EyePoint Pharmaceuticals Inc (EYPT) 2022 Q3 法說會逐字稿

EyePoint Third Quarter 2022 Financial Results conference call. (Operator Instructions) As a reminder, today's conference call is being recorded. I will now turn the call over to the host Mr. George Elston, Chief Financial Officer of EyePoint Pharmaceuticals. Please go ahead, sir.

Thank you. And thank you all for joining us on today's conference call to discuss EyePoint Pharmaceuticals Third Quarter 2022 Financial Results and recent corporate developments. With me today are Nancy Lurker, President and Chief Executive Officer; Dr. Jay Duker, Chief Operating Officer and Scott Jones, Chief Commercial Officer. Nancy will begin with a review of recent corporate updates. Dr. Duker will then discuss Phase II clinical trials for EYP-1901 and Scott will comment on our third quarter 2022 commercial performance. I will close with commentary on the third quarter of 2022 financial results, and we will then open up the call for your questions.

Earlier this morning we issued a press release detailing our financial results as well as commercial and operational developments. A copy of this release can be found in the investor relations tab on the corporate website, www dot eyepoint 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 safe harbor provisions under the Private Securities Litigation Reform Act of 1995. This includes statements about our future expectations, clinical developments, regulatory matters and timelines, the potential success of our products and product candidates, financial projections and other 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 factor section of 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. 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 Nancy Lurker, President and Chief Executive Officer of EyePoint Pharmaceuticals.

Thank you, George. Good morning, everyone. And thank you for joining us to discuss the continued progress that EyePoint made in the third quarter of 2022. Despite the challenging macro-economic conditions, we are well funded to reach our critical readouts. And we remain optimistic about the direction we're headed in as we work to bring innovative ocular therapies to patients with serious eye disorder.

Prior to turn the call over to my colleagues, I'd like to highlight a few of our achievements last quarter. We continue to consistently and successfully execute important milestones across our pipeline. With the first patient dosed in our Phase II PAVIA clinical trial, evaluating the EYP-1901 for non-proliferative diabetic retinopathy or NPDR in September. Notably, this was our second Phase II clinical trial for EYP-1901 initiated in the third quarter.

As a reminder, in July, we dosed the first patient in our Phase II DAVIO 2 clinical trial for wet age-related macular degeneration, also known as wet AMD. In the 18 months since initiating our Phase I DAVIO trial, we've completed the trial and reported positive 6- and 12-month data, held a Type C meeting with the FDA for our Phase II and III clinical trial plans and initiated our Phase II DAVIO 2 clinical trial for wet AMD and Phase II PAVIA trial for NPDR, respectively. I'm very proud of these achievements, and we'll continue to execute consistently and effectively.

EYP-1901 combines the VEGF receptor-binding tyrosine kinase inhibitor vorolanib and a bioerodible formulation of our proprietary Durasert technology. EYP-1901 has the potential to provide patients a duration between treatments of 6 months or longer, while maintaining stable visual acuity and macular anatomy. It's important to highlight that we view 1901 not as a replacement for current standard of care large molecule anti-VEGF treatments, but as a maintenance therapy with a different mechanism of action.

Under this treat to maintain strategy, patients can potentially be extended 6 months or longer with EYP-1901 after becoming stabilized with anti-VEGF standard of care treatment. We are extremely excited to have successfully dosed the first patients in both EYP-1901 Phase II clinical trials as planned and look forward to providing updates on these trials in the quarters to come.

Dr. Jay Duker, will review EYP-1901's unique value proposition for patients in more detail later on the call.

Turning to our commercial business. Data from the YUTIQ CALM registry study will be presented at a poster presentation at the Retina Society 55th Annual Scientific Meeting, which is taking place right now in Pasadena, California. The CALM study is a Phase IV multicenter registry study and a joint collaboration between EyePoint and the Cleveland Clinic that will become a valuable resource in furthering the understanding of posterior segment uveitis.

Importantly, our commercial team delivered another strong quarter for YUTIQ with $7.3 million in net product revenue, an increase of 85% from the third quarter of last year, along with continued strong customer demand for YUTIQ. Scott will provide additional detail for this topic later on.

