EyePoint Pharmaceuticals, Inc. Price & Performance (EYPT)

Thank you, and thank you all for joining us on today's conference call to discuss EyePoint's EyePoint fourth quarter and full year 2024 financial results and recent corporate With me today is Doctor. Jay Duker, President and Chief Executive Officer. Jay will begin with a review of recent corporate updates and discuss the ongoing clinical trials for DuraVu, I will close with commentary on the fourth quarter and full year 2024 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 corporate developments. A copy of the release can be found in the Investor Relations tab on the company website, www.eyepointpharma.com EyePoint. 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 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 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 of our most recent annual report on Form 10 ks which is on file with the SEC and in other filings that we have made or 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 Doctor. Jay Duker, President and Chief Executive Officer of EyePoint EyePoint. Thanks, George. Good morning, everyone, and thank you for joining us 2024 was a year of continued execution and exceptional results for EyePoint on all fronts. Bringing us closer to delivering on our goal of bringing life changing treatments to patients with severe retinal diseases. On today's call, we will review why we're the leader in ocular sustained drug delivery and how we are uniquely positioned to improve patients' lives with strong data in two potential multibillion dollar blockbuster indications. We've advanced our best in class therapy DuraVu into Phase three clinical trials in wet age related macular degeneration Yes. Wet AMD. And we've reported positive twenty four week Phase two results in diabetic macular edema or DME, supporting a second Phase III opportunity.

DuraVu is the only sustained delivery program with robust data for an investigational six month therapy in both of these indications. Highlighting how a differentiated TKI with a new mechanism of action may improve patient outcomes compared to the standard of care. I want to emphasize the safety of our DuraSert technology, beginning with the four products already approved by the FDA. And continuing with the strong safety data from the four clinical trials of bioerodible Duracert E. Consisting of over 190 patients treated with DuraVu. This superb safety profile coupled with the excellent efficacy data we saw in DABIO-two, The Largest Intravitreal Phase II Sustained Delivery Clinical Trial In Wet AMD to date, has driven significant patient and physician interest in our ongoing pivotal trials. With both of our Phase III wet AMD trials Lugano and Luchia surpassing enrollment expectations. I'm pleased to report that we are exceeding his historical enrollment rates of comparable wet AMD trials by a substantial margin. The Lugano trial is now well over fifty percent enrolled and the LUCIA trial is tracking ahead of schedule as well. We continue to expect completion of enrollment in both trials in the second half of 2025 with top line data anticipated in 2026.

The tried and true non inferiority trial design of Lugano and Luchia in wet AMD represents a clear pathway to regulatory approval should the results be positive.

In the sustained release space, we anticipate being the first investigational six month Intravitra wet AMD program to submit a new drug application or NDA allowing us to potentially reach patients first. Our patient centric trial design should enable a broad product label with an optimal dosing interval. Thereby providing physicians flexibility and allowing us to capture more of the market share. As part of our preparation for success, our commercial manufacturing facility in Northbridge, Massachusetts is now online with DuraVu registration batch manufacturing We recently reported positive efficacy safety and subgroup data from our Phase two VARONA clinical trial for DuraVu in DME. Varona met primary and key secondary endpoints firmly establishing DuraVu as the only sustained release TKI program with an active DME program. DME is currently a large market but has a significant need for sustained delivery options. I will discuss the VORONA data in more detail later in this call, but based on the compelling Phase two data we expect to hold an end of Phase two meeting with the FDA around pivotal trial design in the second quarter of this year. We remain in a solid financial position. We ended 2024 with a noteworthy balance sheet of $371,000,000 in cash and investments and no debt This was bolstered by a $161,000,000 oversubscribed follow on equity offering in the fourth quarter.

Turning to our science, DuraVu consists of vorlonib, which is a patent protected best in class tyrosine kinase inhibitor or TKI formulated in proprietary bioerodible DuraSert E DuraSert has been safely delivered to tens of thousands of eyes across four FDA approved products.

