daniil Gataulin: On the other hand, if one is successful without approach, you would likely have a multi-billion dollar product because doctors would relish the opportunity to do even better than anti-vegetia alone. How would it fit into EYP 1901? You know, you can highly speculative because we've got a long pathway to go with 2301, shorter pathway with 1901, but you could envision a day when both have approval as standalone and as combo. And one could do it one of each in a single injection.

Include potential pivotal three phase three trials.

D S. All now that they're looking to start a second half.

Thanks for that question trunks of our faith I'm, sorry, our cash guidance into 2025.

Includes the ongoing phase twos the plan <unk>.

N D M, a which is the Verona trial, which will we expect to start in Q1, along with a significant amount of phase three prep.

To start to be in a position to start the trials.

Sometimes second half of next year. It does not include.

The the actual clinical trial costs for the Pivotals and as we talk previously that's something that we're going to look to a range of options to fund.

Which includes potential equity wait raise we've got strong strategic partner interest and some other leavers that we can pull and we'll be talking about that you know over the coming months on our plans to fund that really after.

His two results.

Okay. Thank you again for taking my question. Thank you.

Daniil Gataulin: Obviously, there's a long pathway to that and a lot of permutations that we're going to look at. But in the nutshell, what we believe we can do with 2301 is activate the tie-to pathway, secondarily inactivate, and to do it in a sustainably fashion with a de-risk molecule. All right, you got it. Thank you. Don't watch.

How much the next.

Question comes from the line is Neil Tennessee Line Company now.

Now open.

Question at the end of my course, you'll probably will be focusing on the potential future.

330.

The first one is that the <unk> one of your latest the presentation you have.

Laid out for scenarios in terms of the faith three of different P. C V. A outcomes I'm. Just curious are based on those that assumptions what might be your thoughts in terms under each scenario what the 833.

Unknown Executive: Your next question comes from the line of Shantkin of Jones. Reading, please go ahead. Thank you for taking my questions. I just have a couple quick ones. I guess for the WebAMD program following the target to read out, would you be requesting on End of Phase 2 trial with FDA to further guide the Phase 3 trial design? That's our plan. In fact, we would plan currently on having both a clinical end of phase two and a CMC end of phase two to gain alignments in both those areas.

<unk> might be then I have a follow up.

Yeah, now that you're talking about on the B C V. A measures does that right for all 1.0, all the way to minus four yeah.

Yeah, well, if I made that actually were.

Our interpretation of the phase two outcomes of where they might land and what they might mean for those those outcomes without knowing the standard deviation of the change in addition to Judy.

Unknown Executive: Okay, and the potential timing of that meeting. I would say late in the first quarter of next year, may bleed into early second quarter of next year, depending again, how soon we can get all the clinical tables from W2 in a format that we can submit.

We can't predict the size of the trials.

But.

You can run it into a statistics package and we've certainly done that if we're minus one letter worse than the Eylea control and the standard deviation is seven or less we could do pivotal trials that might involve as few as.

Unknown Executive: Okay, great, thank you. Okay, what's the rally bio complement inhibitor collaboration? What updates should it should be the expecting from that program in 2024? Thanks for that question, Sean. You know, that's a good question. And the answer is, as we've kind of said before, we're really excited about the collaboration. We're really excited about the molecule. Getting complement inhibitors to last several months at therapeutic levels in the eyes of challenge. If it wasn't a challenge, you'd see them already.

250 to 300 patients.

So it's fluid because we don't know those results yet.

But there's a second consideration I think for most of these trials that when you're doing treatment naive patients. When the standard deviation is larger companies end up doing 500, 600 700 patient trials.

But that's because not only the standard deviation because the F. D. A requires a certain number of patients for safety.

Unknown Executive: However, we've been great progress and we remain optimistic that we will be able to sustain release a complement inhibitor, but until we have really our confidence and our formulation and our ability to do this consistently, we're not going to make any public statements around that. So I would say that again, we're still working on it. We have made great progress. We have some really great scientists working on this, but it's not an easy task to accomplish.

So the F. D. A requires that you submit in Europe able to submit with one year efficacy data App of your second trial, you don't need it to your safety to submit.

But at the one year you need to have 300 patients treated with your go to market dose or higher.

Ultimately you need approximately 400 patients treated with your go to market dose or higher for safety. So that's another consideration for the end of the trial and that might.

Unknown Executive: Yeah, Sean, maybe I can add to that because if you look at how we, you know, our cadence on disclosure, you know, we just disclosed 23 or 1 this past quarter, because we've gotten it to a point where it formulates and we're in a position to move it into those preclinical programs. And I think you should think the same for the complement space as well. Once we get that formulation that we know works and has the right window. So we'll start talking about it a little more publicly on what that pathway looks like.

Suggests that we would maybe not to have one to one to one randomization and the pivotals and have more patience and the higher dose to reach those safety measures knowing that the statistics would allow a smaller number as I said already you know our view is to do this as quickly as safely as derisks.

It is less expensive as possible and that's how we're gonna view, all the options and the pivotal trials.

George Elston: Okay, I got you. Thank you. And last one for me is that about the cash runway into 2025. Does that include potential 303 phase three trials in wedding and the as well? Now that you're looking to start in second half. Yeah, thanks for that question, Sean. So our face, I'm sorry, our cash guidance into 2025 includes the ongoing phase twos. The plan phase in DME, which is the Verona trial, which will we expect to start in Q1 along with a significant amount of phase three prep to start to be in a position to start the trials sometimes second half of next year.

Okay, Great. That's very very helpful. And you mentioned earlier that the fate three also incorporate the <unk> options cause could you elaborate a little bit more <unk> so what.

<unk> <unk> <unk>.

Any details on that sure yep, Thanks, and we've been I think we've been very consistent from the start.

Even though we have in vivo and in vitro evidence that these <unk> 19, one insurance will release, a therapeutic levels for approximately nine months, we've done enough Tox studies to show that even if we reinject earlier than that where.

George Elston: It does not include the actual clinical trial costs for the pivotals. And you know, as we've talked previously, you know, that's something that we're going to look to a range of options to fund, which includes potential equity way raise. We've got strong strategic partner interest and some other levers that we can pull. And we'll be talking about that, you know, over the coming months on, you know, our plans to fund that really after the phase two results. Okay, thank you again for taking a good question. Thank you.

Very safe area for toxicity of rolling and number of inserts. In fact, we have not found the maximally tolerated level of rolling with animal wise. So from a safety perspective, it's not a problem why did we choose six months I think it's simple that's what retina specialist <unk> <unk>.

They want flexibility to dose drugs when they want a dose.

And wall, it's clear that some ice can go longer than six months remember in our <unk> and our phase one trial, rather we had a third of the eyes made it a year without supplement.

Unknown Executive: Thank you so much. The next question comes in terms of the phase three of different BCVA outcomes. I'm just curious, based on those assumptions, what might be your swap in terms under each scenario, what the phase three study size might be, then I have a follow-up. Yeah, you're talking about on the BCVA measures, right from one point zero on the way to my full. Yeah, yeah, if I may, that does actually were our interpretation of the phase two outcomes of where they might land.

We're going for the label of every six months, because we want to give the doctor's flexibility to dose that often should they choose to.

Okay, Great. That's helpful. And then maybe just add one more that regarding a spot from the competitors and use that money was that something you guys also consider or it still depends.

Well, yeah, well again, I think I did address this earlier, but I'll reiterate we have what we believe is in agreement with the F. D. A as in writing that we have an acceptable protocol for our pivotal trials.

If that is the fastest least risky way to proceed that's our plan hen we've seen nothing at this point alter that obviously, it's dependent on good to great data from <unk>.

Unknown Executive: And what they might mean for those outcomes, without knowing the standard deviation of the change in visual maturity, we can't predict the size of the trials. But, you know, you can run it into a statistics package and we've certainly done that. If we're minus one letter worse than the Ilya control, and the standard deviation is seven or less, we could do pivotal trials that might evolve as few as 250 to 300 patients.

But there may be <unk>.

Learning from other companies approach and will be studying that to see if there are any learnings for us so until the details are out.

I really can't make any comment on that except to reiterate once more we're very comfortable with where our program is that right now.

Okay, great and congrats on the other progress and local or and or December.

Thank you so much.

Next question comes from the line <unk> E T V.

Yeah My email.

Unknown Executive: So, it's fluid because we don't know those results yet. But, there's a second consideration, I think, for most of these trials, that when you're doing treatment naïve patients when the standard deviation is larger, companies end up doing 500, 600, you know, seminar to patient trials. But, that's because not only the standard deviation, because the FDA requires a certain number of patients for safety. So, the FDA requires that you submit, and you're able to submit with one year efficacy data of your second trial, you don't need to do your safety to submit.

Thank you for taking my question. So my question is by positioning 19 O. One is and maintain a therapy.

Wow your competitors seems to target treatment Martin patient, adding their faith <unk> does that mean, you could potentially lose part of the market in the future.

<unk> could you use 19 014 treatment patients as well thank you so.

If we get a label for maintenance therapy and the label includes follow.

We use of 19, one after induction with.

Unknown Executive: But, at the one year, you need to have 300 patients treated with your go-to-market dose or higher. Ultimately, you need approximately 400 patients treated with your go-to-market dose or higher for safety. So, that's another consideration for the end of the trial, and that might, you know, suggest that we would maybe not do a one-to-one randomization in the pivotals, and have more patients in the higher dose to reach those safety measures knowing that the statistics would allow a smaller number.

Or any anti VEGF, let's say hypothetically.

I think doctors, knowing the retina specialist community the way I do I think doctors will try it earlier than after three induction doses in some cases, if we're safe effective and tolerable.

I think the argument might be why not use it after a second induction her first induction dose will it be used a solo therapy. Initially I think data needs to be shown that that that it's effective that way.

Unknown Executive: As I've said already, you know, our view is to do this as quickly, as safely, as de-risk, it is less expensive as possible, and that's how we are going to view all the options in the pivotal trials.

So again the market share depends on a lot of things and once again one of the things we just talked about was reinjection.

And the hope and expectation is we would get a label for every six months reinjection.

Unknown Executive: Okay, great, that's very, very helpful. And you mentioned earlier that the Phase III also incorporates the regreement options of course. Could you elaborate a little bit more in terms of at least what you proposed, the regreement, any details on that? Sure, yeah, thanks. And we've been, I think we've been very consistent from the start. Even though we have in vivo and in vitro evidence that these EYP191 inserts will release at therapeutic levels for approximately nine months, we've done enough tox studies to show that even if we re-inject earlier than that, we're in a very safe area for toxicity of a rolinib and number of inserts.

The F D. A was clear that if we wanted a label for Reinjection, we needed to test reinjection in the pivotal trials and so I think that if that is the way our label reads. Eventually I think that will have an advantage also so it's hard to predict I will certainly admit that but once again, we are very comfortable with where our program.

That and the approach that we're taking and the retina community that we've talked to I think is in favor of the approach that were taken and if we get that label I think retina specialist will figure it out.