Finally, we wanted to share an update on our DEXYCU franchise. In October, the company and ImprimisRx mutually terminated an agreement with the commercialization of DEXYCU effective December 31, 2022. This was a result of CMS' proposed hospital outpatient rule published in July, which did not contain an extension of the pass-through payment period for DEXYCU beyond December 31 of this year.

The final 2023 CMS HOPPS rule, which was published yesterday, November 1, did not modify the proposed rule. This loss of pass-through status at the end of this year will significantly reduce the amount of Medicare reimbursement provided to the company's DEXYCU customers and will result in a significant reduction in the company's DEXYCU product revenues. We are actively looking at all the strategic options for the asset, and we'll provide additional updates in subsequent quarters.

I'd like to thank the talented EyePoint team for our company's success to date. As we advance the future of sustained ocular drug delivery, we look forward to continued execution on multiple near-term clinical catalysts so that we can become the leader in sustained ocular delivery and ultimately create a better future for patients living with these serious eye disorders.

I'll now turn the call over to Dr. Jay Duker, our Chief Operating Officer, to provide an update on our lead program, EYP-1901 as well as other initiatives. Jay?

Thank you, Nancy, and good morning, everyone. Before I begin, I want to reiterate what a productive quarter this has been for the EyePoint clinical team as we executed on multiple milestones, further advancing our innovative pipeline.

Turning to our product pipeline, EYP-1901 is an investigational sustained release therapy using a bioerodible formulation of our Durasert technology with vorolanib, a tyrosine kinase inhibitor that binds the receptor, therefore, blocking all isoforms of VEGF.

Vorolinib's differentiated mechanism of action in the standard of care ligand blockers may provide additional benefits such as neuroprotection. Compared to other TKIs, vorolanib features reduced off-target binding, leading to a potentially improved safety profile with no reported ocular toxicity. Durasert has a proven and safe sustained-release delivery platform differentiates EYP-1901 from other agents targeting VEGF mediated retinal disease as this bioerodible insert allows for true sustained release of the drug with 0 order kinetics with up to 9 months' duration of activity.

In wet AMD, EYP-1901 is being studied as a maintenance therapy following induction therapy with a standard of care anti-VEGF therapeutic, a new treatment paradigm, which we call treat to maintain. Our goal is to sustain the majority of wet AMD patients' treatment interval up to 6 months or longer with a single injection of EYP-1901. By providing the sustained delivery therapy, patients and practitioners can potentially have the flexibility to safely reduce the number of visits to their retina specialists through controlled and sustained intravitreal delivery of a differentiated anti-VEGF drug.

Turning to non-proliferative diabetic retinopathy or NPDR, it is a very common disease, affecting almost 1/3 of diabetic adults over the age of 40, and it's projected to impact over 14 million Americans by 2050. In NPDR, blood vessels are weakened, and this may lead to both swelling of the macula and abnormal blood vessel growth. If left unchecked, NPDR can be the harbinger of severe visual loss as well as other ocular complications.

Because the currently approved therapies for NPDR require a significant visit and treatment burden, 97% of NPDR patients are currently observed. This provides a significant market opportunity for EYP-1901, which may be able to be effectively delivered at a 9-month interval or longer in NPDR.

Revisiting the Phase I DAVIO clinical trial for EYP-1901, we recently reported positive 12-month safety and efficacy results at the American Academy of Ophthalmology meeting in Chicago. The DAVIO trial enrolled 17 patients and each received a single intravitreal injection of EYP-1901 at 1 of 4 different dose levels. All enrolled patients were previously treated with standard of care anti-VEGF therapy. No reinjection with the study drug was performed during the trial and typical criteria for supplementation with the standard of care anti-VEGF was employed.

We were pleased that the 12-month data featured no reports of ocular SAEs or drug-related systemic SAEs, no reported events of vitreous floaters, endophthalmitis, retinal detachment, insert migration to the anterior chamber, retinal vasculitis, poster segment inflammation or retinal vascular occlusive events. Further, the 12-month follow-up confirmed stable best corrected visual acuity of minus 4.12 ETDRS letters and stable central subfield thickness on OCT of minus 2.76 microns. Interestingly, 1/3 of eyes were supplemental anti-VEGF free up to 12 months after a single injection of EYP-1901. Up to 6 months, 53% of eyes were supplement free.