Meaning both patients and physicians are at exceptionally comfortable with this delivery system and its established safety record. Duraceart E uses a bioerodible matrix that allows for the sustained delivery of drug via zero order kinetics release for at least six months. Zero order kinetics means that the drug is delivered at a steady rate. So that small payloads can give an extended therapeutic effect with constant tissue exposure. In addition, DuraSert E allows for immediate bioavailability and by design prevents uncontrolled release of free drug floating in the eye. Virolinib is not another anti VEGF and DuraVu is not just another anti VEGF program. Virolinib is a potent and selective TKI that brings a new mechanistic [indiscernible] through intracellular blocking of all VEGF receptors. It therefore blocks all isoforms of VEGF including VEGF C and D. Varonab has demonstrated neuroprotection in a validated retinal detachment animal model and may have an anti fibrotic benefit as it blocks the PDGF receptor. At tissue exposure achieved with DuraVu, varolinib does not block TYT2. Blockage of the TYE2 receptor is associated with retinal vascular instability. DuraVu is packaged in a prefilled sterile syringe injector. It is administered by a standard intravitreal injection in the physician's office similar to the current standard of care anti VEGF biologic treatments and consistent with current retinal practice dynamics.

Unlike currently approved biologic and other sustained release programs in development, however, Dura VUE can be shipped and stored at ambient temperature. We have strong patent protection for DuraVu in both The United States and outside of The U. S. This allows us to protect our innovation and provides us flexibility with our strategic partnerships. In summary, with an excellent safety profile, a distinct mechanism of action, zero order kinetics that allows for sustained microdose delivery for at least months great patent protection and convenience for physicians we believe DuraVu is well positioned as an excellent treatment option for patients with VEGF mediated retinal diseases. [indiscernible] Time to first supplement versus control. DuraVu two point seven milligram demonstrated an early sustained and clinically meaningful improvement in best corrected visual acuity or BCVA with a gain of 7.1 letters compared to baseline. And a central subfield thickness or CST improvement of 75.9 microns on OCT measurement. This represents 74% more drying effect versus the Aflabora control Visual and anatomic gains were observed as early as week four. And were much more robust than those achieved by the offlibercept control eyes. Demonstrating the immediate bioavailability of DuraVu and its differentiated profile as a sustained release TKI.

Both Dura VUE treatment arm showed a favorable safety and tolerability profile with no DuraVu related ocular or systemic serious adverse events reported to date. Yesterday, we presented subgroup analyses from the Phase two VARONA clinical trial of the supplement pre patients through week twenty four. The data demonstrated that for those eyes that went twenty four weeks, with no supplementation, DuraVu two point seven milligram had significantly better improvement in BCVA and anatomic control compared to the FLIPRESS control group. BCVA improved 10.3 letters compared to baseline versus only three letters improvement for the Aflubicelp control group. DuraVu two point seven milligram also demonstrates 17 microns. Versus only 31 microns the inflibrocept control. This result confirms that the positive data from the Phase two VORONA trial were driven by DERAVU as an active agent continuously released over six months, and that the unsupplemented eyes had improved visual acuity of about two lines on the eye chart. The highly positive Phase two data supports our plans to engage in discussions with The U. S. And ex U. S. Regulatory agencies to solidify the plans around a pivotal program. As a company, we are highly focused on the successful completion of our Phase three wet AMD program for DuraVu.

In WetMD, our goal is to provide a product that maintains stable vision and retinal anatomy for the majority of wet AMD patients within every six month label. This could represent a significant improvement compared to the current anti VEGF treatments that are typically dosed on average every two months in The United States. And it may allow patients and practitioners the flexibility to reduce the number of visits, without sacrificing visual outcomes. As previously mentioned, enrollment is ongoing in both of our pivotal Phase III wet AMD trials, LUKANO and LUKIA with rapid enrollment rates that are exceeding our expectations, Enrollment completion in both trials is expected in the second half of 2025, both trials have received exceptional investigator and patient enthusiasm to date, driven by an established and familiar trial design. The two essentially identical non inferiority trials with six month redosing provide a clear and recognized pathway for global regulatory and commercial success. Positioning DuraVu to become a potential blockbuster franchise. To close, I'd like to thank the entire entire EyePoint team for an incredible year and a strong start to 2025. The dedication and execution capabilities demonstrated by our team to reach these milestones reflects the entire organization's commitment to improving patients' lives.