Yeah, maybe if I can add to that just keep in mind. The vast majority of the market has previously treated patients and the fact that we are going to be able to read those every six months is going to be meaningful on our label.

Unknown Executive: In fact, we have not found the maximally tolerated level of a rolinib and the animal ice. So from a safety perspective, it's not a problem. Why did we choose six months? I think it's simple. That's what retina specialists want. They want flexibility to dose drugs when they want to dose them. And while it's clear that some ice can go longer than six months, remember in our Phase I trial rather, we had a third of the ice made it a year without supplement. We're going for the label of every six months because we want to give the doctor's flexibility to dose that off and should they choose to.

And you know I think ultimately physicians will have the opportunity to use it sooner, but as we think about our approach in the market approach. You know, we're we're addressing a very significant portion of a $10 billion plus market. So we're we're comfortable with our pathway.

I could have one more church you know if that was an excellent point you made about you know for every newly diagnosed patient around a specialist probably has a dozen or more previously treated patients in your practice.

So once again from a recruitment perspective and from speed to filling a.

Trial, there's a lot more maintenance therapy patients out there than there is newly diagnosed and that's one of the many reasons why we chose at this pathway speed to approval.

Unknown Executive: Okay, great. That's helpful. And maybe just add one more of that regarding spots from the competitors news, not this morning. Was that something you guys also consider or the competitors? Well, yeah, again, I think I did address this earlier, but I'll reiterate, we have what we believe is an agreement with the FDA that's in writing that we have an acceptable protocol for our pivotal trials. If that is the fastest least risky way to proceed, that's our plan.

Thank you.

Is is could we see if colleen is still on the line and wants to ask a question. Yeah. She responded she's having issues Oh, a number of this morning. So she would find her later.

Okay Alright.

Alright, and we actually don't have any further questions.

Nine.

Yeah, Let me think.

Thank you for being in today's campaign.

Okay.

Give me one second everyone have a great day and thanks everybody.

Mmm.

Unknown Executive: And we've seen nothing at this point all to that. Obviously, it's dependent on good-to-great data from Davio too. But there may be learnings from other companies' approach and we'll be studying that to see if there are any learnings for us. So until the details are out, I really can't make any comment on that except to reiterate once more, we are very comfortable with where our program is at right now.

Unknown Executive: Okay, great. And congrats on the other progress and look forward in early December.

Mmm Mmm mmm.

[music].

Unknown Executive: Thank you so much.

Unknown Executive: Your next question comes from the line of each end of the H.U.B. Writing Company. Your line is now open.

Unknown Executive: Thank you for taking my question. So my question is by positioning 1901 as a maintenance therapy. Well, your competitor sings to target treatment not youth patient in their FA3 trial. Does that mean you could potentially lose part of the market in the future? I mean, could you use 1901 for treatment not youth patients as well?

Jay Duker: Thank you. So, if we get a label for maintenance therapy, and the label includes follow the use of 191 after induction with Ilya or any anti-vegetae, let's say hypothetically. I think doctors knowing the retina specialist community the way I do, I think doctors will try it earlier than after three induction doses in some cases. If we're safe, effective and tolerable, I think the argument might be why not use it after a second induction or first induction dose.

Jay Duker: Will it be used as solo therapy initially? I think data needs to be shown that it's affected that way. So again, the market share depends on a lot of things. And once again, one of the things we just talked about was re-injection. And the hope in expectation is we would get a label for every six months re-injection. The FDA was clear that if we wanted a label for re-injection, we needed to test re-injection in the pivotal trials.

Jay Duker: And so I think that if that is the way our label reads eventually, I think that will have an advantage also. So it's hard to predict. I will certainly admit that. But once again, we are very comfortable with where our program is at and the approach that we're taking. And the retina community that we've talked to I think is in favor of the approach that we're taking. And if we get that label, I think re-injection specialist will figure it out.

Jay Duker: Yeah, maybe if I can add to that, just keep in mind the vast majority of the market is previously treated patients. And the fact that we are going to be able to read those every six months is going to be meaningful on our label. And I think ultimately physicians will have the opportunity to use it sooner. But as we think about our approach and the market approach, we're addressing a very significant portion of a $10 billion plus market.

Jay Duker: So we're comfortable with our pathway. And I could have one more, George, you know, that was an excellent point you made about, you know, for every newly diagnosed patient, a rather specials probably has a dozen or more previously treated patients in their practice. So once again, from a recruitment perspective and from speed to filling a trial, there's a lot more maintenance therapy patients out there than there is newly diagnosed. And that's one of the many reasons why we chose in this pathway.

Unknown Executive: Speed to approval. Thank you. Is could we see if Colleen is still on the line and wants to ask a question? Yeah, she responded. She's having issues a number of all this morning. So she's we'll find her later. All right.

Operator: And we actually don't have any further questions in the queue at this time. So the gentleman, thank you for participating in today's conference. This doesn't include your webcam on your program. Give me now disconnect everyone. Have a great day. Thanks, everybody. [inaudible] I'm not sure. I'm not sure.

[music].

Good morning, he might even be late I'll be your conference operator.

Today at this time I would like to welcome everyone to isolate pharmaceuticals, great work in 2023 financials, where somebody says Oh, Great Development Conference call. There will be a question and answer session to follow on the condition of the benchmark.

Please be advised that this call has been appointed as the company's request.

I would now like to turn the call over to George Ellison, Executive Vice President and Chief Financial Officer.

Pharmaceuticals. Please go ahead.

Thank you and thank you all for joining us on today's conference call to discuss I point Pharmaceuticals third quarter 2023 financial results and recent corporate developments with me today is Dr. Jay Duker, President and Chief Executive Officer.

Jay will begin with a review of recent corporate updates and discuss the ongoing phase II clinical trials for <unk> thousand 19 O. One I will close with commentary on the third quarter 2023 financial results and we will then open the call for your questions earlier.

Earlier. This morning, we issued a press release detailing our financial results and recent operational developments a copy of the release can be found in the investors tab on the corporate website www Dot <unk> pharma dot com.

Before we begin our formal comments I'll remind you that various remarks, we will make today constitute forward looking statements for the purposes of the Safe Harbor provisions under the private Securities Litigation Reform Act of 1095. These.

These include statements about our future expectations clinical developments and regulatory matters and timelines the potential success of our products and product candidates financial projections, and our plans and prospects.

Actual results may differ materially from those indicated by these forward looking statements as a result of various important factors, including those discussed in the risk factors section on our most recent annual report on Form 10-K, which is on file with the SEC and in other filings that we may make with the SEC in the future.

Forward looking statements represent our views as of today only while we may elect to update these forward looking statements at some point in the future. We specifically disclaim any obligation to do so even if our views change.

Therefore, you should not rely on these forward looking statements as representing our views as of any date subsequent to today.

I'll now turn the call over to Dr. Jay Duker, President and Chief Executive Officer of <unk> Pharmaceuticals.

Thank you George.

Everyone and thank you for joining us to discuss <unk> continued execution towards our milestones as we work to bring first in class therapeutics and delivery technologies to patients suffering from serious retinal diseases.

In the third quarter, we both advanced and expanded our product pipeline with the announcement of positive mask safety data in our ongoing <unk> and <unk> phase III clinical trials for our lead product candidate <unk> hundred one which is the small molecule for rolling up and our proprietary bio <unk>.

<unk> <unk> technology.

As well as the unveiling of a new preclinical program <unk> 301.

<unk> 301 delivers a promising tied to activator, which you approach a fib.

Formerly known as <unk> 900, 778 formulated in <unk> E to potentially improve outcomes in wet age related macular degeneration or wet AMD and diabetic eye disease.

It's an exciting time at <unk> as our <unk> 19 O. One clinical trials approach key data events with top line phase two <unk> trial results anticipated in early December and Pavia results in Q2 of next year.

And as we plan to initiate a third phase III trial in diabetic macular edema or <unk> in Q1 of 2024.

I'll now review, our recent programming corporate updates and give an overview of upcoming catalysts.

Turning to our lead program <unk> 90 to one is being advanced as a potentially paradigm shifting treatment for patients suffering from <unk> mediated retinal diseases.

19, one is delivered with a single intravenous <unk> injection in the physician's office similar to the current FDA approved anti VEGF biologic treatments.

Lee Wei: Good morning, my name is Lee Wei and I'll be your conference author later today. At this time, I would like to welcome everyone to the EyePoint Pharmaceuticals, the recorder in 2023, financial source of recent corporate development conference call. There will be a question and answer session to follow at the completion of those great remarks.

<unk> 90, you don't want is immediately bio available featuring an initial burst of drug followed by near constant zero order kinetic release for approximately nine months.

It might be 90 to one delivers we're rolling up a selective and patent protected tyrosine kinase inhibitor formulated in a solid insert using our proprietary sustained release bio erodible <unk> technology.

Unknown Executive: This is the advice of this call is being recorded at the company's success.

George Elston: I would not like to turn the call over to George Elston, Executive Vice President and Chief Financial Auditor, on the EyePoint Pharmaceuticals. Please go ahead. Thank you, and thank you all for joining us on today's conference call to discuss eye point pharmaceuticals third quarter 2023 financial results and recent corporate development. With me today is Dr. Jay Duker, President and Chief Executive Officer. Jay will begin with a review of recent corporate updates and discuss the ongoing phase two clinical trials for EYP 1901.

We're rolling it brings a new mechanistic approach to the treatment of VEGF mediated retinal diseases by acting as a pan VEGF receptor blocker blocking all bet Jeff isoforms.

George Elston: I will close with commentary on the third quarter 2023 financial results. We will then open the call for your question. Earlier this morning, we issued a press release detailing our financial results and recent operational development. A copy of the release can be found in the Investors tab on the corporate website, www.eyepointfarma.com.

We expect <unk> 19 O one with its new MLA and sustained drug delivery for up to nine months to meaningfully reduce treatment burden and the majority of wet AMD patients, while keeping vision and retinal anatomy stable.

For Rolling up features reduced off target binding and at clinically relevant doses does not inhibit tie to a critical pathway associated with vascular stability, which may result in an improved efficacy.

In a rodent model of retinal detachment Rowan have demonstrated neuro protection and because it blocks PDGF may also have anti fibrotic benefits.

George Elston: Before we begin our formal comments, I'll remind you that various remarks we will make today constitute forward looking statements for the purposes of the safe harbor provisions under the private security litigation reform act of 1995. These include statements about our future expectation, clinical developments and regulatory matters and timelines, the potential success of our products and product candidates, financial projections and our plans and prospects. Actual results may differ materially from those indicated by these forward looking statements as a result of various important factors, including those discussed in the risk factors section on our most recent annual report on form 10k, which is on file with the SEC and in other filings that we may make with the SEC in the future.

We were pleased to present preclinical and clinical data at multiple medical meetings that underscore the promising profile of <unk> 19 to one one.

One highlight was that last month's retina Society meeting, where a comparison of the anti Angiogenic profile of three Teekay is we're rolling it exit to nib and Sunitinib validated <unk> as a pan VEGF receptor inhibitor that effectively blocks the critical pathways of pathologic angiogenesis.

