EyePoint Pharmaceuticals Inc (EYPT) 2024 Q4 法說會逐字稿

Good morning.

My name is Michelle, and I will be your conference operator today.

At this time, I would like to welcome everyone to the EyePoint fourth quarter and full year 2024 financial results and recent corporate development conference call.

(Operator Instructions).

Please be advised that this call is being recorded at the company's request.

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

Please go ahead, sir.

Thank you, and thank you all for joining us on today's conference call to discuss EyePoint's Fourth Quarter and Full Year 2024 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 clinical trials for DURAVYU, 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.

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 time lines, 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 10K, 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 Dr. Jay Duker, President and Chief Executive Officer of 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 are 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, DURAVYU into Phase 3, clinical trials in wet age-related macular degeneration or wet AMD.

And we've reported positive 24-week Phase 2, results in diabetic macular edema, or DME, and supporting a second Phase 3, opportunity.

DURAVYU is the only sustained delivery program with robust data for an investigational 6-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 bio-erodible Durasert E consisting of over 190 patients treated with DURAVYU.

This superb safety profile, coupled with the excellent efficacy data we saw in DAVIO2 the largest intravitreal Phase 2, 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 3, wet AMD trials, LUGANO and LUCIA surpassing enrollment expectations.

I'm pleased to report that we are exceeding historical enrollment rates of comparable wet AMD trials by a substantial margin.

The LUGANO trial is now well over 50% 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 LUCIA and 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 6-month intravitreal 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 DURAVYU registration batch manufacturing underway to support an NDA filing.

We recently reported positive efficacy, safety and sub-group data from our Phase 2, VERONA clinical trial for DURAVYU in DME.

VERONA met primary and key secondary end points firmly establishing DURAVYU as the only sustained-release TKI program with an active DME program.

DME is currently a large market that has a significant need for sustained delivery options.

I will discuss the VERONA data in more detail later in this call.

But based on the compelling Phase 2, data, we expect to hold an end of Phase 2, 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 million in cash and investments and no debt.

This was bolstered by a $161 million oversubscribed follow-on equity offering in the fourth quarter.

Turning to our science.

DURAVYU consists of Vorolanib, 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 exceptionally comfortable with this delivery system and its established safety record.

Durasert E uses a bioerodable matrix that allows for the sustained delivery of drug via zero order kinetic release for at least 6 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 bio-availability and by design prevents uncontrolled release of free drug floating in the eye.

Vorolanib is not another anti-VEGF and DURAVYU is not just another anti-VEGF program.

Vorolanib is a potent and selective TKI that brings a new mechanistic approach to the treatment of VEGF-mediated retinal diseases through intracellular blocking of all VEGF receptors.

It therefore blocks all isoforms of VEGF, including VEGF-C and VEGF-D.

Vorolanib has demonstrated neuroprotection in a validated retinal detachment animal model and may have an antifibrotic benefit as it blocks the PDGF receptor.

A tissue exposure achieved with DURAVYU, vorolanib does not block type two.

Blockage of the type two receptor is associated with retinal vascular instability.

DURAVYU 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 biologics and other sustained-release programs in development, however, DURAVYU can be shipped and stored at ambient temperature.

We have strong patent protection for DURAVYU in both the United States and outside of the US.

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 6 months, great patent protection and convenience for physicians, we believe DURAVYU is well positioned as an excellent treatment option for patients with VEGF-mediated retinal diseases.

Turning to the Phase 2, VERONA clinical trial in DME.

We recently announced positive 24-week safety and efficacy data for DURAVYU with both DURAVYU arms meeting the primary end point of longer time to first supplement versus control.

DURAVYU 2.7 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 aflibercept control. visual and anatomic gains were observed as early as week 4 and and we're much more robust than those achieved by the aflibercept control eyes, demonstrating the immediate bio-availability of DURAVYU and its differentiated profile as a sustained-release TKI.

Both DURAVYU treatment arm showed a favorable safety and tolerability profile with no DURAVYU related ocular or systemic serious adverse events reported to date.

Yesterday, we presented sub-group analyses from the Phase 2 VERONA clinical trial of the supplement free patients through week 24.

The data demonstrated that for those eyes that went 24 weeks with no supplementation DURAVYU 2.7 milligrams had a significantly better improvement in BCVA and anatomic control compared to the aflibercept control group.

