EyePoint Pharmaceuticals Q3 2023 Earnings Call Transcript

Quartr
Provided by Quartr
November 1, 2023

There are 9 speakers on the call.

Operator

Good morning. My name is Leeray, and I will be your conference operator today. At this time, I would like to welcome everyone to the EyePoint Pharmaceuticals Third Quarter 2023 Financial Stores and Recent Corporate Development Conference Call. There will be a question and answer session to follow at the completion of the prepared remarks. Please be advised that this call is being recorded at the company's request.

Operator

I would now like to turn the call over to George Elton, Executive Vice President and Chief Financial Officer of the EyePoint Pharmaceuticals. Please go ahead.

Speaker 1

Thank you, and thank you all for joining us on today's conference call to EyePoint Pharmaceuticals' Q3 2023 financial results and recent corporate developments. With me today is Doctor. Jay Duker, President and Chief Executive Sure. Jay will begin with a review of recent corporate updates and discuss the ongoing Phase 2 clinical trials for EYP-nineteen oh one. I will close with commentary on the Q3 2023 financial results and we will then open the call for your questions.

Speaker 1

Earlier this morning, we issued a press release detailing our financial results and recent operational developments. A copy of the release can be found in the Investors tab on the corporate website, www.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 timelines the potential success of our products and product candidates financial projections and our plans and prospects. Actual results may differ materially from those indicated by these forward looking statements as a result of various important factors, including those discussed in the Risk Factors section on our most recent Annual Report on Form 10 ks, which is on file with the SEC and in other filings that we may make with the SEC in the future.

Speaker 1

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 Pharmaceuticals.

Speaker 2

Thank you, George. Good morning, everyone, and thank you for joining us to discuss EyePoint's continued execution toward our milestones as we work to bring 1st in class therapeutics and delivery technologies to patients suffering from serious retinal diseases. In the Q3, we both advanced and expanded our product pipeline with the announcement of positive masked safety data in our ongoing Dovio-two and PAVEA Phase 2 clinical trials for our lead product candidate EYP1901, which is the small molecule virolinib and our proprietary bioerodible Durasert E technology, as well as the unveiling of a new preclinical program EYP-two thousand three hundred and one. EYP-two thousand three hundred and one delivers a promising Tie2 activator, rasuprotofib, formerly known as AKB-nine thousand seven hundred and seventy eight, formulated in Durasert E to potentially improve outcomes in wet age related macular degeneration or wet AMD and diabetic eye disease. It's an exciting time at EyePoint as our EYP-nineteen oh one clinical trials approach key data events with top line Phase 2 DAVIO-two trial results anticipated in early December and PEVEA results in Q2 of next year.

Speaker 2

And as we plan to initiate a 3rd Phase trial in diabetic macular edema or DME in Q1 of 2024. I'll now review our recent program and corporate updates and give an overview of upcoming catalysts. Turning to our lead program, EYP-nineteen oh one is being advanced as a potentially paradigm shifting treatment for patients suffering from VEGF mediated retinal diseases. EYP-nineteen oh one is delivered with a single intravitreal injection in the physician's office similar to the current FDA approved anti VEGF biologic treatments. EYP-nine thousand two hundred and one is immediately bioavailable featuring an initial burst of drug followed by near constant 0 order kinetic release for approximately 9 months.

Speaker 2

EYP-nineteen oh one delivers virolinib, a selective and patent protected tyrosine kinase inhibitor Formulated in a solid insert using our proprietary sustained release bioerodible Durasert E technology. For Roland, it brings a new mechanistic approach to the treatment of VEGF mediated retinal diseases by acting as a pan VEGF receptor blocker, blocking all VEGF isoforms. We expect EYP-nineteen oh one with its new MOA and sustained drug delivery for up to 9 months to meaningfully reduce treatment burden in the majority of wet AMD patients, while keeping vision and retinal anatomy stable. Verolanab features reduced off target binding and at clinically relevant doses does not inhibit Type 2, a critical pathway associated with vascular stability, which may result in an improved efficacy. In a rodent model of retinal detachment, Veroenib demonstrated neuroprotection and because it blocks PDGF may also have anti fibrotic benefits.