Importantly, the data showed that for rolling it is differentiated from the other TK ice tested at retinal disease.

Unlike sunitinib <unk> does not bind the melanin.

George Elston: Any forward looking statements represent our views as of today only while we may elect to update these forward looking statements at some point in the future, we specifically disglaim any obligation to do so, even if our views change. Therefore, you should not rely on these forward looking statements as representing our views as of any date subsequent to today.

Unlike acceptive for Roland is not expected to have a physiologic impact on normal tie to function.

As a reminder, the fully enrolled <unk> trial is evaluating <unk> 19, 1%, a 160 subjects with previously treated wet AMD.

<unk> therapy with a goal to maintain stable vision and retinal anatomy for the majority of wet AMD patients for six months or longer following a single injection of <unk> hundred one.

Jay Duker: I'll now turn the call over to Dr. J. Dukeer, President and Chief Executive Officer of Eyepoint Pharmaceuticals. Thank you, George.

This could represent a significant improvement compared to the current anti VEGF treatments that are dosed on average every two months in the United States under treat and extend protocol.

Jay Duker: Good morning, everyone, and thank you for joining us to discuss eye points, continued execution toward our milestones as we work to bring first in class therapeutics and delivery technologies to patients suffering from serious retinal diseases. In the third quarter, we both advanced and expanded our product pipeline with the announcement of positive mass safety data in our ongoing W2 and PVA phase 2 clinical trials for our lead product candidate, EYP-1901, which is the small molecule verolinib and our proprietary bio-wroteable DERSERT-E technology, as well as the unveiling of a new pre-clinical program, EYP-2301.

This lifetime of frequent treatment represents a tremendous burden for patients physicians and the health care system in general it.

<unk> 19, one has the potential to change this treatment paradigm into a treat to maintain model by providing sustained delivery of rolling in for approximately nine months following induction treatment with a large molecule antibody, Jeff like Anne Walker.

This may allow patients and practitioners the flexibility to reduce the number of visits without sacrificing visual outcomes.

The subjects in the <unk> trial were randomized to two treatment arms, approximately two milligrams or approximately three milligrams of <unk> thousand 19, O one or on label a flipper set that as a control.

Jay Duker: EYP-2301 delivers a promising tie-to activator, as you approach of Fifth, formerly known as AKB 977-8, formulated and derestured E to potentially improve outcomes in wet age-related macular degeneration, or wet A of D, and diabetic eye disease. It's an exciting time at EyePoint as our EYP 1901 clinical trials approach key data events with top-line phase two WO2 trial results anticipated in early December and Pavia results in Q2 of next year, and as we plan to initiate a third phase two trial and diabetic macular edema or DME in Q1 of 2024.

All subjects in the trial received three loading doses of a flipper set on day, one month, one and month to followed by dosing of <unk> thousand 19 to one or a sham injection 30 minutes after the last loading dose.

The FDA approval pathway for this program and the primary endpoint for <unk> is non inferiority in the change of best corrected visual acuity or CPA for each of the $19 one arms versus the <unk> control arm.

The lower limit of non inferiority margin is defined as minus four five letter loss by the FDA.

For perspective patients do not generally notice a change in vision until they lose fiber more letters, which is the equivalent of one line on an eye chart.

Jay Duker: I'll now review our recent program and corporate updates and give an overview of upcoming catalysts. Turning to our lead program, EYP 1901 is being advanced as a potentially paradigm-shifting treatment for patients suffering from VEDGEF mediated retinal diseases. EYP 1901 is delivered with a single, intravitural injection in the physician's office, similar to the current FDA approved anti-VEDGEF biologic treatments. EYP 1901 is immediately bioavailable, featuring an initial burst of drug followed by near-constant zero-order kinetic release for approximately nine months.

I'd like to share our perspective in terms of targeted outcomes for the non inferiority CBA as there are both numerical and statistical considerations for this outcome.

First a very successful outcome in <unk> would be to mirror. The phase <unk> results that showed an average of two five letter loss six months after <unk> 91, which is good.

Recall that <unk> was an all comers open label non randomized phase one trial.

Jay Duker: EYP 1901 delivers verolinum, a selective and patent-protected tyrosine-kindness inhibitor, formulated in a solid insert using our proprietary sustained release biodeurotable DIRASERT E technology. Verolinum brings a new mechanistic approach to the treatment of VEDGEF mediated retinal diseases by acting as a PAN VEDGEF receptor blocker, blocking all VEDGEF isophorms. We expect EYP 1901 with its new MOA and sustained drug delivery for up to nine months to meaningfully reduce treatment burden in the majority of wedding of patients while keeping vision and retinal anatomy stable.

Just on learnings from that phase one trial, we modified inclusion and exclusion criteria for the <unk> trial in an effort to exclude is that were not responding to standard of care therapy.

We presented mast patient demographic data last quarter that reflects the fact that we enrolled a more controlled patient population in <unk> and in the phase one trial.

Generally and outcome of minus three letters or better would be a very strong numerical outcome and possibly statistically non inferior even in this relatively small trial.

If the <unk> 90 to one arms match or better the minus one four letters difference versus the two milligram a flipper sub control, which was what was seen in the 16 week eight milligram eylea arm in the Pulsar trial. This would represent an outstanding outcome from a single injection of <unk>.

Jay Duker: Verolinum features reduced off-target binding, and at clinically relevant doses does not inhibit TIE 2, a critical pathway associated with vascular stability, which may result in an improved efficacy. In a rodent model of retinal detachment, verolinum demonstrated neuroprotection, and because it locks PDGEF may also have anti-fibrodic benefits. We were pleased to present preclinical and clinical data at multiple medical meetings that underscore the promising profile of EYP 1901. One highlight was that last month's retina society meeting were a comparison of the anti-antigenic profile of three TKI's, verolinum, exitinib, and pseudinib, validated verolinib as a PAN VEDGEF receptor inhibitor that effectively blocks the critical pathways of pathologic endogenesis.

<unk>.

In addition to stable BCA. It is critical that the <unk> 19, one continues to show a favorable safety profile consistent with the interim mass safety update through October one 2023 across all of the <unk> hundred one clinical trials as.

As of October 1st approximately 170 patients have received <unk> 19 O one with a minimum of four months follow up post injection from the ongoing phase II and <unk> II clinical trials and the completed <unk> phase one trial with no reported drug related ocular Sce's and no reported drug related to Sistema.

Sce's.

Can use to give us confidence in the results of this crucial endpoint.

Jay Duker: Importantly, the data showed that verolinib is differentiated from the other TKI's tested retinal disease. Unlike synitinib, verolinib does not bind to melanin, and unlike exitinib, verolinib is not expected to have a physiologic impact on normal TIE 2 function. As a reminder, the fully enrolled WO2 trial was evaluating EYP 1901 and 160 subjects with previously treated WET AMD as a maintenance therapy, with a goal to maintain stable vision and retinal anatomy for the majority of WET AMD patients for six months or longer following a single injection of EYP 1901.

Although change in best corrected visual acuity is the primary endpoint reduction in treatment burden will also be a critical secondary outcome to consider given the unmet need in this patient population for more durable therapies.

For a clinically meaningful outcome, we believe that one or both of <unk> 19 to one arms need to result in a reduction in treatment burden of a minimum of 50% or better for the six months following <unk> injection at week eight.

In addition, we also believe that 50% or greater of the <unk> 19, when treated eyes should be supplement free up to the week 32 visit along with a relatively stable anatomy as measured by OTT.

Jay Duker: This could represent a significant improvement compared to the current anti-vegetal treatments that are dozed on average every two months in the United States under a treatment extend protocol. This lifetime of frequent treatment represents a tremendous burden for patients, physicians, and the healthcare system in general. EYP-1901 is the potential to change this treatment paradigm into a treat to maintain model by providing sustained delivery of rural and for approximately nine months, following induction treatment with a large molecule, anti-vegetal-like-and-blocker.

Based on our market research and KOL interactions. These endpoints will be meaningful to retina specialists, who treat wet AMD patients.

We plan to host a virtual call, which we're now retinal specialists, Dr. David Boyer and Dr. David loudly on November 9th at eight a M. Eastern time to discuss their perspectives on the current treatment landscape and the <unk> outcome considerations that I just reviewed we.

Jay Duker: This may allow patients and practitioners the flexibility to reduce the number of visits without sacrificing visual outcomes. The subjects in the W-2 trial were randomized to two treatment arms, approximately two milligrams, or approximately three milligrams, of EYP-1901, or unlabeled a flibersept as a control. All subjects of the trial received three loading doses of a flibersept on day one, month one, and month two, followed by dosing of EYP-1901 or a sham injection 30 minutes after the last loading dose.

We hope that you will all join US for this informative presentation and Q&A and you can find the link to that call in the investor tab of our website.

Looking ahead to the potential phase III pivotal trials for <unk> hundred one as maintenance therapy in wet AMD. Our current plan is to initiate the first trial by the fourth quarter of 2024.

This initial trial will be largely in the U S and Canada, we hope to initiate a second pivotal trial. Several months later, the second phase III trial will be largely outside of the U S.

Jay Duker: The FDA approval pathway for this program and the primary endpoint for W-2 is non-inferiority in the change of best corrected visual acuity or BCVA for each of the 1901 arms versus the flibersept control arm. The lower limit of non-inferiority margin is defined as minus 4.5 letter loss by the FDA. For perspective, patients do not generally notice a change in vision until they lose five or more letters, which is the equivalent of one line on an eye chart.

The phase III <unk> trial of <unk> 91 was designed to mirror the anticipated design of the phase III trials based on our type C meeting with the FDA and other interactions with the agency.

The key differences are that the phase III trials will feature re dosing of <unk> hundred one every six months and the primary efficacy endpoint will be non inferior change in visual acuity to approximately one year instead of eight months as it is in <unk>.

Jay Duker: I'd like to share our perspective in terms of targeted outcomes for the non-inferiority BCVA as there are both numerical and statistical considerations for this outcome. First, a very successful outcome in W-2 would be to mirror the phase one W-O BCVA results that showed an average of 2.5 letter loss six months after EYP-1901 was injected. Recall that W-O was an all-comers open label non-randomized phase one trial. Based on learnings from that phase one trial, we modified inclusion and exclusion criteria for the W-O-2 trial in an effort to exclude eyes that were not responding to standard care therapy.

We expect to share more details about this trial in the coming months.

Now, let me turn to our second indication and PDR in June we reported that enrollment of the phase II via clinical trial was complete.

Here is a randomized controlled phase II trial evaluating <unk> as a potential nine months treatment for moderate to severe NPD are.

Similar to the <unk> two trial are Pavia trial saw significant investigator and patient interest during enrollment the trial enrolled 77 patients exceeding the 60 patient target patients who were randomly assigned to one of two doses of <unk> 19 to one approximately two milligrams for approximately three milligrams or to the control group that risk.