On that note, I'd also like to thank the patients and the clinical investigators for their participation in our ongoing trials. Without you all, the progress we've made advancing DIRVU would not be possible. With our compelling clinical pipeline representing billion dollar product opportunities, our best in class sustained ocular delivery [indiscernible] along with a strong balance sheet, we have further established our role as the leader in ocular drug delivery and are well on our way to bringing impactful therapies to patients suffering from serious diseases. I will now turn the call over to George to review the financials. [indiscernible] Thank you, Jay. As Jay noted, we ended 2024 with a very strong balance sheet driven by continued stewardship of our cash and an oversubscribed $161,000,000 follow on financing in October ending the year with $371,000,000 in cash and investments. As the financial results for the three months and full year ended 12/31/2024, 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 quarter ended 12/31/2024, total net revenue was $11,600,000 compared to $14,000,000 for the quarter ended 12/31/2023. Net product revenue for the quarter ended December 31, 2024 was $800,000 compared to net product revenue for the quarter ended 12/31/2023, of $700,000 We expect net product revenue to continue at immaterial levels as we will no longer be supplying YUTIQ to ANI Pharmaceuticals our U. S. Partner as of 05/31/2025.

This follows the non renewal of a supply agreement that accompanied the sale of UT commercialization rights to Alimiro Sciences ANI, in 2023. Consistent with our strategy, our forward manufacturing focus is on our DuraVu program to support clinical trials and NDA filing and future commercial launch. Net revenue from royalties and collaborations for the fourth quarter ended 12/31/2024 totaled $10,800,000 compared to $13,300,000 in the corresponding period in 2023. The decrease was primarily driven by lower recognition of deferred revenue Operating expenses for the quarter ended 12/31/2024 totaled $56,800,000 compared to $30,400,000 in the prior year period. This increase was primarily driven the two ongoing Phase three trials for DuraVu, Net non operating income totaled $3,900,000 and net loss was $41,400,000 or $0.64 per share. Compared to a net loss of $14,100,000 or $0.33 per share for the prior year period. Turning to the full year ended 12/31/2024, total net revenue was 43,300,000.0 compared to $46,000,000 for the year ended 12/31/2023. Net product revenue for the full year ended 12/31/2024 We was $3,200,000 compared to net product revenue for the full year ended 12/31/2023, of 14,200,000.0 This decrease was driven by the license of YUTIQ product rights, sold in May 2023 completing iPoint's exit from its commercial business, Net revenue from royalty and collaborations for the full year 12/31/2024 totaled 40,100,000.0 compared to 31,800,000.0 in the corresponding period in 2023.

The increase was primarily driven by full year recognition of deferred revenue in 2024 from the license of YUTIQ product rights versus a partial year in 2023. Operating expenses for the full year ended December 31, 2024 totaled $189,100,000 versus $121,100,000 in the prior year period. This increase was attributed primarily to a 26,600,000.0 increase in clinical trial costs related to the Phase three clinical trials of DuraVu dollars 28,000,000 of increased personnel costs across the organization, including $24,700,000 increase of non cash stock compensation, $16,700,000 in DuraVu nonclinical and license expense These increases were offset by $3,300,000 decrease in other sales and marketing expenses due to discontinuation of YUTIQ commercialization in 2023. Net non operating income totaled 15,100,000.0 and net loss was $130,900,000 dollars or $2.32 per share compared to a net loss of $70,800,000 or $1.82 per share for the prior year period. Cash, cash equivalents and investments in marketable securities on 12/31/2024 were totaled $371,000,000 compared to $331,000,000 as of 12/31/2023. We expect the cash and investments on 12/31/2024 will enable us to fund operations into 2027, beyond top line Phase three data for DuraVu in wet AMD expected in 2026, Accordingly, based on our solid cash position, we currently have no plans to access the equity capital markets this year.