Speaker 2

We were pleased to present preclinical and clinical data at multiple medical meetings that underscore the promising profile of EYP-nineteen oh one. One highlight was at last month's Retina Society meeting where a comparison of the anti androgenic profile of 3 TKIs virolinib, axitinib and sutinib validated virolinib as a pan VEGF receptor inhibitor that effectively blocks the critical pathways of pathologic angiogenesis. Importantly, the data showed that voronib is differentiated from the other GKIs tested at retinal disease. Unlike sunitinib, virolinib does not bind to melaninib. And unlike axitinib, vironolinib is not expected to have a physiologic impact on normal type 2 function.

Speaker 2

As a reminder, the fully enrolled Dovio-two trial is evaluating EYP-nineteen oh one in 160 subjects with previously treated wet AMD as a maintenance therapy with a goal to maintain stable vision and retinal anatomy for the majority of wet AMD patients for 6 months or longer following a single injection of EYP-nineteen oh one. This could represent a significant improvement compared to the current anti VEGF treatments that are dosed on average every 2 months in the United States under a treatment extend protocol. This lifetime of frequent treatment represents a tremendous burden for patients, physicians and the healthcare system in general. EYP-nineteen oh one has the potential to change this treatment paradigm into a treat to maintain model by providing sustained delivery of erolimus for approximately 9 months following induction treatment with a large molecule anti VEGF Ligand walker. This may allow patients and practitioners the flexibility to reduce the number of visits without sacrificing visual outcomes.

Speaker 2

The subjects in the DAVIO-two trial were randomized to 2 treatment arms, approximately 2 milligrams or approximately 3 milligrams of EYP-nineteen oh one or on label aflibercept as a control. All subjects to the trial received 3 loading doses of aflibercept on day 1, month 1 month 2 followed by dosing of BYP-nineteen oh one or a sham injection 30 minutes after the last loading dose. The FDA approval pathway for this program And the primary endpoint for WAVE-two is non inferiority in the change of best corrected visual acuity or BCVA for each of the 1901 arms versus the eflibercept control arm. The lower limit of non inferiority margin is defined as minus 4 point Five letter loss by the FDA. For perspective, patients do not generally notice a change in vision until they lose 5 or more letters, which is the equivalent of one line on an eye chart.

Speaker 2

I'd like to share our perspective in terms of targeted outcomes for the non inferiority BCVA as there are both numerical and statistical considerations for this outcome. First, a very successful outcome in Dovio-two would be to mirror the Phase 1 Dovio BCVA results that showed an average of 2.5 letter loss 6 months after EYP-nineteen oh one was injected. Recall that Dovio was an all comers, open label, non randomized Phase 1 trial. Based on learnings from that Phase 1 trial, we modified inclusion and exclusion criteria for the DAVIO-two trial in an effort to exclude eyes that were not responding to standard of care therapy. We presented mass patient demographic data last quarter that reflects the fact that we enrolled a more controlled patient population in DOPIO-two than in the Phase 1 trial.

Speaker 2

Generally, an outcome of minus 3 letters or better would be a very strong numerical outcome and possibly statistically non inferior, even in this relatively small trial. If the EYP-nineteen oh one arms match or better the -1.4 letters difference versus the 2 milligram of flibrocept control, which was what was seen in the 16 week 8 milligram EYLEA arm in the PULSAR trial, this would represent an outstanding outcome from a single injection of EYP-nineteen oh one. In addition to stable BCVA, it is Critical that the EYP-nineteen oh one continues to show a favorable safety profile consistent with the interim mass safety update through October 1, 2023 across all of the EYP-nineteen oh one clinical trials. As of October 1, approximately 170 patients have received BYP-nineteen oh one with a minimum of 4 months follow-up post injection from the ongoing Phase II PIVEA and DABIO-two clinical trials and the completed DABIO Phase 1 trial with no reported drug related ocular SAEs and no reported drug related systemic SAEs. This continues to give us confidence in the results of this crucial endpoint.