Jay Duker: We presented massed patient demographic data last quarter that reflects the fact that we enrolled a more controlled patient population in W-O-2 than in the phase one trial. Generally, an outcome of minus three letters or better would be a very strong numerical outcome and possibly statistically non-inferior, even in this relatively small trial. If the EYP-1901 match or better, the minus 1.4 letters difference versus the 2 milligram of flibrecept control, which was what was seen in the 16-week 8 milligram ILEA arm in the pulsar trial, this would represent an outstanding outcome from a single injection of EYP-1901.

<unk> a sham injection.

As in the wet AMD trials, you might be 19, no. One is delivered with a single integrator injection in the physician's office.

As a reminder, and PDR is a very common retinal disease that affects almost one third of diabetic adults over the age of 40 and its projected to impact over 14 million Americans by 2050.

And PTR blood vessels are weakened potentially leading to swelling of the macula, which is called diabetic macular edema or <unk> and May eventually result in abnormal blood vessel growth, which is called proliferative diabetic retinopathy or PDR.

Both DMA in PDR could ultimately result in severe visual loss is important to note that there remains a great unmet need for a safe efficacious at convenient treatment for NPR that proactively reduces the risk of progressing to a sight threatening complication over the long term.

Jay Duker: In addition to stable BCVA, it is critical that the EYP-1901 continues to show a favorable safety profile, consistent with the interim mass safety update through October 1, 2023, across all of the EYP-1901 clinical trial. As of October 1st, approximately 170 patients have received the YP1901 with a minimum of four months follow-up post-injection from the ongoing phase 2 pvf and WO2 clinical trials and the completed WOF1 trial with no reported drug-related ocular SAEs and no reported drug-related systemic SAEs.

Approximately 90% of patients with NPD are currently received no course of therapy apart from observation by their eye doctor until their disease progresses to dnb and or PDR.

Might be 19 in one in our phase II <unk> trial could potentially reduce the risk of progressing to these complications with a less intrusive treatment protocol.

Recently, we reported an interim analysis of mass safety data from the phase II via clinical trial, and then PDR, which showed that as of October one 2023, <unk> hundred one was well tolerated with no reported drug related ocular or drug related systemic sce's demonstrating <unk> thousand 19.

Jay Duker: This continues to give us confidence in the results of this crucial endpoint. Although change and best-corrected visual acuity is the primary endpoint, reduction in treatment burden will also be a critical secondary outcome to consider, giving the unmet need in this patient population for more durable therapies. For a clinically meaningful outcome, we believe that one or both YP1901 arms need to result in a reduction in treatment burden of a minimum of 50% or better for the six months following the YP1901 injection at week 8. In addition, we also believe that 50% or greater of the YP1901 treatment to eyes should be supplement-free up to the week 32 visit, along with a relatively stable anatomy as measured by OCT.

Excellent safety profile at NPD are for the first time.

Topline data from the <unk> trial remains on track for the second quarter of 2024.

As mentioned earlier, we plan to initiate a phase II trial evaluating <unk> in Dnb and the first quarter of 2020 for which we are calling the Verona trial.

We will share details of that trial at a future date, but the goal of the Verona trial was to gain experience with <unk> 19 in one in this potentially large indication.

In September we disclosed a new preclinical program called <unk> 301.

Jay Duker: Based on our market research and KOL interactions, these endpoints will be meaningful to retina specialist who treat wet AMD patients.

<unk> 301 is tied to agonists rasp prototype, formerly known as <unk> nine 778, which we have formulated to work endures search E.

Jay Duker: We plan to host a virtual call with renowned retinal specialist Dr. David Boyer and Dr. David Lally on November 9 at 8 a.m. Eastern Time to discuss their perspectives on the current treatment landscape and the WO2 outcome considerations that I just reviewed. We hope that you will all join us for this informative presentation in Q&A and you can find the link to that call in the Phase 3 Pivotal Trials for YP1901 as maintenance therapy in wet AMD.

This has the potential to provide interim vitriol sustained delivery over six months or longer to improve the treatment of wet AMD and diabetic eye disease pre.

Previous preclinical and clinical studies show that rest of prototype delivered subcutaneously demonstrated proof of concept in diabetic eye disease, and we believe that delivering <unk> 'twenty 301, and <unk> has the potential to offer new site saving treatment for patients with severe retinal disease either.

Jay Duker: Our current plan is to initiate the first trial by the fourth quarter of 2024. This initial trial will be largely in the U.S, and Canada. We hope to initiate a second Pivotal trial several months later. This second Phase 3 trial will be largely outside of the U.S.

Loan or in combination with antibody chefs.

Finally, we were delighted to announce that <unk> expanded its board of directors with the appointment of Stewart duty, a seasoned biopharmaceutical financial executive who brings more than 25 years of experience to the role. We also strengthened our executive leadership team with the promotion of our CFO George Elsdon to the additional role.

Jay Duker: The Phase 2 WO2 trial of YP1901 was designed to mirror the anticipated design of the Phase 3 trials based on our type C meeting with the FDA and other interactions with the agency. The key differences are that the Phase 3 trials will feature redosing of YP1901 every six months and the primary efficacy endpoint will be non-inferior change in visual acuity to approximately one year instead of eight months as it is in WO2. We expect to share more details about this trial in the coming months.

Executive Vice President.

George his wealth of experience financial acumen, and strategic guidance, it's been a tremendous asset to our <unk> team.

Behalf of the entire leadership team, we welcome Stuart and congratulate George and we are grateful for their valuable leadership at <unk> point as we continue to build value for our shareholders. During this active time in the Companys growth.

Jay Duker: Now let me turn to our second indication, NPDR. In June we reported that enrollment of the Phase 2 Pivotal Trials was complete. The VA is a randomized controlled Phase 2 trial evaluating YP1901 as a potential nine-month treatment for moderate to severe NPDR. Similar to the WO2 trial, our Pivotal saw significant investigator in patient interest during enrollment. The trial enrolled 77 patients succeeding the 60 patient target. Patients who are randomly assigned to one of two doses of YP1901, approximately two milligrams or approximately three milligrams, or to the control group that received a sham injection. As in the Wed AMD trials, UIP-1901 is delivered with a single interpreter injection in the physician's office.

I'd like to thank the entire <unk> team for an incredibly productive quarter and I will now turn the call over to George to review the financials George.

Thank you Jay as the financial results for the three months ended September 32023 were included in the press release.

Issued this morning, my comments today will be focused on a high level review for the quarter.

For the third quarter ended September 32023, total net revenue was $15 2 million compared to $10 million for the quarter ended September 32022.

Product revenue for the third quarter was <unk> 8 million compared to net product revenues for the third quarter ended September 32022 of $9 7 million consistent.

Jay Duker: As a reminder, NPDR is a very common retinal disease that affects almost one-third of diabetic adults over the age of 40, and it's projected to impact over 14 million Americans by 2050. The DMA and NPDR can ultimately result in severe visual loss. It's important to note that there remains a great unmet need for a safe, efficacious and convenient treatment for NPDR that proactively reduces the risk of progressing to a site-threatening complication over the long term.

Consistent with the exit from the commercial business. The decline in revenue resulted from the sale of boutique franchise in May 2023, along with the discontinuation of marketing activity for the <unk> franchise. This year due to the loss of pass through reimbursement by CMS effective one $1 23.

Net revenue from royalties and collaborations for the third quarter ended September 32023 totaled $14 4 million compared to $3 million in the corresponding period in 2022.

The increase was primarily due to a recognition of deferred revenue from the sale of Utica, which will be recognized over a two year period, which began in Q2 of this year.

Jay Duker: Approximately 90% of patients with NPDR currently received no course of therapy, apart from observation by their eye doctor, until their disease progresses to DMA and or PDR. UIP-1901 in our Phase II Pavilion could potentially reduce the risk of progressing to these complications, with a less intrusive treatment protocol. Recently, we reported an interim analysis of mass safety data from the Phase II Pavilion clinical trial in NPDR, which showed that as of October 1st, 2023, UIP-1901 was well-tolerated with no reported drug-related ocular or drug-related systemic SAEs. Demonstrating UIP-1901's excellent safety profile in NPDR for the first time. Top-line data from the PVA trial remains on track for the second quarter of 2024.

Operating expenses for the third quarter ended September 32023 totaled $29 6 million versus $28 4 million in the prior year period. This.

This increase was primarily driven by higher R&D spending on <unk> hundred one clinical trials, partially offset by lower sales and marketing expense.

Nonoperating expense net totaled $1 8 million and net loss was $12 6 million or <unk> 33 per share compared to a net loss of $18 4 million or <unk> 49 per share in the prior year period.

Cash and investments at September 32023 totaled $136 million compared to $144 6 million at December 31, 2022.

We expect the cash cash equivalents and investments on September 32023 will enable us to fund our current and planned operations into 2025 and.

Jay Duker: As mentioned earlier, we plan to initiate a Phase II trial evaluating UIP-1901 in DMA in the first quarter of 2024, which we are calling the Verona trial. We will share details of that trial at a future date. The goal of the Verona trial was to gain experience with UIP-1901 in this potentially large indication.

In conclusion, we are pleased with <unk> progress in the third quarter and year to date and are well capitalized to advance our product pipeline to key value inflection points I will now turn the call back over to Jay for closing remarks.

Thank you George.

We believe <unk> as a potentially paradigm shifting treatment for patients suffering from serious retinal diseases, providing unique benefits that may include delivery of a rolling it consistently over approximately nine months.

Jay Duker: In September, we disclosed a new preclinical program called UIP-2301. UIP-2301 is tied to Agnes, RASA-Protofib, formerly known as AKB-9778, which we have formulated to work endure a CERT-E. This has the potential to provide intra-vitriol-sustained delivery over six months or longer to improve the treatment of WEDAMD and diabetic eye disease. Previous preclinical and clinical studies show that RASA-Protofib delivered subcutaneously demonstrated proof of concept in diabetic eye disease. And we believe that delivering UIP-2301 intra-vitrially has the potential to offer new psych-saving treatment for patients with severe retinal disease, either alone or in combination with anti-VHS.

New mechanism of action to treat retinal disease beyond anti VEGF like an blockade.

The potential for neuro protection, and anti fibrosis, and a proven delivery technology with a positive safety profile.

I will close by recapping key upcoming catalysts, including top line data from our phase III <unk> clinical trial anticipated in early December.

The dosing of the first patient in the phase III <unk> clinical trial of <unk> 19 to <unk> and DMA in the first quarter of next year and top line data release from our phase II <unk> clinical trial in the second quarter of 2024.

Jay Duker: Finally, we were delighted to announce that eye-point expanded its board of directors with the appointment of Stewart-Duty, a seasoned biopharmaceutical financial executive who brings more than 25 years of experience to the role. We also strengthen our executive leadership team with a promotion of our CFO to urge Elston to the additional role of executive vice president. Judgment. George's wealth of experience, financial acumen and strategic guidance has been a tremendous asset to our eye point team.

This remains an incredibly exciting time for <unk> as we are well positioned to execute on our upcoming milestones and continue to transform the treatment landscape with innovative long term solutions to improve both the vision and the lives of patients with serious retinal diseases.