BCVA improved 10.3 letters compared to baseline versus only three letters improvement for the aflibercept control group.

DURAVYU 2.7 milligram also demonstrated concomitant structural improvement with CST improvement of 117 microns versus only 31 microns for the aflibercept control.

This result confirms that the positive data from the Phase 2 VERONA trial were driven by DURAVYU as an active agent continuously released over 6 months and that the unsupplemented eyes had improved visual acuity of about two lines on the eye chart.

The highly positive Phase 2, data supports our plans to engage in discussions with the US and ex-US regulatory agencies to solidify the plans around a pivotal program.

As a company, we are highly focused on the successful completion of our Phase 3, wet AMD program for DURAVYU.

In wet AMD, our goal is to provide a product that maintains stable vision at retinal anatomy for the majority of wet AMD patients within every 6-month label.

This could represent a significant improvement compared to the current anti-VEGF treatments that are typically dosed on average every 2 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 3, wet AMD trials, LUGANO and LUCIA, 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 noninferiority trials with 6-month redosing provide a clear and recognized pathway for global regulatory and commercial success, positioning to review to become a potential blockbuster franchise.

To close, I'd like to thank the 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 DURAVYU would not be possible.

With our compelling clinical pipeline representing multibillion dollar product opportunities, our best-in-class sustained ocular delivery Durasert E technology, along with a strong balance sheet, we have further established our role as the leader in sustained ocular drug delivery and are well on our way to bringing impactful therapies to patients suffering from serious retinal diseases.

I will now turn the call over to George to review the financials.

George?

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 million follow-on financing in October, ending the year with $371 million in cash and investments.

As the financial results for the 3 months and full year ended December 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 December 31, 2024, total net revenue was $11.6 million compared to $14 million for the quarter ended December 31, 2023.

The Net product revenue for the quarter ended December 31, 2024, was $0.8 million compared to net product revenue for the quarter ended December 31, 2023, of $0.7 million.

We expect net product revenue to continue at immaterial levels as we will no longer be supplying YUTIQ to ANI Pharmaceuticals, our US partner as of May 31, 2025.

This follows the nonrenewal of a supply agreement that accompanied the sale of YUTIQ commercialization rights to Alimera Sciences, now ANI in 2023.

Consistent with our strategy, our forward manufacturing focus is on our review program to support clinical trials and NDA filing and future commercial launch.

Net revenue from royalties and collaborations for the fourth quarter ended December 31, 2024, totaled $10.8 million compared to $13.3 million in the corresponding period in 2023.

The decrease was primarily driven by lower recognition of deferred revenue from the license of YUTIQ product rights.

Operating expenses for the quarter ended December 31, 2024, totaled $56.8 million compared to $30.4 million in the prior year period.

This increase was primarily driven by the two ongoing Phase 3 trials for DURAVYU.

Net nonoperating income totaled $3.9 million and net loss was $41.4 million or $0.64 per share, compared to a net loss of $14.1 million or $0.33 per share for the prior year period.

Turning to the full year ended December 31, 2024.

Total net revenue was $43.3 million compared to $46 million for the year ended December 31, 2023.

Net product revenue for the full year ended December 31, 2024, was $3.2 million compared to net product revenues for the full year ended December 31, 2023, of $14.2 million.

This decrease was driven by the license of YUTIQ product rights sold in May 2023, completing EyePoint's exit from its commercial business.

Net revenue from royalty and collaborations for the full year ended December 31, 2024, totaled $40.1 million compared to $31.8 million 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 $189.1 million versus $121.1 million in the prior year period.

This increase was attributed primarily to a $26.6 million increase in clinical trial costs related to the Phase 3 clinical trials of DURAVYU, $28 million of increased personnel costs across the organization, including $24.7 million increase of non-cash stock compensation, $16.7 million in DURAVYU non-clinical and license expense, these increases were offset by a $3.3 million decrease in other sales and marketing expenses due to discontinuation of YUTIQ commercialization in 2023.

Net nonoperating income totaled $15.1 million, and net loss was $130.9 million or $2.32 per share compared to a net loss of $70.8 million or $1.82 per share for the prior year period.