Speaker 2

Although change in best corrected visual acuity is the primary endpoint, Reduction in treatment burden will also be a critical secondary outcome to consider, given the unmet need in this patient population for more durable therapies. For a clinically meaningful outcome, we believe that 1 or both EYP-nineteen oh one arms need to result in a reduction in treatment burden of a minimum 50% or better for the 6 months following EYP-nineteen oh one injection at week 8. In addition, we also believe that 50% or greater of the EYP-nineteen oh one treated eyes should be supplement free up to the week 32 visit, along with a relatively stable anatomy as measured by OCT. Based on our market research and KOL interactions, these endpoints will be meaningful to retina specialists who treat wet AMD patients. We plan to host a virtual call with renowned retinal specialists, Doctor.

Speaker 2

David Boyer and Doctor. David Lally on November 9 at 8 am Eastern Time to discuss their perspectives on the current treatment landscape and the Dovio-two outcome considerations that I just reviewed. We hope that you will all join us for this informative presentation and Q and A, and you can find the link to that call in the Investor tab of our website. Looking ahead to the potential Phase Three pivotal trials for EYP-nineteen oh one as maintenance therapy in wet AMD. Our current plan is to initiate the first trial by the Q4 of 2024.

Speaker 2

This initial trial will be largely in the U. S. And Canada. We hope to initiate a second pivotal trial several months later. The second Phase 3 trial will be largely outside of the U.

Speaker 2

S. The Phase 2 DAVIO-two trial of BYP-nineteen oh one was designed to mirror the anticipated design of Phase 3 trials based on our Type C meeting with the FDA and other interactions with the agency. The key differences are that the Phase 3 trials will feature re dosing of EYP-nineteen oh one every 6 months and the primary efficacy endpoint will The non inferior change in visual acuity at approximately 1 year instead of 8 months as

Speaker 3

it is in

Speaker 2

WAVE-two. We expect to share more details about this trial in the coming months. Now let me turn to our second indication NPDR. In June, we reported that enrollment of the Phase 2 PAVIA clinical trial was complete. PAVIA is a randomized controlled Phase 2 trial evaluating EYP-nineteen oh one as a potential 9 month treatment for moderate to severe NPDR.

Speaker 2

Similar to the DAVIO-two trial, our PAVIA trial saw significant investigator and patient interest during enrollment. The trial enrolled 77 patients exceeding the 60 patient target. Patients were randomly assigned to 1 of 2 doses of EYP-nineteen oh one, approximately 2 milligrams or approximately 3 milligrams or to the control group that received a sham injection. As in the wet AMD trials, CYP-nineteen oh one is delivered with a single intravitreal injection in the physician's office. As a reminder, NPDR is a very common retinal disease that affects almost 1 third of diabetic adults over the age of 40, and it's projected to impact over 14,000,000 Americans by 2,050.

Speaker 2

In NPDR, blood vessels are By 2,050. In NPDR, blood vessels are weakened, potentially leading to swelling of the macula, which is called diabetic macular edema or DME, and may eventually result in abnormal blood vessel growth, which is called proliferative diabetic retinopathy or PDR. Both DME and PDR could ultimately result in severe visual loss. It's important to note that there remains a great unmet need for safe, efficacious and convenient treatment for NPDR that proactively reduces the risk of progressing to a site threatening complication over the long term. Approximately 90% of patients with NPDR currently receive no course of therapy apart from observation by their eye doctor until their disease progresses to DME and or PDR.