Thank you all very much for listening. This morning, I will now turn it over to the operator for questions.

Thank you.

Our first question comes from the line.

Jay Duker: On behalf of the entire leadership team, we welcome Stuart and congratulate George and we are grateful for their valuable leadership at eye point as we continue to build value for our shareholders during this active time in the company's growth. I'd like to thank the entire eye point team for an incredibly productive quarter and I will now turn the call over to George to review the financials.

Peter Your line is now open.

Good morning, Congrats on the progress thanks, very much for the call I have a couple of questions for you.

First one is.

I appreciate the transparency you got the bandwidth respect your CVA outcome scenario ranges for the <unk> II trial ahead of the data, but we've been constructed in accordance with Kols and can you elaborate on what the Kols feedback has been regarding what they need to see from a trial, perhaps preview of sorts of the upcoming Kols event and then.

George Elston: George? Thank you Jay. As the financial results for the three months ended September 30th, 2023 were included in the press release. Issued this morning, my comments today will be focused on a high level review for the quarter. For the third quarter ended September 30, 2023, total net revenue was 15.2 million compared to 10 million for the quarter ended September 30, 2022. Net product revenue for the third quarter was 0.8 million compared to net product revenues for the third quarter ended September 30, 2022 of 9.7 million.

The second question is.

Upon positive data can you talk about how quickly you would be able to start the phase III program and is it possible to get the topline data in accelerated fashion or should we think about being a more traditional wet AMD phase III program timeline.

Thanks, Tyler I appreciate the questions and your interest.

First of all with respect to the BCA ranges.

So there's really kind of three ways to look at this and the first way is what does the FDA want.

George Elston: Consistent with the exit from the commercial business, the decline in revenue resulted from the sale of the UT franchise in May 2023, along with the discontinuation of marketing activity for the DEXICU franchise this year due to the loss of pass through reimbursement by CMS effective 1-1-23. Net revenue from royalties and collaborations for the third quarter ended September 30, 2023, totaled 14.4 million compared to 0.3 million in the corresponding period in 2022.

And Thats pretty clear.

Not the non inferiority margins got to be minus four five letters you can't cross it with your confidence intervals.

And depending on your end of your study in your standard deviation you could come pretty close to $4 five and get a result, but the second part of what you asked is what does it what does the kols want.

And interestingly when you ask them and Im sure you have.

George Elston: The increase was primarily due to a recognition of deferred revenue from the sale of UTIC which will be recognized over a two year period which began in Q2 of this year. Operating expenses for the third quarter ended September 30, 2023, totaled 29.6 million versus 28.4 million in the prior year period. This increase was primarily driven by higher R&D spending on EYP 1901 clinical trials partially offset by lower sales and marketing expense.

They're generally fine with a good efficacy profile good safety profile as long as the numerical change is in the range of $3 to four letters.

Interesting that I think that they believe in general that that type of change in vision is not noticeable to the patient.

On the other hand.

We as a company look at it as a combination of both of those and so that kind of minus three range or better I think based on what we anticipate the standard deviation of the trial might be.

George Elston: Non-operating expense net totaled 1.8 million in net loss was 12.6 million or 33 cents per share compared to a net loss of 18.4 million or 49 cents per share in the prior year period. Cash and investments at September 30, 2023 totaled 136 million compared to 144.6 million at December 31, 2022. We expect the cash, cash equivalence, and investments on September 30, 2023 will enable us to fund our current and planned operations into 2025.

In a pivotal trial would likely be non inferior.

And meet the Kols expectations.

Of course, we don't know what the results are yet we will know a approximately a month, but there's reasons to believe that we could do considerably better than that.

Second question was on the.

On the start of the phase III with good to great data.

George Elston: In conclusion, we are pleased with I points progress in the third quarter and year to date and are well capitalized to advance our product pipeline to key value inflection points.

We believe we can start the first phase III trial in the second half of next year. It may be closer to the fourth quarter. When we haven't really zeroed in on that.

Jay Duker: I will now turn the call back over to Jay for closing remarks. Thank you, George. We believe EYP 1901 is a potentially paradigm shifting treatment for patients suffering from serious retinal diseases, providing unique benefits that may include delivery of a rollinib consistently over approximately 9 months. A new mechanism of action to treat retinal disease beyond anti-veg eff ligand blockade, the potential for neuroprotection and anti-fibrosis, and a proven delivery technology with a positive safety profile.

Suffice it to stay the company has been really focused on phase III for basically the last nine months and there is a lot to do to get ready and we continue to be on track for our goal to started in the second half of next year.

From an accelerated perspective.

Think the trouble with unmasking early is you penalize yourself with a higher end.

And.

Cost and speed is critical here and if our statistics suggest we can do the phase threes with relatively low ends I think it's best to get them done right and get them done as fast as opposed to be penalize for an early look.

Jay Duker: I will close by recapping key upcoming catalysts, including the top line data from our Phase 2-2 clinical trial anticipated in early December, the dosing of the first patient and the Phase 2 Verona clinical trial of EYP-1901 and DMA in the first quarter of next year, and top line data released from our Phase 2 pv of clinical trial in the second quarter of 2024. This remains an incredibly exciting time for EyePoint as we are well positioned to execute on our upcoming milestones and continue to transform the treatment landscape with innovative long-term solutions to improve both the vision and the lives of patients with serious retinal diseases.

Hope that was sufficient to anything else.

No that's clear thank you very much.

Thank you so much.

Question comes from the line of Kevin.

Your line is now.

Thank you for taking my question. So Jay you just mentioned that Youre focused on obviously delivering this data but also in the phase III. So my question to you is and it also has to do with the competitive set is how does the IEA reduction relates to the mechanism of <unk> I didn't let AMD and then can you maybe just talk.

About why you think it is necessary for patients.

Unknown Executive: Thank you all very much for listening this morning.

To do that induction than your competitors.

Operator: I will now turn it over to the operator for questions. This is our most recent report.

Our doing.

Superiority study with just a single dose escalate percept as a comparator.

Tyler Buren: Our first question comes from the line of Tyler Van Buren of PD Common. Your line is now open. Good morning, Graig Suvannavejh, thanks very much for the call. I have a couple of questions for you.

Love to get your thoughts there.

Those are two great questions. Let me start with the induction first of all from a scientific perspective, it's unclear. If the induction offers anything to the patients treated with <unk> hundred one we have pretty good preclinical data that shows that our.

Tyler Buren: First one is, you know, I appreciate how transparent you guys have been with respect to your PCVA outcome scenario ranges for the WO2 trial ahead of the data, but we're these constructed in accordance with KOLs, and can you elaborate on what the KOL feedback has been regarding what they need to see from the trial, perhaps the preview of source of the upcoming KOL event, and then the second question is upon positive data, can you talk about how quickly you would be able to start the phase three program, and is it possible to get the top line data in an accelerated fashion, or should we think of it being a more traditional wet AMD phase three program timeline? Thanks, Tyler.

Drug is bio available in a corridor of animals within minutes of injection and reaches therapeutic levels on ours.

On the other hand, we've set out from the beginning to use <unk> as a maintenance therapy for previously treated wet AMD patients.

The decision to do the re induction.

Is something that came up with our discussions with the FDA around the structure of the phase III pivotal trials.

Tyler Buren: Appreciate the questions in your interest. First of all, with respect to the BCVA ranges, so there's really kind of three ways to look at this. And the first way is what does the FDA want, and that's pretty clear, not the non-afferiority margins gotta be minus 4.5 letters, you can't cross it with your confidence intervals. And depending on your study and your standard deviation, you could come pretty close to 4.5 and get a result, but the second part of what you ask is what does the KOLs want?

We had our type C meeting the FDA was certainly agreeable to us using eylea as our control in the phase III and when we discussed on label Eylea.

Fda's response was.

Yes. After you re induce the patients you can go to every other month on label Eylea and the rationale was to patients you enroll in that trial may be under treated and therefore before you allow them to go to every other month, you've got to reintroduce them makes sense.

And then we had to re engage the FDA and said well.

Tyler Buren: And interestingly, when you ask them, I'm sure you have, they're generally fine with a good efficacy profile, a good safety profile, as long as the numerical change is in the range of three to four letters. It's interesting that I think that they believe in general that that type of change in vision is not noticeable to the patient. On the other hand, we as a company look at it as a combination of both of those, and so that kind of minus three range or better, I think based on what we anticipate the standard deviation of the trial might be, in a pivotal trial would likely be non-inferior and meet the KOL's expectations. Of course, we don't know what the results are yet, we'll know it in approximately a month, but there's reasons to believe that we could do considerably better than that.

If we're going to make an assumption that some of these sites are under treated in the real world, which we think is probably true wed like to reintroduce all of the patients in the study.

And they were agreeable to that.

What that did however, as you may be aware you can have a nine month efficacy endpoint in the wet AMD study.

But our nine months doesn't start ticking until after that.

Load of Eylea, so what it was.

Tradeoff here was we needed to do in our pivotal trial, the efficacy endpoint out approximately one year.

We thought that was a fair trade off to be able to level, the playing field and make sure that we worked.

Wowing relatively undertreated patients to flood the <unk> arms.

So it really isn't a scientific reason I would say, it's a regulatory reason and a derisking reason that we're reducing.

So that I think gets into the second question.

Why induction.

Again, I think I've covered that.

Jay Duker: Second question was on the, on the start of the phase three, with good to great data, we believe we can start the first phase three trial in the second half of next year, it may be closer to the fourth quarter, you know, we haven't really zeroed in on that. Suffice it to stay, the company has been really focused on phase three prep for basically the last nine months. And there's a lot to do to get ready, and we continue to be on track for our goal to start in the second half of next year.

Our decision to do this.

I think more typical non inferiority phase III is again it comes out of our discussions with the FDA and a derisking.

That this is the fastest and least risky pathway to FDA approval.

I remind you that remember we had a type C meeting with FDA laying out the phase III plans, which will inform phase III.

And so that's also a big driver of focus going into.

Jay Duker: From an accelerated perspective, I think the trouble with unmasking early is you penalize yourself with a higher end. And, you know, cost and speed is critical here. And if our statistics suggest we can do the phase threes with relatively low ends, I think it's best to get them done right and get them done fast as opposed to, you know, be penalized for an early low. I hope that was sufficient. Anything else?

The phase III next year.

Got it very helpful. Just one more question if I may could.

Could you talk about the dose response, there are two doses in this study.

So just curious what would you expect should we expect any dose response.

And then if let's say if there is no dose response, just curious like how you will decide on the dose to take forward. Thank you.

That's another great question, the Aten and.

We really don't know if there will be a dose response, because its certainly possible that our two milligram dose will work.

Unknown Executive: Nope, that's clear. Thank you very much. Thank you so much.

Yatin Suneja: Your next question comes from the line of the ad insuméa of Guggenheim, Guggenheim.

<unk> to shutdown the receptor for up to nine months and therefore any additional drug may not give you additional benefit.