Cash, cash equivalents and investments in marketable securities on December 31, 2024, totaled $371 million compared to $331 million as of December 31, 2023.

We expect the cash and investments on December 31, 2024, will enable us to fund operations into 2027 and beyond top line Phase 3, data for DURAVYU and 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 DURAVYU program through Phase 3 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 in 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 3 LUGANO and LUCIA clinical trials of DURAVYU and wet AMD in the second half of 2025.

Top line data for these Phase 3 trials in 2026 and an end of Phase 2 meeting with the US FDA to discuss the first pivotal Phase 3 trial of DURAVYU 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

(Operator Instructions).

Tessa Romero, JPMorgan.

Hi Jay and team and 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 were at over 100 sites activated across the trials, as of our conference in January.

And for LUCIA, can you remind us how many US sites do have open?

Or are you aiming to open?

Good morning, Tess.

Thanks for your questions.

I'd like to introduce our Chief Medical Officer, Ramiro Ribeiro, who is also on the call.

Dr. Ribeiro, do you want to answer those questions, first of all, about our wet MD trials, the current sites open and Blue ex US sites planned.

Yeah.

Thanks, Jay.

Thanks for the question, Tess.

So we have most of the sites already activated in the US The ones that are not activated yet are usually the words that have more line 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 US, we are planning to have between 60 and 80 sites per study, which should be coming later this year.

Thank you.

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

So we have approximately active about 60 sites per study.

Yigal Nochomovitz, Citigroup.

Yeah, hi Jay and team.

Thank you for taking the questions.

I just had one on the analysis you presented yesterday in the supplement.

It was interesting that you got a very, very strong separation with the 2.7 milligram versus aflibercept, though for the 1.3 , it seems like it didn't separate as much as one may have expected.

I was just curious if you could comment on the trend there.

Relative to what was observed with the overall population of the 26 patients.

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 DURAVYU was in this DME population.

So these were the eyes that made it the whole 24 weeks without anything else other than to review in 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 of dose response between the 2.7 and the 1.3 doses.

And of course, the 2.7 dose is what we're using in the current pivotal trials, what we plan on using in the pivotal trials in and what our go-to-market dose is.

But I -- we interpret it with -- there is some individual variability within those numbers, but we think this represents a dose response.

So what it shows you is that when DURAVYU works in this population, it works exceedingly well.

And the supplement free rates that were achieved by the 2.7 milligram dose, were not clouded by the fact that those supplementary eyes were slowly losing vision or slowly gaining fluid, but didn't meet the criteria.

In fact, when you look at those curves, they are flat.

So these eyes that were supplementary were extremely well controlled.

I will bring up the point, too, that the supplements in the 2.7 group with one exception didn't really seem to change the vision or the fluid much suggesting that we have 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 a 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 3.

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 2026, we may expect the Phase 3 top line data.

The Phase 3 top line data, sure.

I think we will be able to give you more granularity certainly as we approach last patient in LUCIA.

I think that will be obvious.

So yes, we do expect sometime, I expect early second half of the year to give you some more granularity around that.

Yatin Suneja, Guggenheim.

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 the 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 3, how you are thinking about what sort of a load we should expect from standard of care.

Yeah, thank you.

Thanks, Yatin.

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 and we have reached that cap in LUGANO.

So the majority of patients, obviously, at this point since we're over 50% enrolled, are 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.

And we don't expect to be doing any analysis before the studies are done on any kind of other details around that.

With respect to the Phase 3, DME trial, we have a lot of options here.

I think probably Ramiro is 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 that would give us a pathway to approval.

So Ramiro, any more detail you want to add on that?

Yeah.

I think as you mentioned, Jay, the the data from the Phase 2 study does show immediate benefit on the CVA on day 1.

So that type of results give us flexibility while we think about designing the Phase 3 studies for DME.

The first option, of course, is always going to be something similar to what we're doing for wet AMD, 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 3 study, I think we might have an opportunity to design a study that is more efficient, meaning we would dose to review earlier, do a study that could be a little bit shorter and overall, have the results sooner.

That helpful.

One more question.

This one is for George.

Could you maybe help us model the R&D expense going forward at least in 2025?

Yeah, Yatin.

So remember, you did see that a fairly meaningful increase in Q4, and that was really related to the initiation of both the LUGANO and LUCIA trials in the fourth quarter.