Speaker 2

EYP-nineteen oh one in our Phase 2 PAVEA trial could potentially reduce the risk progressing to these complications with a less intrusive treatment protocol. Recently, we reported an interim analysis of mass safety data from the Phase 2 PAVEA clinical trial in NPDR, which showed that as of October 1, 2023, EYP-nineteen oh one was well tolerated with no reported drug related ocular or drug related systemic SAEs, demonstrating EYP-nineteen oh one's excellent safety profile in NPDR for the first time. Top line data from the PAVEA trial remains on track for the Q2 of 2024. As mentioned earlier, we plan to initiate a Phase 2 trial evaluating EYP-nineteen oh one in DME in the Q1 of 2024, which we are calling the VIRONA trial. We will share details of that trial at a future date.

Speaker 2

The goal of the VIRONA trial is to gain experience with EYP-nineteen oh one in this potentially large indication. In September, we disclosed a new preclinical program called EYP-two thousand three hundred and one. EYP-two thousand three hundred and one is tied to agonist rasoprotafim formerly known as AKB-nine thousand seven hundred and seventy eight, which we have formulated to work in Durasert E. This has the potential to provide intravitreal sustained delivery over 6 months or longer to improve the treatment of wet AMD in diabetic eye disease. Previous preclinical and clinical studies show that rasaprotofib delivered subcutaneously demonstrated proof of concept in diabetic eye disease and we believe that delivering EYP-two thousand three hundred and one intravitrally has the potential to offer new site saving treatment for patients with severe retinal disease either alone or in combination with anti VEGFs.

Speaker 2

Finally, we were delighted to announce that EyePoint expanded its Board of Directors with the appointment of Stuart Dutti, a seasoned biopharmaceutical financial executive who brings more than 25 years of experience to the role. We also strengthened our executive leadership team with the promotion of our CFO, George Elston to the additional role of Executive Vice President. George's wealth of experience, financial acumen and strategic guidance has been a tremendous asset to our EyePoint team. On behalf of the entire leadership team, we welcome Stuart and congratulate George and we are grateful for their valuable leadership at EyePoint as we continue to build value for our shareholders during this active time in the company's growth. I'd like to thank the entire EyePoint team for an incredibly productive quarter.

Speaker 2

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

Speaker 1

Thank you, Jay. As the financial results for the 3 months ended September 30, 2023 were included in the press release issued this morning, my comments today will be focused on a high level review for the quarter. For the Q3 ended September 30, 2023, total net revenue was $15,200,000 compared to $10,000,000 for the quarter ended September 30, 2022. Net product revenue for the Q3 was $800,000 compared to net product revenues for the Q3 ended September 30, 2022 of $9,700,000 Consistent with the exit from the commercial business, The decline in revenue resulted from the sale of the YUTIQ franchise in May 2023, along with the discontinuation of marketing activity for the DEXYCU franchise this year due to the loss of pass through reimbursement by CMS effective 1onetwenty 3. Net revenue from royalties and collaborations for the Q3 ended September 30, 2023 totaled $14,400,000 compared to $300,000 in the corresponding period in 2022.

Speaker 1

The increase was primarily due to a recognition of deferred revenue from the sale of YUTIQ, which will be recognized over a 2 year period, which began in Q2 of this year. Operating expenses for the 3rd quarter ended September 30, 2023 totaled $29,600,000 versus $28,400,000 in the prior year period. This increase was primarily driven by higher R and D spending on EYP-nineteen oh one clinical trials, partially offset by lower sales and marketing expense. Non operating expense net totaled $1,800,000 and net loss was $12,600,000 or $0.33 per share, compared to a net loss of $18,400,000 or $0.49 per share in the prior year period. Cash and investments at September 30, 2023 totaled $136,000,000 compared to $144,600,000 at December 31, 2022.

Speaker 1

We expect the cash, cash equivalents and investments on September 30, 2023 will enable us to fund our current and planned operations into 2025. In conclusion, we are pleased with EyePoint's progress in the Q3 year to date and are well capitalized to advance our product pipeline to key value inflection points. I will now turn the call back over to Jay for closing remarks.