In conclusion, we are incredibly pleased with EyePoint's progress in 2024 and are well capitalized to advance our DuraVu program through Phase three trials in wet AMD. I will now turn the call back over to Jay for closing remarks. Thank you, George. As we've discussed, EyePoint continues to be a story of a superior product strong execution and focused leadership the retinal disease space, We've accomplished our clinical milestones efficiently and aligned with our guidance and we plan to continue this in 2025 and beyond. Key upcoming catalysts include enrollment completion in the Phase three Lugano and Luchia clinical trials of DuraVu in wet AMD in the second half of twenty twenty five. Top line data for these Phase three trials in 2026 and an end of Phase two meeting with the U. S. FDA to discuss the first pivotal Phase III trial of DuraVu in DME. 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.

I will now turn the call over to the operator for questions. Thank you. Our first question is going to come from the line of Tessa Romero with JPMorgan. Your line is open. Please go ahead. Hi, Jay and team. Thank you for taking our questions this morning. For your wet AMD pivotal program, how many clinical sites have been activated across the trials of your overall target so far? I think you are at over 100 sites activated across the trials. As of our conference in January. And for LUTIA, can you remind us how many ex U. S. Sites do you have open and are you aiming to open? Thanks so much.

Good morning, Tess.

Thanks for your questions. I'd like to introduce our Chief Medical Officer, Ramiro Rivera, who's also on the call. Doctor. Oberto, do you want to answer those questions first of all about our wet AMD trials? The current sites open and blue ex U. S. Sites planned. Yes. Thanks Jay and good morning everybody. Thanks for the question Jess.

So we have most of the sites already activated in The U. S. The ones that are not activated yet are usually the ones that have more main process like academic centers that takes a little bit longer to be activated. But I think as we show with our enrollment numbers, we are very pleased with the progress of the studies and we have most of the sites already activated, especially the strong ones. In terms of ex U. S, we are planning to have between sixty and eighty sites per study. Which should be coming later this year.

Can you just clarify your numbers of active sites currently in each trial.

So we have approximately active about 60 sites per study.

Okay. Thanks so much.

Thank you.

And one moment as we move on to the next question. Our next question comes from the line of Yigal Notromovitz with Citigroup. Your line is open. Please go ahead.

Hi, Jay and team. Thank you for taking the questions. I just had one on the analysis you presented yesterday on the supplement free.

It was interesting that you got a very, very strong separation with the two point seven milligram versus flivircept. Though for the one point three, it's seems like it didn't separate as much as one may have expected. I'm just curious if you could comment on the trend there relative to what was observed with the overall population of the twenty six patients? Thanks.

Yes. Thanks, Yigal. Terrific question. And again, I think that evaluation of the subgroup analysis in particular the subgroup of the non supplemented patients really shows you how powerful DuraVu was in this DME population. So these were the eyes that made it the whole twenty four weeks. Without anything else other than DuraVu. [indiscernible] Our group and they improved over 10 letters and had 117 microns less fluid, which was significantly better than the unsupplemented eyes. In the control I think what we're seeing essentially is evidence dose response between the two point seven and the one point three doses And of course, the two point seven dose is what we're using in the current pivotal trials What we plan on using in the pivotal trials at DME and what our go to market dose is. But we interpreted with there are some individual variability within those numbers, but we think this represents a dose response. So, what it shows you is that when DuraVu works in this population, it works exceedingly well. And the supplement free rates that were achieved by the two point seven milligram dose We're not clouded by the fact that those supplement free eyes were slowly losing vision or slowly gating fluid, but didn't meet the criteria.

In fact, when you look at those curves, they are flat So these eyes that were supplement free were extremely well controlled. I will bring up the point too that the supplements in the two point seven group with one exception didn't really seem to change the vision or the fluid much, suggesting that we had reached perhaps a ceiling effect in most of these eyes. So yes, that analysis is very strong. And I think to try to explain the differences, I think again, it's dose response between the two doses with a little bit of individual variability there. Okay, thanks. And just one very quick one.

On the timing of the Phase 3s. Will there come a point perhaps later this year where you'd be able to provide a little bit more granularity on sort of which half of twenty twenty six we may expect the Phase three top line data?

The Phase three top line data, sure. I think we will be able to give you more granularity Certainly, as we approach last patient in the LUXHIA, I think that'll be obvious. So yes, we do expect [indiscernible] I expect early in the second half of the year to give you some more granularity around that.