Yatin Suneja: Thank you for taking my question. So, Jay, you just mentioned that you may be focused on obviously delivering these data, but also on the phase three. So, my question to you is, and it also has to do with the competitor is, you know, how does the ILEA induction relate to the mechanism of TKIs in WETMD? And then, can you maybe just talk about why you think it is necessary for patient to do that induction when your competitors are doing a superiority study with just a single dose of a full of percept at the competitor? They'll love to get your thoughts there. Thanks, Yotton. Those are two great questions.

So I would say we are as a company a little bit agnostic to that I mean, it's nice to show a dose response.

And if theres some validation to that understandably on the other hand, if both are two milligram dose in our three milligram dose work.

Great and they are essentially the same.

Would opt to go with the two milligram dose approximately in our pivotal trial against a lower dose most likely around one milligrams.

Jay Duker: Let me start with the induction. First of all, from a scientific perspective, it's unclear if the induction offers anything to the patients treated with you by P901. We have pretty good preclinical data that shows that our drug is bioavailable in the core of animals within minutes of injection. And reaches therapeutic levels in hours. On the other hand, we've set out from the beginning to use EYP901 as a maintenance therapy for previously treated WETMD patients.

What that would do a courses enable us if successful to have fewer inserts in the eye and lower Cogs.

Okay. Thank you so much.

Thank you. So much. Your next question comes from the line of Jennifer Kim of Cantor Fitzgerald. Your line is now open.

So we are taking my questions as to the first is just touching on the PCB a question Jay I think in your prepared remarks, you said at the CBA letter change difference.

Three letters are better it would be good and I think investors are generally in line with that the most pushback I've gotten is on minus three to minus four letter scenario I. Just I was curious to see if you have any thoughts on that scenario is it is the base case or the hope that it would be better than that and.

Jay Duker: The decision to do the re-induction is something that came up with our discussions with the FDA around the structure of the phase three pivotal trials. When we had our type C meeting, the FDA was certainly agreeable to us using ILEA as our control in the phase three. And when we discussed on-label ILEA, the FDA's response was, yes, after you re-induced the patients, you can go to every other month on-label ILEA. In the rationale was, the patients you enroll in that trial may be under-treated.

<unk>.

Similar to that.

The scenario, where you get a minus three letter difference what's that <unk> have to assume a standard deviation better than what we've seen with <unk>.

Pds.

Sure Great questions Jennifer Thanks.

So the best corrected visual acuity of three or less difference.

Really would be I think kind of a clear pathway in everybody's mind, if we can replicate that in the.

Jay Duker: And therefore, before you allow them to go to every other month, you've got to re-induce them. Houston. Made sense. And then we had to re-engage the FDA and said, well, if we're going to make an assumption that some of these eyes are under treated in the real world, which we think is probably true, we'd like to re-induce all the patients in the study. And they were agreeable to that. What that did, however, is you may be aware, you can have a nine-month efficacy endpoint in a wet AMD study, but our nine months doesn't start ticking until after the re-load of ILEA.

Pivotal trials minus.

Minus three to minus four is it kind of a theoretical range, where one could argue that with a minus let's say three and a half letter difference and a large enough and in a small enough standard deviation that that could be statistically non inferior.

But then youre getting into a point here where would it be commercially successful.

So while it would meet that first bar of FDA approval. It may not meet the second bar of what the Kols Swanton, perhaps as you say what the investment community you might want to see as a result.

Jay Duker: So what it was, the trade-off here was we needed to do in our pivotal trial the efficacy endpoint out approximately one year. We thought that was a fair trade-off to be able to level the playing field and make sure that we weren't allowing relatively under-treated patients to flood the UIP-1981 arms. So it really isn't a scientific reason. I'd say it's a regulatory reason and a de-risking reason that we're re-inducing.

So I would say again centering on the three letters or better I think that beats everybody's test for success here.

I'd remind everyone that we were minus two five letters in the phase one at.

At six months after the $19 one was injected.

Jay Duker: So that I think gets into the second question, you know, why induction? Again, I think I've covered that. The our decision to do this, you know, I think more typical non-inferiority phase three is, again, a comes out of our discussion through the FDA and a de-risking. We think that this is the fastest and least risky pathway to FDA approval. I remind you that remember we had a Type-C meeting with FDA laying out the phase two plans which would inform phase three. And so that's also a big driver of focus going into the phase three next year. All right, very helpful.

And one would expect and of course, we don't know this yet, but one would expect the eylea control arm to be relatively stable after below between.

<unk>.

Weeks, eight and week 32, and if it is and we can replicate minus two five again.

I think that that would be really an outstanding result.

So the words again base case.

Again, I think a lot of this depends on what the view of what the.

What we need to do to advance the drug into.

Pivotal trials and one could see with a very tight standard deviation that even minus three letters would be statistically significant. So you mentioned the PD PDF standard deviations and again, if you go back and look at the pivotal trials and wet AMD.

Jay Duker: Just one more question if I may. Could you talk about the dose response? There are two doses in this study. So just curious, what would you expect? Should we expect any dose response? Yeah, and you know, if let's say if there is no dose response, just curious like how you will decide on the dose to take forward. Thank you. Yep, that's another great question. And we really don't know if there will be a dose response because it's certainly possible that our two milligram dose will work efficiently to shut down the receptor for up to nine months.

Yes.

But I think basically every one since.

<unk> was approved was done on a non inferiority basis in treatment naive patients and generally had standard deviation to the change in visual acuity of around 12 12 letters, that's because they are treatment naive some eyes response on lifestyle.

<unk> phase III enrolled previously treated patients like we did but they limited the length of time to diagnosis to nine months prior.

Jay Duker: And therefore any additional drug may not give you additional benefit. So I would say we're as a company, a little bit agnostic to that. I mean, it's nice to show a dose response and there's some validation to that understandably. On the other hand, if both are two milligram dose and are three milligram dose work great and they're essentially the same, we would opt to go with the two milligram dose approximately in our pivotal trial against a lower dose, most likely around one milligrams. What that would do, of course, is enable us if successful to have fewer inserts in the eye and lower the cogs. Thank you so much.

So some of those eyes, we're still relatively early in their treatment and still perhaps being treat an extended they weren't at a stable kind of pace of their treat of their disease yet.

They had $7 one letter standard deviation.

So we have reasons to believe that because of our.

The enrollment of eyes that have the disease longer than nine months.

Suggesting maybe more stable, but our standard deviation could be lower than that.

That answer the question, yes, it does.

Good one.

One more.

Competitor received or announced that they received an agreement under their superiority trial design. This morning.

Net net it seems like good news for the overall space given that the post stress guidance world. We're in but I'm wondering if you have any takes on that.

Jennifer Kim: Your next question comes from the line of Jennifer Kim of Cajun Fitzgerald.

Well, yes, and again that was just announced this morning with no details, but at a high level. This is great news, it's great news for all of the Teekay <unk> companies because it shows that the FDA is willing to work with us to advance this new paradigm into the clinic.

Jennifer Kim: Your line is now open, for taking my questions. I have two. The first is just touching on the BCBA question. Jay, I think you're in your prepared remarks. You said a BCBA letter change difference of three letters or better would be good. And I think investors are generally aligned with that. The most pushback I've gotten is on the minus three to minus four letter scenario. So I was curious to see if you have any thoughts on that scenario.

Jennifer Kim: Is it is a base case or the hope that it would be better than that? And similar to that in this scenario, where you get a minus three letter difference, would that say have to assume a standard deviation better than what we've seen with say PDF?

Jay Duker: Sure, great questions, Jennifer. Thanks. So the best corrected visual acuity of three or less difference really would be I think kind of a clear pathway in everybody's mind if we can replicate that in the pivotal trials. Minus three to minus four is a kind of a theoretical range where one could argue that with a minus let's say three and a half letter difference in a large enough and in a small enough standard deviation that that could be statistically non-inferior.

Jay Duker: But then you're getting into a point here where would it be commercially successful? So while it would meet that first bar of FDA approval, it may not meet the second bar of what the KOLs want and perhaps as you say what the investment community might want to see as a result. So I would say again centering on the three letters or better, I think that beats everybody's test for success here. I remind everyone that we were minus 2.5 letters in the phase one at six months after the 1901 was injected.

And as we know it's great for the space.

When investors see that there is a clear pathway to approval then things are de risked from our perspective.

We're very comfortable with our phase II design.

And if we get good to great results at this point I think our phase III design, which the FDA has already seen and commented on.

And through our type C meeting.

I think thats still would represent.

The fastest lease risky way to get approval for our drug.

Again last comment about this though is once we are able to see the details of.

The Spa that Okta is received we will like any <unk>.

Company should do is take a look at our program and see if there's any learnings from what they're doing but I have to against state, we're very comfortable with our approach to the pivotal trials and pathway to approval.

Okay. That's helpful. Thanks for taking my question.

Thank you so much. Your next question comes from the line of choline kidney Essakane.

Now.

Your line is now open to ask your question.

Maybe we could go back to coating. After then excellent.

Alright.

Your next question comes from the line.

I will get to arena Chardan. Please go ahead.

Excellent.

Plus my name that lets call. Thank.

Jay Duker: And one would expect, and of course we don't notice yet, but one would expect the ILEA control arm to be relatively stable after the load between weeks eight and week 32. And if it is, and we can replicate minus 2.5 again, I think that that would be really an outstanding result. So the word again is you know base case and you know it's again I think a lot of this depends on what the view of what what we need to do to advance the drug into you know pivotal trials.

Thank you for taking the question must have a coupon of 301 wanted to ask for the rationale for.

For this.

Product and specifically how does it fit with $19 one strategy given that there could be some overlapping indications. Thank you.

Thanks, Daniel that's a great question.

2301 is based around a molecule that's been studied in two phase two.

By a company called <unk>.

Acquired their assets and their lead product <unk> 977, eight was delivered subcutaneously.

For diabetic macular edema and for diabetic retinopathy.

And it showed really promising anatomic results, although the visual results did not enable the company to really go forward into pivotal trials.

Jay Duker: And one could see with a very tight standard deviation that even minus three letters would be statistically significant. So you mentioned the PDS standard deviations. And again, if you go back and look at the pivotal trials and what AMD, I think basically everyone since ILEA was approved was done on an honor for your already basis and treatment eye patients. And generally had standard deviations to the change in visual acuity of around 12.

This drug activates tie too and by activating tie to stabilize.

Blood vessels, and you down regulate Andrew tweeting to branch too and you may be aware that <unk> is a bi specific that blocks veg F and blocks and two so that pathway of and two blockage is a validated and we believe.

Jay Duker: 12 letters. That's because their treatment I eat. Some eyes respond, some eyes don't. The PDS phase three enrolled previously treated patients like we did, but they limited the length of time to diagnosis to nine months prior. So some of those eyes were still relatively early in their treatment and still perhaps being treated extended. They weren't at a stable kind of pace of their treat of their disease yet. They had 7.1 letter standard deviation.

That.

<unk> 907, and eight now you might be 'twenty 301.