Speaker 2

Thank you, George. We believe EYP-nineteen oh one is a potentially paradigm shifting treatment for patients suffering from serious retinal diseases, providing unique benefits that may include delivery of virolinib consistently over approximately 9 months, A new mechanism of action to treat retinal disease beyond anti VEGF ligand blockade, the potential for neuroprotection in anti fibrosis and a proven delivery technology with a positive safety profile. I will close by recapping key upcoming catalysts including The top line data from our Phase 2 DAVIO-two clinical trial anticipated in early December, the dosing of the first Patient in the Phase 2 Verona clinical trial of EYP-nineteen oh one in DME in the Q1 of next year and top line data released from our Phase 2 PAVEA clinical trial in the Q2 of 2024. This remains an incredibly exciting time for EyePoint as we are well positioned to execute on our upcoming milestones and continue to transform the treatment landscape with innovative long term solutions to improve both the vision and the lives of patients with serious retinal diseases. Thank you all very much for listening this morning.

Speaker 2

I will now turn it over to the operator for questions.

Operator

Thank you so much presenters. Our first question comes from the line of Tyler Van Buren of TD

Speaker 4

Good morning. Congrats on the progress. Thanks very much for the call. I have a couple of questions for you. First one is, I appreciate how transparent you guys have been with respect to your BCVA outcome scenario ranges for the DAVIO-two trial ahead of the data.

Speaker 4

But Were these constructed in accordance with KOLs? And can you elaborate on what the KOL feedback has been regarding what they need to see from the trial, Perhaps a preview of sorts of the upcoming KOL event? And then the second question is upon Positive data, can you talk about how quickly you would be able to start the Phase 3 program? And is it possible to get to top line data in accelerated Fashion or should we think of it being a more traditional wet AMD Phase 3 program timeline?

Speaker 2

Thanks, Tyler. I appreciate The question is in your interest. First of all, with respect to the BCVA ranges, So there's really kind of 3 ways to look at this. And the first way is what does the FDA want? And that's pretty clear.

Speaker 2

The non inferiority margin has got to be minus 4.5 letters. You can't cross it with your confidence intervals. And depending on your end of your study and your standard deviation, you could come pretty close to 4.5 and get a result. But the second part of what you asked is what does the KOLs want? And interestingly, when you ask them and I'm sure you have, They're generally fine with a good efficacy profile, good safety profile as long as The numerical change is in the range of 3 to 4 letters.

Speaker 2

It's interesting that I think that they Believe in general that that type of change in vision is not noticeable to the patient. On the other hand, We as a company look at it as a combination of both of those. And so that kind of minus 3 range or better, I think based on what we anticipate the standard deviation of the trial might be in a pivotal trial would likely be non inferior and meet the KOL's expectations. Of course, we don't know what the results are yet. We'll know in approximately a month.

Speaker 2

But there's reasons to believe that we could do considerably better than that. Second question was on the start of the Phase 3. With good to great data, We believe we can start the 1st Phase 3 trial in the second half of next year. It may be closer To the Q4, we haven't really zeroed in on that. Suffice it to say, the company has been really focused on Phase 3 prep for basically the last 9 months.

Speaker 2

And there's a lot to do to get ready, and we continue to be on track for our goal to start it in the second half of next year. From an accelerated perspective, I think the trouble with unmasking early is you penalize yourself with a higher end. And cost and speed is critical here. And if our statistics suggest we can do the Phase 3s with relatively low ends. I think it's best to get them done right and get them done fast as opposed to be penalized for an early look.

Speaker 2

I hope that was sufficient. Anything else?

Speaker 4

No, that's clear. Thank you very much.

Operator

Thank you so much. Your next question comes from the line of Yatin Smeh of Guggenheim. Your line is now open.

Speaker 3

Thank you for taking my question. So Jay, you just mentioned that you're focused on obviously delivering these data, but also on the Phase 3. So my question to you is and it also has to do with the competitor is, how does the Eylea induction relate to the mechanism of TKI in wet AMD? And then can you maybe just talk about why you think it is necessary for patient to do that induction when your competitors are doing a superiority study with just a single dose efiliparcept as a comparison. So I'd love to get your thoughts there.