Perfect. Thank you so much.

Thank you. And one moment as we move on to the next question. Our next question comes from the line of Yatin Suneja with Guggenheim. Your line is open. Please go ahead.

Hey, guys. Thank you for taking my question. I mean, now that the study is 50% enrolled, are you able to characterize the type of patients you are able to recruit right now? How they might be I know there are differences versus W2, but anything you can just comment on So that's one. The second one is on DME side. I mean, now that you have a little bit more time to analyze the data, could you maybe talk about the development plan, especially the Phase III, how you are thinking about what sort of a load we [indiscernible] Thanks, Jaat. First, the first question, about the patient population, I think at a high level, we have said that we're capping the previously treated patients at approximately 25%. And we have reached that cap in Lugano. So the majority of patients obviously at this point since we're over fifty percent enrolled [indiscernible] our treatment naive patients. But we don't expect in that trial to be enrolling any more previously treated patients. So that's really kind of the high level understanding of where we're at with the type of patients we've recruited. Beyond that, there's really been no kind of analysis done yet [indiscernible] we don't expect to be doing any analysis before this study [indiscernible] On any kind of other details around that.

With respect to the Phase three DME trial, we have a lot of options [indiscernible] I think probably Romero's the best person to give you a little bit more specifics, but the truth is we don't know yet exactly what we're going to do. We really need to get some important questions answered by the agency around this. But the top line here is the data was so robust I think we have a lot of options [indiscernible] [indiscernible] give us a pathway to approval. So, Romero, any more detail you want to add on that?

Yes. I think as you mentioned, Jade, the the data from the Phase two study does show immediate benefit on BCVA On day one, So that type of result give us flexibility while we think about designing the Phase three studies for DME.

The first option, of course, always going to be something similar to what we're doing for [indiscernible] Right? We have the loading dose which for DME in this case is five loading dose of aflibercept and then we would give to review. But again, based on the results from the Phase III study, I think we might have an opportunity to design a study that is more efficient meaning were dosed to review earlier. Do a study that could be a little bit shorter and overall have the results sooner. [indiscernible] One more question. This one is for George. Could you maybe help us model the R and D expense going forward at least in 2025? [indiscernible] Yatin, so remember, we did see that fairly meaningful increase in Q4.

And that was really related to initiation of both the Lugano and Luchia trials in the fourth quarter. I think that's probably a good barometer roll forward 2024. As we clarified yesterday and again today, we are laser focused on execution of those trials And that's going to be the focus for our burn on the R and D side in 2025.

Thank you. One moment as we move to the next question.

Our next question comes from the line of Cam Bischiarazzi with Jefferies. Your line is open. Please go ahead.

Good morning and team. Congratulations on the enrollment progress. While Lucia and Lugana remain the laser focused post marketing studies for Dura VUE long term? If so, what information would be valuable to glean from such studies and help further differentiate DIRUVIA in what AMD marketplace? Thank you so much.

Thanks, Kimbese, for that question. And obviously, we've already started to think about what other studies [indiscernible] enhance the value of DuraVu and WAYMD. In the one we've talked about, I think for a while, [indiscernible] is most obvious would approval to run the study in wet AMD of DuraVu against whatever the current industry leader for ligand blocker is at the point, whether it's high dose ILIA or VIBISMO. In the study, instead of the primary EyePoint, [indiscernible] change in visual acuity, the primary endpoint would be supplement free rate up to six months or percentage buys on supplemented or time to first supplement, that sort of thing. The obvious reason for doing that is we're going up against two milligram EYLEA in the pivotal trials, which is a regulatory requirement. And while two milligram EYLEA remains a very, very good treatment as a ligand blocker, with terrific short term efficacy The market seems to be moving [indiscernible] suspect high dose of the eventually. So it makes sense to prove our longevity against those two products. We think we would do very well. Against that, and obviously then give us some more strength in the marketing argument.

I can ask Romero any other thoughts you might have on [indiscernible] post approval studies that would be interesting and helpful.