Additionally, there continued to be positive treatment burden reduction of 73% at 12 months compared to 75% at the 6-month visit. On the heels of these positive data, we enrolled our first patients in 2 separate Phase II clinical trials of EYP-1901, one for the treatment of wet age-related macular degeneration called DAVIO 2 and one studying the drug in non-proliferative diabetic retinopathy called the PAVIA study.

The DAVIO-2 trial is expected to enroll approximately 150 wet AMD patients previously treated with a standard of care anti-VEGF therapy and randomly assign to 1 of 2 doses of EYP-1901, approximately 2 milligrams or approximately 3 milligrams versus an on-label aflibercept control.

EYP-1901 is delivered with a single intravitreal injection in the physician's office similar to current FDA-approved anti-VEGF treatments. The primary efficacy endpoint of the DAVIO-2 trial is non-inferiority to the aflibercept control as measured by change in best-corrected visual acuity 6 months after the 1901 injection.

Secondary efficacy endpoints include change in CST as measured by OCT, time to first supplemental anti-VEGF, reduction in treatment burden and safety. We look forward to progressing the DAVIO 2 trial and anticipate top line results in the fourth quarter of 2023.

The first patient was dosed in the Phase II PAVIA clinical trial of EYP-1901 for the treatment of NPDR in September of 2022. The trial is expected to enroll approximately 105 patients randomly assigned to 1 of 2 doses of EYP-1901, approximately 2 milligrams or approximately 3 milligrams or to the control group, which will receive a sham injection. In this trial as well, EYP-1901 is delivered with a single intravitreal injection in the physician's office. The primary efficacy endpoint of the trial was improvement of at least 2 diabetic retinopathy severity scale levels at week 36. Secondary endpoints include onset of vision-threatening complications, occurrence of diabetic macular edema and/or proliferative disease, retinal ischemia nonperfusion and safety.

In summary, we are very proud of the clinically validating results we've seen from the Phase I trial of EYP-1901, and we are excited to provide updates on the DAVIO 2 and PAVIA trial in the quarters to come.

I will now turn the call over to Scott Jones, Chief Commercial Officer, for the commercial update. Scott?

Thank you, Jay. We're excited to report a strong quarter for our commercial business with $9.7 million of net product revenue, an increase of 13% from the third quarter of last year. Our Q3 net product revenue for YUTIQ and DEXYCU was $7.3 million and $2.4 million, respectively.

Customer demand for the third quarter was approximately 890 units of YUTIQ; 14,100 units of DEXYCU. Customer demand for YUTIQ continues to grow as we see positive traction from our focus on retinal specialists for posterior segment inflammation and continued use by uveitis specialists.

We hope to see increased demand continue in the quarters to come with further support from the ongoing Phase IV studies that are currently underway. As Nancy previously discussed, in October 2022, the company mutually terminated an agreement with ImprimisRx for the commercialization of DEXYCU effective December 31, 2022, as a result of the Medicare hospital outpatient prospective payment system and the ASC payment system proposed rule, which was published in the Federal Register by the Center for Medicare and Medicaid Services on July 26, 2022.

The final rule published yesterday did not contain an extension of the pass-through payment period for DEXYCU beyond December 31, 2022. We will work with the ImprimisRx team supporting the DEXYCU franchise through Q4, while also actively looking at all strategic options available to us for the asset.

We're very pleased by the progress that we've made with our commercial businesses and remain on track for breakeven for the franchise in 2022. I'd like to thank our commercial teams for their dedication in bringing our ophthalmic therapies to physicians and patients in need.

I would now like to turn the call over to George to review the financials. George?

Thank you, Scott. As the financial results for the 3 months ended September 30, 2022, 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, 2022, total net revenue was $10 million compared to $9.1 million for the quarter ended September 30, 2021. This includes net product revenue for the third quarter of $9.7 million compared to net product revenue of $8.6 million for the prior year period, an increase of 13%.