Speaker 2

Thanks, Yatin. Those are two great questions. Let me start with the induction. First of all, from a scientific perspective, It's unclear if the induction offers anything to the patients treated with EIP-nineteen oh one. We have pretty good preclinical data that shows that our drug is bioavailable in the cohort of animals within minutes of injection and reaches therapeutic levels in hours.

Speaker 2

On the other hand, we've set out from the beginning to use UYP-nineteen oh one as a maintenance therapy for previously treated wet AMD patients. The decision to do the re induction is something that came up with our discussions with the FDA around the structure of the Phase 3 pivotal trials. When we had our Type C meeting, the FDA was certainly agreeable to us using EYLEA as our control in the Phase 3. And when we discussed on label EYLEA, the FDA's response was, yes, After you re induce the patients, you can go to every other month on label EYLEA. And the rationale was the patients you enroll in that trial may be undertreated.

Speaker 2

And therefore, before you allow them to go to every other month, you've got to re induce them. Makes sense. And then we had to reengage the FDA and said, well, if we're going to make an assumption that some of these eyes are undertreated in the real world, which we think is Probably true. We'd like to re induce all the patients in the study and they were agreeable to that. What that did, however, as you may be aware, You can have a 9 month efficacy endpoint in the wet AMD study, but our 9 months doesn't start ticking until after the reload of EYLEA.

Speaker 2

So what it was, the trade off here was we needed to do in our pivotal trial, the efficacy endpoint out approximately 1 year. We thought that was a fair trade off to be able to level the playing field and make sure that we weren't Allowing relatively undertreated patients to flood the EYPN8-two zero one arms. So it really isn't a scientific reason. I'd say it's a regulatory reason and a derisking reason that we're re inducing. So that I think gets into the second question, why induction?

Speaker 2

Again, I think I've covered that. Our decision to do this, I think more typical non inferiority Phase 3 is again It comes out of our discussions with the FDA and a derisking. We think that this is the fastest And least risky pathway to FDA approval.

Speaker 1

Yes. I'll remind you that remember we had a Type C meeting With FDA laying out the Phase II plans, which would inform Phase III. And so that's also a big driver of Focus going into the Phase 3s next year.

Speaker 3

Got it. Very helpful. Just one more question, if I may. Could you talk about the dose response? There are 2 doses in this study.

Speaker 3

So just curious what would you expect? Should we expect any dose response? Yes. And then if let's say if there is no dose response, just curious like how you will decide on the dose to take forward? Thank you.

Speaker 2

Yes. That's another great question, Jatin. And we really don't know if there will be a dose Because it's certainly possible that our 2 milligram dose will work efficiently to shut down the receptor for up to 9 months. And therefore, any additional drug may not give you additional benefit. So I would say we're, as a company, A little bit agnostic to that.

Speaker 2

I mean, it's nice to show a dose response. And there's some validation to that, Understandably. On the other hand, if both our 2 milligram dose and our 3 milligram dose work great and they're essentially the same, we would opt to go with the 2 milligram dose approximately in our pivotal trial against a lower dose most likely around 1 milligrams. What that would do of course is enable us if successful to have fewer inserts in the eye and lower the COGS.

Speaker 3

Thank you so much.

Operator

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

Speaker 5

Thanks for taking my questions. I have 2. The first is Just touching on the BCVA question. Jay, I think in your prepared remarks, you said a BCVA letter change difference of Three letters are better would be good. And I think investors are generally aligned with that.

Speaker 5

The most pushback I've gotten is on the minus 3 to minus 4 letter scenario. So I was curious to see if you have any thoughts on that scenario. Is the base Case or the hope that it will be better than that. And similar to that, in this scenario where you get a minus 3 letter difference, would STAT SIG have to assume a standard deviation better than what we've seen with, say, PDF? Thanks.

Speaker 2

Sure. Great questions, Jennifer. Thanks. So the best corrected visual acuity of 3 or less Difference. Really would be I think kind of a clear pathway in everybody's mind if we can replicate that in the pivotal trials.