Yes, I think we we are just learning about the effect of CTI in wet AMD And of course, the Phase three studies are laser focused on getting our regulatory approval. But as Jay mentioned, we're going to do studies comparing to other ligand block but also exploring additional benefits that AT a TKI inhibitor could have such as prevention of atrophy in this type of lesion d patients. So that's something that we're also going to be looking for as next question comes from the line of Jennifer Kim with Cantor Fitzgerald. Your line is open. Please go ahead. Hi. Thanks for taking my question and congrats on all the strong execution. Maybe first to start in DME.

You Give Us Some More Color On Your Plans To Meet With Both U. S. And US agencies next quarter, including what you're hoping to take away from both Should we expect an update by next quarter or would that come shortly after? And then understanding that when AMD takes center stage, what was sort of trigger a decision to advance the pivotal program? Is it contingent on sort of that accelerated pathway that Ramiro was talking about?

Thanks, Jennifer. Terrific questions as usual. So I'm going to let Romero give a little more details [indiscernible] what type of interaction we'd expect and hope for with the regulatory agencies Typically, what we've done in the past and I suspect what we'll do for this as well is after we get the written minutes, we would have a public announcement about [indiscernible] what our plans are and how they obviously sync with what the agencies have have told us. As for acceleration of DME, That again we do not at this point as a company want to put anything at risk with wet AMD. We really are delighted with how it's going. We want to continue to make sure that we have the resources within the company, both people resources and financial resources [indiscernible] have a strong cash runway after the wet AMD data And therefore, decisions about the structure of DME after regulatory meetings and the timing of DME is really going to be secondary to this first principle, which is make sure that Wet AMD is successful.

So over to Romero again, any color on how what we really hope to accomplish with the two few meeting with the agencies.

Yes. So we are planning to have a meeting both with the FDA as well as with the MA to ensure we get a regulatory feedback globally In the end of the day, the questions are going to be around the design of the study. So of course, I think we're going to propose something that as I mentioned before, would make a study efficient and then get feedback from the agencies if they agree with that. Approach.

Okay. And if I could ask one question on the wet AMD programs. Since you talked about the 60 sites per study roughly Should we think about I guess given the enrollment we seen with Lugano, should we think about LUCIA in the same way or is there sort of a split in high enrollers tapping into Lugano before they move into Lucia. I'm just trying to think through what the cadence looks like.

So The number of sites in Lugano at this point is slightly higher [indiscernible] We do have expect more LUCIA sites to come on over time. Remember, LUKIA started approximately, I think it was perhaps first patient in six, seven weeks after Lugano. So there's naturally going to be I wouldn't call a delay, but a little separation between the rise in the recruitment So what we're seeing though in recruitment rise in LUTCHIA is mirroring what we saw at the beginning of the Lugano trial.

So we are optimistic and confident that the of enrollment we saw in the the LUBNADA will be matched by LUCIA.

All right. That's helpful. Thanks guys. Thank you. One moment as we move on to the next question.

Our next question comes from the line of Greg Suvaanovitch with Mizuho Securities. Your line is open. Please go ahead.

Good morning. Thanks for taking my question. Congrats on the progress in the year and the quarter. I just wanted to ask a question about your Northbridge manufacturing facility, manufacturing obviously is something that we on the sales side don't get a lot of visibility into, but maybe can you talk about you are anticipating the manufacturing progress to continue and maybe some color on I guess, kind of the quality of the site that you've built out there and potentially anticipating any potential CMC issues, which obviously we always worry about, because we can't get visibility into that. Thanks.

Thanks, Greg. George, do you want to answer that question? Yeah, sure. Martin, great. How we did it and how it's going?

Yes, Greg, really great question and thanks for that because we've been out ahead of this for several years. I think just to remind the audience, we opened our Northbridge facility last fall, state of the art 41,000 square foot facility We're focused not just on clinical execution, but being ready for registration batches, pre approval and inspections and ultimately commercialization The team has really done a remarkable job getting that site up and running. And we will we really pivoted all Dura VUE manufacturing forward to that site. And the team has already started activities to get ready to start registration batches this year to support an NDA filing. The site was actually built to our specifications by the landlord, it didn't involve any cash investment. So it's really worked out incredibly well for us. And importantly, to your point, we've had FDA involved early in the design and execution of that site. And our quality team has had that in mind the entire way. So we're feeling really positive and really prepared as we get on the other side of data that we're going to have not just product for leak clinical, but also be able to support successful commercial launch with positive data.