Net revenue from royalties and collaborations for the third quarter ended September 30, 2022, totaled $0.3 million compared to $0.5 million in the corresponding period in 2021. Operating expenses for the third quarter ended September 30, 2022, totaled $28.4 million versus $24.4 million in the prior year period, primarily driven by an investment in personnel across the organization, including noncash stock compensation and ongoing clinical trial and development costs for EYP-1901.

Nonoperating expense net totaled $0.02 million and net loss was $18.4 million or $0.49 per share compared to a net loss of $16.7 million or $0.58 per share for the prior year period.

Cash and investments at September 30, 2022, totaled $157.3 million compared to $171.2 million at June 30, 2022. We expect cash, cash equivalents and investments on hand at September 30, 2022, and expected net cash inflows from our product sales will enable us to fund our current and planned operations into the second half of 2024.

In conclusion, we are pleased with EyePoint's progress in the third quarter of 2022 and are well capitalized to advance our product pipeline to key value inflection points. Thank you all very much for listening this morning. And I'll now turn the call over to the operator for questions.

(Operator Instructions) Our first question comes from Jennifer Kim of Cantor.

I see here, maybe to start off, how do you think about the positioning of sustained release therapies on the back of the detailed high-dose EYLEA data?

Yes. So first of all, I want to stress a couple of things and then I'm going to have Dr. Duker elaborate. It's very important that people realize this is meant as maintenance therapy EYP-1901. So we've never viewed ourselves as a competitor to the large molecule anti-VEGF and as we also have shown in our Phase I data, we are able to get a majority of patients out beyond 6 months.

The other thing to consider is that as we further develop the product, we're continuing to work on the mechanism of action, and it is a different mechanism of action. And generally speaking, that can be a positive when you look at approaching the disease from multiple angles. And we've got some interesting preclinical animal data that Jay can elaborate on, which we believe further highlights.

There could be some additional benefit to using a different mechanism of action, while you occasionally may need to supplement with a large molecule antibody -- excuse me anti-VEGF. Jay?

Well, thanks for the question, Jennifer, to elaborate a little bit more on what Nancy said and just to go over the data. Regeneron announced that about 77% of their wet AMD patients within the study could be dosed at an extended time frame up to 4 months. In our DAVIO trial, we had 76% of eyes go out that log. And in addition, of course, we had 53% go up to 6 months without a rescue or supplement. And we had 1/3 of eyes go 1 year. And those are findings that really the ligand blockers are unable to achieve.

So to differentiate on just the basis of longevity, I think that we have the possibility of going significantly longer with a single injection. We don't have to do that in everybody to have a very successful product. If you again look at our DAVIO data, even the patients who required a supplement before 6 months, in general, those patients received much less treatment than they had been getting prior. So that reduction in treatment burden from every month or 2 will still be a benefit to patients even if they require treatment every 3 to 4 months with EYP-1901.

And finally, the differentiated mechanism of action, I think Nancy touched on this, but we do have some preclinical data in a retinal detachment model that suggested that vorolanib, which is our tyrosine kinase inhibitor showed neuroprotection, both measuring vision in affected animals as well as looking at the OCT findings of the outer retina in this retinal detachment model. So we're certainly encouraged by that, and we're looking at other preclinical evidence of other mechanism of action that may differentiate vorolanib from the standard of care. And of course, the clinical data we hope will bear that out as well.

Okay. That's really helpful. My second question is, I know it's a little early, but any color around the rate of enrollment in DAVIO 2, and I know it's even earlier, but in PAVIA.

Yes, go ahead, Jay.

Yes. So I would say the onset, the first patient dosed in the DAVIO 2 trial was exactly where we planned. In saying that, I think the initial enrollment is a bit slower than what we hoped for. That had a lot to do with the rolling out of the sites. Now we have a lot of sites up and running and we are now enrolling at a respectable clip. And we still, at this point, believe we'll have top line data to share in approximately a year in the fourth quarter of next year.