Speaker 2

Minus 3 to minus 4 is a kind of a theoretical range where One could argue that with a minus, let's say, 3.5 letter difference And a large enough and in a small enough standard deviation that that could be statistically non inferior. But then you're getting into a point here where would it be commercially successful. So while it would meet that first bar of FDA approval, it may not meet the second bar of what the KOLs want and perhaps as you say what the investment community might want to see as a result. So I would say, again, centering on the three letters are better, I think that beats everybody's test for success here. I'd remind everyone that we were minus 2.5 letters in the Phase I at 6 months after the 1901 was injected.

Speaker 2

And one would expect and of course we don't know this yet, but one would expect the EYLEA control arm to be relatively stable after the load between weeks 8 week 32. And if it is And we can replicate minus 2.5 again. I think that would be really an outstanding result. So the words again, base case and it's again, I think a lot of this depends on what the view of What we need to do to advance the drug into pivotal trials. And one could See with a very tight standard deviation that even minus three letters would be statistically significant.

Speaker 2

So you mentioned the PDF standard deviations. And again, if you go back and look at the pivotal trials and wet AMD, I think basically everyone since EYLEA was approved was done on a non inferiority basis in treatment I. E. Patients and generally had standard deviations to the change in visual acuity of around 12 letters. That's because they're treatment I.

Speaker 2

E. Some eyes respond, some eyes don't. The PDS Phase 3 enrolled previously treated patients like we did, but they limited the length of time to diagnosis to 9 months prior. So some of those eyes were still relatively early in their treatment and still perhaps being treatment extended. They weren't at a stable Kind of pace of their disease yet.

Speaker 2

They had 7.1 letter standard deviation. So we have reasons to believe That because of our enrollment of eyes that had the disease longer than 9 months, Suggesting they'd be more stable, but our standard deviation could be lower than that. That answer the questions?

Speaker 5

Yes, it does. If I could One more. Your competitor received or announced that they received an agreement under their superiority trial design this morning. Net net, this Seems like good news for the overall space given the post draft guidance world we're in, but I'm wondering if you have any takes on that?

Speaker 2

Well, yes. And again, that was just announced this morning with no details. But at a high level, this is great news. It's great news for all of the TKI companies because it shows that the FDA is willing to work with us to advance this new paradigm into the clinic. And as we know, It's great for the space.

Speaker 2

When investors see that there is a clear pathway to approval, then things are derisked. From our perspective, we are very comfortable with our Phase 2 design. And if we get good to great results, At this point, I think our Phase 3 design, which the FDA has already seen and commented on and through our Type C meeting. I think that still would represent the fastest least risky way to get approval for our drug. Again, last comment about this though is once we are able to see the details of the SPA that Ochulis received, we will like any company should do is Take a look at our program and see if there's any learnings from what they're doing.

Speaker 2

But I have to again state, we're very comfortable with our approach to the pivotal trials and pathway to approval.

Speaker 5

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

Speaker 2

Thank you.

Operator

Thank you so much. Your next question comes from the line of Pauline Kuzi of Baird. Your line is now open. Celine, your line is now open. You may ask your question.

Speaker 2

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

Speaker 5

All right.

Operator

Your next question comes from the line of Daniel Gadolin of Chardan. Please go ahead.

Speaker 6

I couldn't hear that. That was my name that was called. Yes, thank you for taking the question. I have a coupon on 2,301. Wanted to ask for the Question now for this product and specifically how does it fit with 19 oh one strategy given that there could be some overlap in indications?

Speaker 6

Thank you.

Speaker 2

Thanks, Daniel. That's a great question. 2,301 is based around a molecule that's been studied into Phase 2 By a company called AirPO, we acquired their assets and their lead product AKB-nine thousand seven hundred and seventy eight was delivered subcutaneously for diabetic macular edema and for diabetic retinopathy. And it showed really promising anatomic results, although the visual results did not enable the company to really go forward into pivotal trials. This drug activates Tie 2 and by activating Tie 2 you stabilize blood vessels And you down regulate angiopoietin-two or ANG2.