If I may tell a little anecdote about the site too, which I think reflects the team that we have and how focused we are. I've obviously been out there many times and right before we were ready to have an official opening, I went out to inspect And I walked around the site, it's in the middle of the woods actually, it's a beautiful area. Walked around the site and there's a sidewalk all the way around The building, I went to the head of the building and I said, why did we put a sidewalk all the way around the building? And his response was, so when the FDA comes to inspect us if it's a rainy day, they will have a sidewalk to walk on. That is the type of foresight that the team has putting it together to make sure that this site will be up and running on time into both FDA and EMA specifications. And we expect from a commercial perspective to be able to supply the entire global supply for DuraVu from this site.

Thank you. One moment as we move on to the next question.

Our next question comes from the line of Colleen Cussey with Baird. Your line is open. Please go ahead. Great. Good morning. Thanks for taking our questions and congrats on all the progress.

We've seen with other retina studies talking about GA studies, a difference in results in ex U. S. Versus U. S. Sites. Can you speak to whether you'd expect a meaningful difference in the type of patients you're enrolling in Lugano and Luchia? Any differences in the standard deviation for patients and how that might impact the top line results?

Great question, Colleen. And I have the best person next to me to answer that [indiscernible] Doctor. Ribeiro, who of course was quite involved in one of the international GA studies. So, Romero, what do you think?

Yes. No, good question. And I think if we go back on the GAI, I think that was something that could be one of the hypothesis, but I'm not sure if it was truly confirmed that the geographical difference were one of the reasons for the difference in the results Regardless, we WestMD studies are much more mature than GA trials. Across the globe, right? So clinical sites have been doing these wet AMD studies for many, many years I think we nailed down our inclusion exclusion criteria accommodate a global study So I don't expect to see baseline characteristics being much different between The U. S. And ex U. S. Sites. Great. That's helpful. And one quick one if I can. On DME, does the FDA have the same non inferior non inferiority margin of minus 4.5 letters on the lower bound of the confidence interval as they do in wet AMD Roberto, do you know historically how the monetary margin has been calculated in DME? Yes. So for DME, of course, it's going to be part of our discussion with the FA EMA but I think if you look back up some of the previous studies, they tend to use four letters.

Instead of 4.5. But of course, it's going to be one of the questions we ask in our direction.

Great.

Thanks for taking our questions and congrats on the progress.

Thank you. One moment for our next question.

Next question comes from the line of Devanjana Chatterjee with Jones. Your line is open. Please go ahead.

Hi. Thanks for taking my question. So in terms of future market positioning, how would DuraVu's potential every six month label? Compared to Xpagli's potentials every six months, every twelve months label that Ocular has guided to.

Thanks for the question. I think an every six months label is what the physicians I think I think that's been made clear not only by us, but by quite a bit of market research. And of course, that's how we designed DuraVu to consistently deliver therapeutic levels of varrolinib for six months virtually everybody. So that we like our label, we like our study design, and we think the six month label will deliver that flex flexibility to patients and physicians to help tailor their individual treatment to maximize the vision maximize the drawing effect [indiscernible] minimizing the necessary visits and injections.

Thank you. And as a quick follow-up, the ratings has stacking up, you know, you could still be the first to market durable TKI. How would you use this lead time over Xtai's lead to capture the market.

Well, that's a really interesting question because it's quite broad. And of course, first to market, there is an advantage, as I think you all know, And we strongly believe that we are still in a position to be first market, especially driven by this great enrollment that we've talked about today. In saying that, we've had an early program [indiscernible] done here for the past two years on exactly how we are going to position DuraVu. And it is a shift in the market.

A true six month repeatable, safe, tolerable treatment for VEGF mediated diseases you could argue there really is nothing like that right now. So that the idea of how to get physicians comfortable with it is a process that we are doing right now and it will certainly accelerate internally as we get closer and closer to data, and closer to eventual launch.