PAVIA, again, right on target at this point. I think because of -- as Nancy used the term macroeconomic, because of macroeconomic factors at both the CROs and the sites, it's been a little slower getting the sites up and running. But once the sites are up and running, then the enrollment is going just fine.

Okay. Very helpful. And then my last question is, you mentioned actively looking for alternative paths around DEXYCU. Could you give a bit more color on that and when we might get an update?

So let me just comment on that, which is that we're going to look at potential partnerships because I just want to remind everyone, CMS has indicated they will provide reimbursement should you have a pain indication. And given that we have an FDA-approved drug, still retains significant value with a patent life out until at least 2035.

So we are going to be looking at various options to potentially complete those pain studies, but nothing definitive yet, and we'll be back as soon as we -- to the investors as soon as we nail down exactly what we're doing.

One moment, please. Our next question comes from the line of Georgi Yordanov of Cowen.

One is regarding some of the interesting data that you presented, the subset analysis from DAVIO and patients with no residual fluid. So maybe we're just wondering if you can, kind of, like, dive deeper into those results, they seem very impressive. Do they, in any way, kind of, like, inform future designs of the pivotal trials or in, kind of, like, anyway clarify the opportunity there? And then we have a couple of follow-ups.

Yes, Jay.

Yes, I'd be happy to answer that. So first of all, what Georgi is referring to is we went back in the DAVIO data the Phase I data and looked at the patients who entered the study dry with no excess fluid. Remember, we didn't have any fluid cutoffs in the DAVIO trial for enrollment. We enrolled patients who, under good control, bad control, we really took all comers. 9 of the patients of the 17 were dry going in, and those patients did exceptionally well with about 67%, I think, up to 6 months without a supplement within the first 6 months, the 3 that didn’t need supplement only needed one. The change in visual acuity in the first 6 months was about a letter minus. And the OCTs were -- looked good. And so that subset of patients did very well.

So parenthetically, I got asked the question by Jennifer earlier about high-dose EYLEA. Well, high-dose EYLEA, if you look at the data, above 50% of regular dose EYLEA patients at 16 weeks are dry, high-dose EYLEA of 60%. So if this data holds for EYP-1901, that dryer eyes do better, in some ways, high-dose EYLEA may actually be a better drug to lead into 1901 than regular EYLEA is because more eyes will be dry.

How does this inform us? Well, again, we are really trying to enroll patients who are basically doing well on anti-VEGF therapy in DAVIO 2 and we're not excluding a little bit of fluid because there's certainly evidence that a little bit of subretinal fluid is may be protective to visual acuity in the long term. But you also may recall, and I'll remind everybody on the call that every patient in DAVIO 2 is getting a loading dose of EYLEA.

And so even these are patients who are previously treated, we're loading up everybody with 3 monthly injections. And that should also increase the number of patients who, at the time they get EYP-1901 are dry. And so that should, we hope, result in more robust findings in DAVIO 2 than what we saw in DAVIO 1.

Great. It's super helpful. And then there is another follow-up. I guess, just broadly on the technology, really shown that the Durasert technology is a powerful platform. So maybe can you speak to your opportunities to bring any other molecules to Durasert? One area we've been following where Durasert could be particularly beneficial would be GA. So can you maybe just talk through the strategic considerations of potentially exploring that area?

Well, I'll comment on that, and thank you for the question. We're actively engaged in that. However, these things take time. And beyond that, we're not going to go into specifics because, obviously, we want to keep things confidential in terms of some of the specifics that we look at. But we do believe that this could be a significant opportunity.

And I'll let Jay comment on the opportunity with GA in a longer treatment duration.

Well, I think we all hope that we will have an approved drug for geographic atrophy in the near future. And if we do, it looks as if the approved drugs, the ones that are being looked at, what we hope shortly approved drugs, will have to be delivered quite frequently, probably every month to be effective. So clearly, if there is a delivery system that can deliver an anti-complement, that's safe and effective that could go out longer than that, that would be a tremendous advantage. I think that's obvious.

So in order for us to be a differentiator, we have to be able to take a molecule and put it into Durasert and be able to deliver it for that period of time. And so there's a lot that goes into the evaluation of such a molecule, size, solubility, the dose you actually need to achieve the clinical endpoint.