Jay Duker: So we have reasons to believe that because of our enrollment of eyes that had the disease longer than nine months, are with suggesting they'd be more stable, but our standard deviation could be lower than that. That's the question. Yeah, it does.

May be a better way to block that pathway by activating tied to.

Secondly, we can now deliver it sustained release so the bi specific molecules still require relatively frequent injections.

And we believe we can deliver.

At therapeutic levels for over six months.

With a single injection of <unk> 2301.

So how does it fit in well that remains to be seen.

I think that we could develop it and test it in a non inferiority fashion to get a label against the standard of care for either wet AMD or do you mean or both or we can choose to go for a superiority trial using it in conjunction with any anti VEGF.

Jay Duker: If I could, one more, your competitor received, our announced that they received an agreement under their superiority trial design this morning. Net net, this seems like good news for the overall space given the post draft guidance world we're in, but I'm wondering if you have any takes on that? Well, yeah. And again, that was just announced this morning with no details. But at a high level, this is great news. It's great news for all of the TKI companies because it shows that the FDA is willing to work with us to advance this new paradigm into the clinic.

That of course.

Would be perhaps riskier.

Because the antibody chefs are so effective.

So really high ceiling on the other hand, if one is successful with that approach.

You would likely have a multibillion dollar product because doctors would relish the opportunity to do even better than.

You bet, Jeff alone how would it fit into <unk> 91.

You can.

Highly speculative because we've got a long pathway to go with <unk> 301 shorter pathway with <unk> 90 to one but you could envision a day when both have approval.

Jay Duker: And as we know, it's great for the space. When investors see that there's a clear pathway to approval, then things are de-risk. From our perspective, we're very comfortable with our phase two design. And if we get good to great results, at this point, I think our phase three design, which the FDA has already seen and commented on, and through our type of meeting, I think that still would represent the fastest, least risky way to get approval for our drug.

As stand alone in this combo and one could do it one of each in a single injection.

Obviously that there is a long pathway to that in a lot of permutations that we're going to look at but in a nutshell. What we believe we can do with 'twenty 301 is.

Activate the tie to pathway secondarily inactivate answer to and to do it in a sustained release fashion with a derisked molecule.

Alright got it thank you.

Jay Duker: Again, last comment about this, though, is once we are able to see the details of the spot that the doctors received, we will, like any company should do, is take a look at our program and see if there's any learnings from what they're doing. But I have to, against state, we're very comfortable with our approach to the pivotal trials in pathway to approval. Okay, that's helpful. Thanks for taking my question. Thank you. Thank you so much.

Your next question comes from the line of John Kim of Jones trading.

<unk>.

Thank you for taking my questions.

Couple of quick ones, So I guess.

For the wet AMD program following the data to read out which would be requesting an end of phase II trial with the FDA to further phase III trial design.

Unknown Executive: Your next question comes from the line up for me.

That's our plan.

In fact.

We would plan currently on having both a clinical and a phase II in our CMC end of phase II to gain alignment in both those areas.

Unknown Executive: Here's the opherent. Your line is now open. Colleen, your line is now open. Can you ask your question? Maybe we could go back to Colleen after the next one. All right.

Okay got it and the potential timing on that.

I would say.

Daniil Gataulin: Your next question comes from the line of Dallin Gatlin of Tardin. Please go ahead.

Late in the first quarter of next year May bleed into early second quarter of next year, depending again, how soon we can get all the clinical tables from <unk> two in a format that we can submit.

Daniil Gataulin: I couldn't hear what was my name that was called. Yeah, thank you for taking the question. I have a good one on 2301. I wanted to ask for the rationale for this product and specifically how does it fit with 1901 strategy given that there could be some overlapping indications. Thank you. Thanks, Daniel. That's a great question. 2301 is based around the molecule that been studied into phase two by a company called ARPO.

Okay, great. Thank you.

Spending step here.

Okay got you.

And.

<unk> complement inhibitor collaboration.

Updates should it should be.

Are you expecting.

From that program in 2024.

Thanks for that question, Sean Good question and.

The answer is.

As we've kind of said before we're really excited about the collaboration we're really excited about the molecule.

Daniil Gataulin: We acquired their assets and their lead product, AKB 9778 was delivered subcutaneous. Wesley, for diabetic macular edema, and for diabetic retinopathy. And it showed really promising anatomic results, although the visual results did not enable the company to really go forward into the viral trials. This drug activates ty2, and by activating ty2, you stabilize blood vessels, and you down-regulate angel pleatinopathy or angel tube. Now you may be aware that the bismo is a bispecific, that blocks vetchf and blocks angel tube.

Getting complement inhibitors to last several months to therapeutic levels in the eyes of challenge.

If it wasn't a challenge you'd see them already.

However, we've made great progress.

And we remain optimistic that we will be able to sustained release of complement inhibitor, but until we have really are confident in our formulation and our ability to do this consistently we're not going to make any public statements around that so I would say that again, we're still working on it we have made great progress we have some real.

Great scientists working on this.

Daniil Gataulin: So that pathway of angel tube lockage is validated. And we believe that AKB 9778 now, EYP 2301, may be a better way to block that pathway by activating ty2. Secondly, we can now deliver it sustained release. So these bispecific molecules still require relatively frequent injections. And we believe we can deliver at therapeutic levels for over six months with a sync injection of 2301.

But it's not an easy task to accomplish.

Yes, Sean maybe I can add to that because if you look at how we our cadence on disclosure.

Just disclose 'twenty 301, this past quarter, because we've gotten that to a point, where it formulates and we're in a position.

To move it into those preclinical.

Programs and I think you should think the same for the complement space as well once we get that formulation that we know works and has the right window.

We will start talking about it a little more publicly on what that path looks like.

Jay Duker: So how does it fit in? Well, that remains to be seen. I think that we could develop it and test it in a non-inferiority fashion to get a label against the standard of care for either wet MD or DMA or both, or we could choose to go for a superiority trial using it in conjunction with an anti-vegetia. That, of course, would be perhaps riskier because the anti-vegetia just are so effective. It sets a really high ceiling. On the other hand, if one is successful without approach, you would likely have a multi-billion dollar product because doctors would relish the opportunity to do even better than anti-vegetia for long.

Okay got you. Thank you and last one from me is that I thought the cash runway into 2025.

Include potential pivotal III.

Phase III trials.

So now that they are just starting to second half.

Thanks for that question, Sean So our face I'm, sorry, our cash guidance into 2025.

Includes the ongoing phase twos.

<unk> planned phase.

In <unk>, which is the Verona trial, which will we expect to start in Q1, along with a significant amount of phase III prep.

To start to be in a position to start the trials sometime second half of next year. It does not include.

The the actual clinical trial costs for the pivotal <unk> and as we've talked previously that's something that we're going to look to a range of options to fund.

Jay Duker: How would it fit into EYP 1901? Well, you know, you can highly speculative because we've got a long pathway to go with 2301, shorter pathway, with, with, thank you, no one, but you could envision a day when both have approval as standalone and as combo. And one could do it one of each in a single injection. Obviously, that there's a long pathway to that and a lot of permutations that we're going to look at. But in the nutshell, what we believe we can do with 2301 is activate the tie-to pathway, secondarily inactivate, and to do it in a sustainably fashion with a de-risk molecule. All right, got it.

Unknown Executive: Thank you. So much.

Which includes potential equity raise we've got strong strategic partner interest and some other levers that we can pull and we'll be talking about that over the coming months on our plans to fund that really after the phase II results.

Okay. Thank you again for taking our question. Thank you.

Your next question comes from the line of Neel Genesee One company. Your line is now open.

Question and my question, you'll probably it will be focusing on the potential future phase III study.

First one is that.

One of your latest presentation you have.

Our fourth scenarios in terms of the phase three of different.

Shantyam: Your next question comes from the line of Shantyam off-chones.

Sean Kim: Reading, please go ahead. Thank you for taking my questions. Just a couple quick ones. I guess for the WIT AMD program, following the WIT AMD to read out, would you be requesting an end-of-phase patrol over the update to further guide to phase three trial design? That's our plan. In fact, we would plan currently on having both a clinical end-of-phase two and a CMC end-of-phase two to gain alignment in both those areas.

PC VA.

Outcomes.

Just curious based on that.

Our assumptions.

Right.

In terms of under each.

Darryl.

The phase III study size might be then I have a follow up.

Yes, youre talking about on the CVA measures.

Alright.

They're all the way to minus four.

Yes, if I may.

Actually were.

Our interpretation of the phase III outcomes of where they might land.

Sean Kim: Yes. Okay. And the potential timing of that meeting. Uh, I would say late in the first quarter of next year, may bleed into early second quarter of next year, depending again, how soon we can get all the clinical tables from W2 in a format that we can submit. Okay. Great. Thank you. We'll be waiting step here. Okay. Gotcha. Um, and what's the rally value complement inhibitor collaboration? Uh, what updates should it should be at the expecting from that program in 2024?

And what they might mean for those those outcomes without knowing the standard deviation of the change in visual acuity.

We can't predict the size of the trials, but.

You can run it into a statistics package and we've certainly done that if we are minus one letter worse than the <unk> control and the standard deviation is 7% or less we could do pivotal trials that might evolve as few as.

250 to 300 patients.

Sean Kim: Uh, thanks for that question. Sean, you know, that's a good question. And, uh, the answer is, as we've kind of said before, we're really excited about the collaboration. We're really excited about the molecule, uh, getting complement inhibitors to last several months at therapeutic levels in the eyes of challenge. Uh, if it wasn't a challenge, you'd see them already. Uh, however, we've been great progress. Uh, and we remain optimistic that we will be able to sustain, release a complement inhibitor, but until we have really our confidence and our formulation and our we're not going to make any public statements around that.

So it's fluid because we don't know those results yet.

But there is a second consideration I think for most of these trials that.

When youre doing treatment naive patients when the standard deviation is larger.

Companies end up doing 500, 600 700 patient trials.

But thats because not only the standard deviation because the FDA requires a certain number of patients for safety.

So the FDA requires that you submit in Europe able to submit.

With one year efficacy data as of your second trial, you don't need it to your safety to submit.

But at the one year you need to have 300 patients treated with your go to market dose or higher.

Sean Kim: So I would say that again, we're still working on it. We have made great progress. Uh, we have some really great scientists working on this, uh, but it's not an easy task to accomplish. Yeah. Sean, maybe I can add to that because if you, if you look at how we, you know, our cadence on disclosure, you know, we, we just disclosed 23 or 1 this past quarter because we've gotten it to a point where it formulates and we're in a position, uh, to move it into those preclinical, uh, programs.

Ultimately you need approximately 400 patients treated with your go to market dose or higher for safety.

That's another consideration for the end of the trial and that might.

Sean Kim: And I think you should think the same for the complement space as well. Once we get that formulation that we know works and has the right window, uh, we'll start talking about it a little more publicly on what that pathway looks like. Okay. Thank you.

Suggest that we would maybe not to a one to one to one randomization in the pivotal and have more patients in the higher dose to reach those safety measures knowing that the statistics would allow a smaller number as.