So I think we could spend two hours on the details of what that might entail. But suffice it to say that just like we've been on the forefront [indiscernible] figuring out manufacture For commercial, we've been testing the market interviewing KOLs, talking to payers, talking to the business people the our retina groups in order to best position ourselves Thank you. Thanks for the insights.

Our next question is going to come from the line of Greg Harrison with Scotiabank. Your line is open. Please go ahead.

Hi, good morning. Thanks for taking the question.

Wanted to ask about your cash runway guidance and whether that includes assumptions for or what assumptions that includes for work in DNA DME and the earlier pipelines. And then separately, what is the current status of the RASA proteaship program and when could we see additional data there?

Thanks, Greg. I'm going to let George take both those questions.

Sure. So, Greg, our cash guidance is into 2027.

And I think as Jay said, we want to have meaningful cash on hand on the other side of the Phase three data. And so our guidance includes obviously everything associated with DuraVu and wet AMD. It includes our ongoing work in preparation internally for an eventual DME study, but not the study itself.

As far as razeprotafib goes, our pre clinical activities will continue there. Obviously, with our focus on wet AMD, that's gone to a lower priority, but it continues to move forward. As we look at some additional enabling studies to move that ultimately move that forward for an IND. But I would say that's on percolation mode. The organization remains laser focused on wet AMD execution this year and really conserving cash.

Great. Thanks. That's helpful.

Our next question comes from the line of Yael Jin with Leidlaw and Co. Your line is open. Please go ahead.

Great. Thanks for taking the question and congrats on all the progresses. Just two from us. The first one is that as you suggested you guys might be the first to market And given the ocular sort of mentioned a few days ago, they may have the top line result of result in the first quarter of twenty six Any read through from these two statements? And then I have a follow-up questions.

Sure. First to market, Of course, going to be highly dependent on that last patient in the second trial.

Whether the first trial which was not run concurrently reached out in the fourth quarter of this year, the first quarter of next year doesn't affect the last patient in the second trial and for us, of course, last patient in for the CHIA. Once again, as we look at the rate that we're we remain confident that Luchia will recruit as rapidly as Lugano is And therefore, we think that taken in total, we are confident we will be first to market.

Okay, great. That's very helpful. And maybe one follow-up here. Which is that a few days ago, you reported that the supplement free patients subgroup analysis I know the numbers are small, but just curious have you guys dissected the patient which do not need supplement versus those needs Any characteristic differences and be able to maybe apply to your current Phase three study?

Yes. Great question, Yale. I'm going to let Romero answer that.

Yes. No, good question. And I think you already mentioned the limitation of this study being a small study. So I think with these sample size it's a little bit hard to predict which patients are going to be supinator three.

Of course, once we have a larger database with the Phase three program, then that's something that we might be able to look at.

Okay, great. That's very helpful. Again, congrats on all the progress.

Thank you.

Our next question comes from the line of Yi Chen with H. Wainwright. Your line is open. Please go ahead.

Thank you for taking my question.

Could you talk about whether you currently have a plan to initiate a Phase three trial in DME at this point potentially late twenty twenty twenty five or 2026, if not? Do you plan to find a partner potentially moving this indication forward?

What would be the target enrollment suggested by VARONA results in a potential Phase three trial set.

All great questions, Yi. And I can say that we have currently no plans to initiate the pivotal trial in DME in 2025.

We believe that it will be a 2026 EyePoint.

At this point. We would certainly welcome a potential partner, but we're not going to partner an indication individually. A partnership that might include [indiscernible] program development in DME would have to be a much larger partnership or we really wouldn't be interested in it. So that's something that I think we would consider at the right time.

But as I said, it would have to be a much larger structured partnership than just DME. Ask for the [indiscernible] Again, I think maybe Romero, you might be able to answer that better about how we would approach the targets.

Yes. And I think we have a great benefit of having the wet in this study a lot of the learnings as well as the relationship we are building with the sites now. So we know that for DME's clinical sites, there would be very likely the same ones as we are using for wet AMD trials. So I think in terms of enrollment rates, we would also be optimistic for a DME trial.

Thank you. I am showing no further questions in the queue at this time. Ladies and gentlemen, thank you for participating in today's conference. This does conclude your program and you may now disconnect. Everyone, have a great day.