And so as Nancy indicated, this is an area that we are actively looking at. And when we have some positive news, we will certainly announce it.

I will add, though, neuroprotection, which I touched on briefly is another area that is a bit of a holy grail for posterior segment disease. And while neuroprotection as a mechanism of action is a little less defined, I would say, than complement inhibition and geographic atrophy.

Neuroprotection opens up a lot of other markets. And so that's another area in general, where we're looking at molecules that can provide neuroprotection to the retina or to the ganglion cells in a sustained release delivery system.

Great. Thank you for all the details, and congratulations on the progress.

Thank you.

One moment, please. Our next question comes from the line of Yi Chen of H.C. Wainwright.

So for the patients enrolled into the Phase II PAVIA trial for NPDR, are these newly diagnosed patients or existing patients who are receiving active treatment or existing patients who are not receiving active treatment?

Jay, go ahead.

Well, so active treatment would be an exclusion. So NPDR patients, in general, see well and have minimal symptoms. NPDR is diagnosed in the doctor's office based on examination of the fundus. We do know that NPDR is a progressive disease and left unchecked, it will eventually progress and in many cases, go on to diabetic macular edema or proliferative diabetic retinopathy.

So these patients could be newly diagnosed. If they're newly diagnosed, it doesn't mean they just had diabetes for a short period of time in order to get moderate to severe NPDR, you really have to have diabetes for a while, but they may have just come in to a doctor's office for the first time. So in a sense, they could be newly diagnosed. But if they're being actively treated for the complications of DME or PDR, then they won't be eligible for the study.

Okay. So these are moderately severe to severe NPDR patients. And they usually reject treatment even after diagnosis by the ophthalmologist, correct?

Yes. I think the -- to say -- I'm not sure they reject it more than most retina specialists still are reluctant to offer it. And so there are 2 approved drugs for the treatment of non-proliferative diabetic retinopathy and our research to the market suggests that no more than 2% to 3% of patients are actually getting the drugs because they require at the beginning monthly treatment. And after a while, you can cut back a little. But if you go too far the cutback of treatment, then you're going to lose the effect. So it really has to be something like a sustained release that would enable these patients to go on with their lives normally and not be tied into the doctor's office.

Because remember, these NPDR patients are not patients who are typically visiting the doctor every month or 2. They may be on a 6-month to 1-year schedule. So if they're asymptomatic with good vision, asking them to undergo an injection monthly for an asymptomatic condition is a big lift. So I don't think it's just patient reluctance. I think there's some physician reluctance there too.

Got it. Got it. And I don't know if you can provide any color on the potential growth trajectory of YUTIQ in 2023 at this point?

Yes. Sorry about that, I was on mute. So I'll let Scott comment on it, but we don't give forward guidance. However, we continue to have some very good quarters. And Scott, do you want to just comment a little bit on our approach with YUTIQ.

Sure. Thank you, Nancy. Yes, as Nancy mentioned, we will not provide guidance for the fourth quarter or for future quarters. However, I would say that a month into the fourth quarter, we're very pleased with the performance of the product. And we -- what we have seen coming out of the third quarter is that physicians, kind of, fully back in the office, and we're starting to see a lot more patients flowing through. And as you can imagine, that provides a lot of more opportunities for treatment.

I would say that, as I mentioned previously in the discussion, we have been really pleased with the uptake of YUTIQ overall in the marketplace, especially within the retinal segment as we're seeing a lot of retina physicians, a lot of new retina physicians come on board in terms of utilizing YUTIQ. And so we see that as a nice harbinger for the future.

One moment please. Our next question comes from the line of I-Eh Jen of Laidlaw & Company.

My first question is that for the DAVIO 2 study, how many sites currently being enrolled and what will be the target number of sites for the -- to be eroded in the study?

Yes, we're not going to disclose that. But suffice it to say it's typical. So we don't go into that level of detail on our clinical studies.

Okay. No problem. Just 2 more quick ones. The first one for the PAVIA study and the readout is the 2 (inaudible) level changes. Does this implant also could be used for the future pivotal study or you're thinking about something else?