As I've said already our view is to do this as quickly as safely as derisked.

It is less expensive as possible and that's how we are going to view all the options in the pivotal trials.

Sean Kim: And last one from me is that I'll cash runway into 2025. Does that include potential 503, uh, base three trials in wet MD as well? Now that you're looking to start in second ask. Yeah. Thanks for that question, Sean. So our face, I'm sorry, our cash guidance into 2025 includes the ongoing phase two's. The plan phase in DME, which is the Verona trial, which we'll, we expect to start in Q1 along with a significant amount of phase three prep, uh, to start, to, to be in a position to start the trials.

Okay, Great. That's very very helpful and you mentioned earlier that the phase III also incorporate the recruitment.

Options of course.

Can you elaborate a little bit more.

So at least what you've proposed.

We came in.

Any details on that sure. Thanks, and we've been I think we've been very consistent from the start.

Even though we have in vivo and in vitro evidence that these <unk> 19, when inserts will release at therapeutic levels for approximately nine months, we've done enough Tox studies to show that even if we re inject earlier than that we are.

Sean Kim: Sometimes second half of next year, it does not include the, um, the actual clinical trial costs for the pivotals. And, you know, as we've talked previously, you know, that's something that we're going to look to a range of options to fund, uh, which includes potential equity rate raise. We've got strong strategic partner interest and some other levers that we can pull. And we'll be talking about that, you know, over the coming months on, you know, our plans to fund that really after the phase two results. Okay. Thank you again for taking a good question. Thank you. Thank you so much.

Very safe area for toxicity of rolling up and number of inserts. In fact, we have not found the maximally tolerated level of roll into the <unk>. So from a safety perspective, it's not a problem why did we choose six months I think it's simple that's what retina specialists want.

They want flexibility to dose drugs, when they want to dose them.

And while it's clear that some ice can go longer than six months remember in our pivotal in our phase one trial, rather we had a third of the eyes made it a year without supplement.

Unknown Executive: Your next question comes from the line of Yale-Generative Law and Company.

Unknown Executive: Your line is now open. I'm just curious, based on those assumptions, what might be your swap in terms under each scenario, what the three studies size might be, then I have a follow-up. Yeah, you're talking about on the BCVA measures. Right from 1.0 on the way to my full. Yeah. Yeah, if I may, that does actually were our interpretation of the phase two outcomes of where they might land and what they might mean for those outcomes.

We're going for the label of every six months, because we want to give the doctors flexibility to dose that often should they choose to.

Okay, Great. That's helpful and then maybe one more.

Regarding his thoughts.

From the competitors.

Money or is that something you guys also consider or it still depends.

Well, yes, again, I think I did address this earlier, but I'll reiterate.

We have what we believe is an agreement with the FDA.

I'm, writing that we have an acceptable protocol for our pivotal trials.

If that is the fastest lease risky way to proceed that's our plan and we've seen nothing at this point to alter that obviously its dependent on good to great data from <unk> II.

But there may be.

Learnings from other companies approach and we'll be studying that to see if there are any learnings for us so until the details are out.

Jay Duker: Without knowing the standard deviation of the change in visuality, we can't predict the size of the trials. But, you know, you could run it into a statistics package and we've certainly done that. If we're minus one letter worse than the ILEA control and the standard deviation is seven or less, we could do pivotal trials that might evolve as few as 250 to 300 patients. So, it's fluid because we don't know those results yet.

Really can't make any comment on that except to reiterate once more we are very comfortable with where our program is that right now.

Okay, great and congrats on the other.

And look forward in early December.

Thank you so much. Your next question comes from the line of E. Chen.

Manhattan.

Your line is now.

Thank you for taking my question so.

My question is by positioning <unk> as a maintenance therapy.

Jay Duker: But there's a second consideration, I think, for most of these trials that when you're doing treatment naive patients when the standard deviation is larger, companies end up doing 500, 600, you know, 700 patient trials. But that's because not only the standard deviation because the FDA requires a certain number of patients for safety. So, the FDA requires that you submit and you're able to submit with one year efficacy data of your second trial, you don't need to do your safety to submit.

So your competitors seems to target treatment.

Patient in their phase III trial.

Does that mean, you could potentially lose part of the market in the future.

Could you use 19 alone for.

For treatment naive patients as well thank you.

So.

If we get a label for maintenance therapy and the label includes.

Ill follow we use of 19, one after induction with.

Jay Duker: But at the one year, you need to have 300 patients treated with your go-to-market dose or higher. Ultimately, you need approximately 400 patients treated with your go-to-market dose or higher for safety. So, that's another consideration for the end of the trial and that might, you know, suggest that we would maybe not do a one-to-one randomization in the Pivotals and have more patients in the higher dose to reach those safety measures knowing that the statistics would allow a smaller number. As I've said already, you know, our view is to do this as quickly as safely as de-risk and as less expensive as possible. And that's how we're going to view all the options in the Pivotals.

Eylea or any anti VEGF, let's say hypothetically.

I think doctors, knowing the retina specialist community the way I would do I think doctors will try. It earlier then after three induction doses in some cases, if we're safe effective and tolerable I think the argument might be why not use it after a second induction or first deduction dose will it be used.

A solo therapy, initially I think data needs to be shown that it's affected that way.

So again the market share depends on a lot of things and.

Once again, one of the things, we just talked about was reinjection and.

And the hope and expectation is we would get a label for every six months reinjection.

Jay Duker: Okay, great. That's very, very helpful. And you mentioned earlier that the Phase III also incorporates the regimen options of course. Could you elaborate a little bit more in terms of at least what you proposed, the regimen, any details on that? Sure. Yeah. Thanks. And we've been, I think we've been very consistent from the start. Even though we have in vivo and in vitro evidence that these EYP-191 inserts will release a therapeutic levels for approximately nine months, we've done enough talks studies to show that even if we re-inject earlier than that, we're in a very safe area for toxicity of a rollinib and number of inserts.

The FDA it was clear that if we wanted to label for Reinjection, we needed to test reinjection in the pivotal trials and so I think that if that is the way our label reads. Eventually I think that will have an advantage also so it's hard to predict.

We admit that but once again, we are very comfortable with where our program is that in the approach that we're taking.

And the retina community that we've talked to I think.

Is in favor of the approach that we're taking and if we get that label I think retina specialists will figure it out.

Maybe if I can add to that just keep in mind. The vast majority of the market as previously treated patients and the fact that we are going to be able to re dose every six months is going to be meaningful on our label and.

Jay Duker: In fact, we have not found the maximally tolerated level of a rollinib and analyze. So from a safety perspective, it's not a problem. Why did we choose six months? I think it's simple. That's what retinus specials want. They want flexibility to dose drugs when they want to dose them. And while it's clear that some eyes can go longer than six months, remember in our phase one trial rather, we had a third of the eyes made it a year without supplement. We're going for the label of every six months because we want to give the doctor's flexibility to dose that often, should they choose to.

I think ultimately physicians will have the opportunity to use it sooner, but as we think about our approach in the market approach, we're addressing a very significant portion of a $10 billion plus market. So.

We're comfortable with our pathway.

And I could add one more George that was an excellent point you made about for every newly diagnosed patient a retina specialist probably has a dozen or more previously treated patients in their practice. So once again from a recruitment perspective and from speed to filling a trial. There is a lot more maintenance therapy patients out there than there is.

Newly diagnosed and Thats one of the many reasons why we've chosen this pathway speed to approval.

Jay Duker: Okay, great. That's helpful. And maybe just add one more that's regarding spots from the competitors news. Not this morning. Was that something you guys also consider, or it still depends? Well, well, yeah, like, again, I think I did address this earlier, but I'll reiterate, we have what we believe is an agreement with the FDA. That's in writing that we have an acceptable protocol for our pivotal trials. If that is the fastest least risky way to proceed, that's our plan.

Thank you.

Could we see choline is still on the line and wants to ask a question, yes, she responds that she's having issues.

All this morning, so she's won't find her later.

Great.

Alright, and we actually don't have any further questions in the queue at this time.

Yes.

Participating in today's conference. This does conclude the webcast program you may now disconnect everyone have great day.

Thanks, everybody.

Jay Duker: And we've seen nothing at this point all to that. Obviously, it's dependent on good to great data from W of two. But there may be learnings from other companies approach and we'll be studying that to see if there are any learnings for us. So until the details are out, I really can't make any comment on that except to reiterate once more, we are very comfortable with where our program is at right now.

Jay Duker: Okay, great. And congrats on the other progress and look forward in early December. Thank you so much.

Unknown Executive: Your next question comes from the line on each end of the day to be right company. Your line is now open. Thank you for taking my question. So my question is by positioning 1901 as a maintenance therapy. Well, your competitor sings to target treatment not even patient in their faith through trial. Does that mean you could potentially lose part of the market in the future? I mean, could you use 1901 for treatment not you patients as well?

Unknown Executive: Thank you. So if we get a label for maintenance therapy and the label includes follow the use of 1901 after induction with Ilya or any anti Vegev, let's say hypothetically. I think doctors knowing the retina specialist community the way I do I think doctors will try it earlier than after three induction doses in some cases. If we're safe, effective and tolerable, I think the argument might be why not use it after a second induction or first induction dose.

Unknown Executive: Will it be used as solo therapy initially? I think data needs to be shown that it's effective that way. So again, the market share depends on a lot of things and once again, one of the things we just talked about was re-injection and the hope in expectation is we would get a label for every six months re-injection. Action. The FDA was clear that if we wanted a label for re-injection, we needed to test re-injection in the pivotal trials.

Unknown Executive: And so I think that if that is the way our label reads eventually, I think that will have an advantage also. So it's hard to predict, I will certainly admit that, but once again, we are very comfortable with where our programs at and the approach that we're taking. And the retina community that we've talked to, I think, is in favor of the approach that we're taking. And if we get that label, I think retina specialists will figure it out.

Unknown Executive: Yeah, and maybe if I can add to that, just keep in mind the vast majority of the market is previously treated patients and the fact that we are going to be able to read those every six months is going to be meaningful on our label. And I think ultimately physicians will have the opportunity to use it sooner, but as we think about our approach and the market approach, we're addressing a very significant portion of a $10 billion plus market.

Unknown Executive: So we're comfortable with our pathway. And I could have one more church, you know, that was an excellent point you made about, you know, for every newly diagnosed patient, a rather specials probably has a dozen or more previously treated patients in their practice. So once again, from a recruitment perspective and from speed to filling a trial, there's a lot more maintenance therapy patients out there than there is newly diagnosed. And that's one of the many reasons why we've chosen this pathway.

Unknown Executive: Speed to approval. Thank you.

Unknown Executive: Is this could we see if Colleen is still on the line and wants to ask a question? Yeah, she responded she's having issues a number of all this morning, so she's will find her later.

Unknown Executive: All right.

Operator: And we actually don't have any further questions in the queue at this time. So the gentleman, thank you for participating in today's conference. This doesn't seem to be your webcam on your program. Give me now disconnect everyone have a great day. Thanks to everybody.