I think that's probably a good barometer of how you 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&D side.

Kambiz Yazdi, Jefferies.

Morning and team.

Congratulations on the enrollment progress.

While LUCIA and LUGANO remain the laser-focused near term, I was wondering if you've considered any opportunities to conduct post-marketing studies for DURAVYU long term?

If so, what information would be valuable to glean from such studies and help further differentiate DURAVYU and wet AMD marketplace?

Thank you so much.

Thanks Kambiz for that question.

And obviously, we've already started to think about what other studies might enhance the value of DURAVYU and wet AMD.

And the one we've talked about, I think, for a while, that is most obvious would post approval to run the study in wet AMD of DURAVYU against whatever the current industry leader for ligand blocker is at the point, whether it's high-dose (inaudible) or VABYSMO.

In the study, instead of the primary end point being change in visual acuity, the primary endpoint would be supplement free rate up to 6 months or percentage of eyes on supplemented or time to first supplement that sort of thing.

The obvious reason for doing that is we're going up against 2-milligram Eylea in the pivotal trials, which is a regulatory requirement.

And while 2-milligram Eylea remains a very, very good treatment as a ligand blocker with terrific short-term efficacy.

The market seems to be moving into VABYSMO and suspect high dose Elyea 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 Ramiro, any other thoughts you might have on post-approval studies that would be interesting and helpful.

Yeah.

I think we are just learning about the effect of TKI in AMD.

And of course, the Phase 3, studies are laser focused on gaining our regulatory approval.

But as Jay mentioned, we're going to do studies compared to all the ligand blockers.

But also exploring additional benefits that TK inhibitor could have such as prevention of atrophy in these type of wet AMD patients.

So that's something that we're also going to be looking for as a post-market study.

Jennifer Kim, Cantor Fitzgerald.

Hi, thanks for taking my question and congrats on all the strong execution.

Maybe first to start in DME.

Can you give a bit more color on your plans to meet with both US and ex 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 would 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 Ramiro give a little more details around 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 what the what our plans are and how they obviously sync with what the agencies 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 to 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 Ramiro again, any color on how -- what we really hope to accomplish with the 2Q meeting with the agencies.

Yeah.

So we are planning to have a meeting both with the FDA as well as with EMA to ensure we gather regulatory feedback globally.

At 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 six sites per study roughly.

Should we think about -- I guess, given the enrollment we've 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 -- the number of sites in LUGANO at this point is slightly higher than LUCIA.

We do have -- expect more LUCIA sites to come on over time.

Remember, LUCIA started approximately, I think it was perhaps first patient in 6-, 7-weeks after LUGANO.

So there's naturally going to be -- I wouldn't call it delay, but a little separation between the rise in the recruitment.

So what we're seeing though in recruitment rise in LUCIA is mirroring what we saw at the beginning of the LUGANO trial.

So we are optimistic and confident that the type of enrollment we saw in the LUGANO will be managed by LUCIA.

Graig Suvannavejh, Mizuho Securities.

Good morning.

Thanks for taking my question.

Congrats on the progress in the year in the quarter.

I just wanted to ask a question about your Northbridge manufacturing facility, manufacturing, obviously, is something that we on the cell I don't get a lot of visibility into, but maybe can you talk about how 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 anticipate any potential CMC issues, which, obviously, we always worry about because we can't get visibility to that.

Thanks.

Sure.

Thanks, Graig.

George, do you want to answer that question?

Yeah, sure.

How we did it and how it's going.

Yeah, Graig, 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 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 DURAVYU 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 an FDA involved early in the design and execution of that site.

And our quality team has had 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 two, 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.

I 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 premium 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 DURAVYU from this site.

Colleen Kusy, Baird.

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 ex US versus US sites.

Can you speak to whether you'd expect a meaningful difference in the type of patients you're enrolling in LUGANO and LUCIA?

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 question, Dr. Ribeiro, who, of course, was quite involved in 1 of the international GA studies.

So Ribeiro, what do you think?

Yeah.

No, good question.

And I think if we go back on the GA trial, I think there was something that could be one of the hypotheses, but I'm not sure if it was really confirmed that the geographical difference were one of the reasons for the difference in the results Regardless, wet AMD studies are much more mature than GA trials across the globe, right?