Jay, go ahead.

No, that would be, as of now, the endpoint for the future pivotal studies. That is an approvable endpoint. Both LUCENTIS and EYLEA were approved for NPDR based on that endpoint. And so that the plan right now would be to use that as the endpoint in the pivotals.

Okay. Great. And maybe the last question here is that the assumption for the runway, would that include a very minimum DEXYCU revenue as the base case?

George.

I can answer that. Thank you for that. Yes. We guided about DEXYCU in Q2. We kind of knew that the pass-through extension was unlikely. And so that's always been -- the reduction in DEXYCU revenues has always been part of our cash projection.

Recall that we brought in ImprimisRx as a commercial alliance partner back in 2020. So it's been a noncore program for us. And while yes, it's been breakeven, it wasn't a significant component of our cash generation.

Okay. Great. And I look forward to see the progress.

Thank you.

Our next question comes from the line of Daniil Gataulin of Chardan.

Just a quick one on, I guess, on a bigger big trend long term. Can you comment on the plans with regard to other anti-VEGF indications such as plans for RVO?

Yes, go ahead, Jay.

Yes. So the next indication, which we plan on pursuing, is diabetic macular edema and the current plans we expect to initiate that study in the second half of next year. We will probably do RVO at some point. We don't have it built into our models yet.

Again, RVO is a much smaller market than the others. And while we think there probably will be benefit, that's not in our current plan, but we expect as we unfold with the pivotal trials for wet AMD and NPDR that will come more into focus.

I'll also add there's other smaller indications, which we will probably layer on eventually as well like myopic corneal neovascularization. We expect that 1901 would do very well in that indication. And we're also looking at the possibility of using EYP-1901 in a high-risk eye -- in other words, an eye that has dry macular degeneration, but has not yet converted to wet macular degeneration. Using EYP-1901 as a preventative, kind of, maintenance therapy to prevent the conversion to wet.

There's considerable evidence from the oral studies of vorolanib in wet AMD that there was a protective effect with this LOI. So that's another potential indication that we will be modeling and looking out in the future.

Got it. That was very helpful.

Our next question comes from the line of Yuan Zhi of B. Riley.

Can you remind us the market opportunity of NPDR patients? And when you look at the treatment landscape, what do you think could be the standard of care 2 years later when you are planning or initiating your potential Phase III trials in NPDR?

Yes. Scott, you can answer the market opportunity. And then, Jay, on the clinical side.

Thank you for the question. Yes. As you're certainly well aware of the diabetes. Our population with diabetes is continuing to grow and is a substantial number of patients at this point. It could be numbering as many as 15 million patients who are flowing through some form of ophthalmology practice or ophthalmologist practice.

We believe that certainly, the opportunity, as we said, is extremely large. Jay, I think, did a really good job of laying out, kind of, the current conundrum as it relates to the treatment paradigm, which we believe we certainly offer a really unique opportunity moving forward.

Jay.

Yes. So it's hard to project anything in this data age. But looking realistically at the 2 FDA-approved drugs for NPDR, it's hard to believe that the market is going to open up substantially in the next 2 years. I think inroads will be made. I think more of the young doctors might be more interested in pursuing an aggressive treatment of NPDR by aggressive, I mean frequent injections.

But again, in this patient population who are generally younger and working, it's hard to think in an asymptomatic disease, they're going to want to come in that frequently and subject themselves to the small but finite risk of multiple injections.

Other sustained release products are going to, I'm sure, look at the NPDR market. But this, again, is a risk-benefit kind of thing. The refillable port technology, I would expect if Lucentis is effective, it would be as well, but that may not meet the standard of risk versus benefits.

And again, I think some of the other products out there, gene therapy is potentially a pathway to have sustained release of any drug, too, but that remains to be tested. So we think that there's still going to be in 2 years, substantial opportunity for in every 9-month or perhaps even once a year, intravitreal in-office bioerodible injection that could substantially alter the course for the positive in many patients with NPDR.

I'm showing no further questions at this time. Ladies and gentlemen, this does conclude today's conference. Thank you all for participating. You may now disconnect. Have a great day. Thank you.