So clinical sites have been doing this working these studies for many, many years.

I think we nailed down our inclusion exclusion parity to accommodate global study.

So I don't expect to see baseline characteristics being much different between the US and ex US sites.

Great.

That's helpful.

And one quick one, if I can.

On DME, -- does the FDA have the same noninferiority margin of minus 4.5 liters on the lower bound of the confidence interval as they do in wet AMD.

Ribeiro, do you know historically how the monopolar has been calculated in DME?

Yeah.

So for DME, of course, it's going to be part of our discussion with the FDA and EMA, but I think if you look back on 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 interactions.

Debanjana Chatterjee, Jones.

Hi, thanks for taking my question.

So in terms of future market positioning, how would DURAVYU's potential every 6-month label compared to [EXPAREL] potentials every 6 months, every 12-month label that Ocular has guided to.

Thanks for the question.

I think in every 6-month label is what the physicians I think, prefer.

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 DURAVYU to consistently deliver therapeutic levels of vorolanib for 6 months in virtually everybody.

So that we like our label.

We like our study design, and we think the 6-month label will deliver that flexibility to patients and physicians to help tailor their individual treatment to maximize the vision, maximize the drawing effect while minimizing the necessary visits and injections.

I have a quick follow-up.

The way things are stacking up, DURAVYU could still be the for-to-market durable TKI.

How would you use this -- I mean, lead time over (inaudible) to capture the market?

Well, that's a really interesting question because it's quite broad.

And -- 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 to market especially driven by this great enrollment that we've talked about today.

In saying that, we've had an early program work done here for the past 2 years on exactly how we are going to position DURAVYU.

And it is a shift in the market, a true 6-month repeatable, safe, tolerable treatment for VEGF-mediated disease is you could argue with there really is nothing like that right now so that the idea of how to get physicians comfortable with it is the 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 that just like we've been on the forefront of figuring out manufacture for commercial.

We've been testing the market, interviewing KOLs talking to payers, talking to the business people at the retina groups in order to best position ourselves.

Greg Harrison, Scotiabank.

Hey, good morning, thanks for taking the question.

I wanted to ask about your cash runway guidance and whether that includes assumptions for -- or what assumptions that includes for work in DME and the earlier pipeline?

And then separately, what is the current status of the razuprotafib 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 3 data.

And so our guidance includes, obviously, everything associated with DURAVYU and wet AMD.

It includes our ongoing work in preparation internally for an eventual DME study but not the study itself.

As far as razuprotafib goes, our preclinical 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 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.

Yale Jen, Laidlaw and Co.

Great.

Thanks for taking the question.

Congrats on the progress.

Just two from us.

The first one is that 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 results in the first quarter of 26%.

Any readthrough from these two statements?

And then I have a follow-up question.

Sure.

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

Whether the first trial, which was not run concurrently reads 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 LUCIA.

Once again, as we look at the rate that we're recruiting, we remain confident that LUCIA 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 more follow-up here. which is that a few years ago, you reported the [supplement] free patients subcu 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 3 study?

Yes.

Great question.

Yes.

I'm going to let Ramiro answer that.

Yes.

No, good question.

And I think you already mentioned the limitation of the study being a small study.

So I think we've deemphasized it's a little bit hard to predict which patients are going to be supplemental 3.

Of course, once we have a larger database with the Phase 3 program, then that's something that we might be able to look at.

Yi Chen, H.C. Wainwright.

Thank you for taking my question.

Could you talk about whether you currently have a plan to initiate a Phase 3, trial in DME at this point potentially late 2025 or 2026.

If not, do you plan to find a partner potentially moving this indication forward?

And what would be the target enrollment suggested by VERONA results in a potential Phase 3 concept?

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 event, at this point.

And we would certainly welcome a potential partner, but we're not going to partner in indication individually.

A partnership that might include clinical 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.

As for the target again, I think maybe Ramiro, you might be able to answer that better about how we would approach the targets.

Yeah.

And I think we have a great benefit of having the wet AMD study in a lot of the learnings as well as the relationship we are building with the sites now.

So we know that for DME clinical sites, they would be very likely the same one as we are using for wet AMD trial.

So I think in terms of enrollment rates, we would also be optimistic for a DME trial.

Thank you.

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