Speaker 2

Now you may be aware that VAVISMO is a bispecific that blocks VEGF and blocks ANG2. So that pathway of ANG2 blockage is validated. And we believe that AKB-nine thousand seven hundred and seventy eight now EYP-two thousand three hundred and one may be a better way to block that pathway by activating Type 2. Secondly, we can now deliberate sustained release. So these bispecific molecules still require relatively frequent injections.

Speaker 2

And we believe we can deliver at therapeutic levels for over 6 months with a single injection of 2,301. So how does it fit in? Well, that remains to be seen. I think that we could develop it and test it in a non inferiority fashion to get a label against the standard of care for either wet AMD or DME or both or we could choose to go for a superiority trial using it in conjunction with an anti VEGF. That of course would be perhaps riskier because the anti vet just are so effective, it sets a really high ceiling.

Speaker 2

On the other hand, if one is successful with that approach, You would likely have a multi $1,000,000,000 product because doctors would relish the opportunity to do even better than Anti VEGF alone. How would it fit into EYP1901? You can highly speculative Because we've got a long pathway to go with 2,301, shorter pathway with 1901, but you could envision a day when both have approval as standalone in this combo and one could do it 1 of each in a single injection. Obviously, there's a long pathway to that and a lot of permutations that we're going to look at. But in a nutshell, What we believe we can do with 2,301 is activate the tie 2 pathway, secondarily inactivate ANG2 to do it in a sustained release fashion with a derisked molecule.

Speaker 6

All right. Got it. Thank you. Thank

Operator

you so much. Your next question comes from the line of Sean Kim of Jones Trading. Please go ahead.

Speaker 7

Thank you for taking my questions. I just had a couple of quick ones. So I guess for the wet AMD program following the dialy to readout, would you be requesting an end of Phase 2 trial with FDA to further guide the Phase 3

Speaker 2

That's our plan. In fact, we would plan currently on having Both the clinical end of Phase 2 and a CMC end of Phase 2 to gain alignment in both those areas.

Speaker 7

Okay, got you. And the potential timing of that meeting?

Speaker 2

I would say Late in the Q1 of next year may bleed into early Q2 of next year depending again how soon we can get All the clinical tables from W2 in a format that we can submit.

Speaker 7

Okay, Great. Thank you.

Speaker 1

That's the really

Speaker 2

limiting step here.

Speaker 7

Okay. Got you. And about To Ralli Bio complement inhibitor collaboration, what updates should we be expecting from that program in 2024?

Speaker 2

Thanks for that question, Sean, it's a good question. And the answer is, as we've kind of said before, we're really excited about the collaboration. We're really excited about the molecule. Getting complement inhibitors to last several months at therapeutic levels in the eye is a challenge. If it wasn't a challenge, you'd see them already.

Speaker 2

However, we've made great progress and we remain optimistic that we will be able to Sustained release a complement inhibitor. But until we have really are confident in our formulation and our ability to do this consistently, We're not going to make any public statements around that. So I would say that again, we're still working on it. We have made great progress. We have some really great scientists working on this.

Speaker 2

But it's not an easy task to accomplish.

Speaker 1

Yes. Sean, maybe I can add to that because if you look at how we Our cadence on disclosure, we've just disclosed 2,301 this past quarter because we've gotten it to a point where it formulates and we're in a position To move it into those preclinical programs. And I think you should think the same for the complement space as well. Once we get that formulation that we know works and Has the right window. We'll start talking about it a little more publicly on what that pathway looks like.

Speaker 7

Okay. I got you. Thank you. And last one from me is that about the cash runway into 2025, does that include potential Triple III Phase III trials in wet AMD as well now that you're looking to start in second half?

Speaker 1

Yes. Thanks for that question, Sean. So our cash guidance into 2025 includes the ongoing Phase IIs. The planned Phase In DME, which is the VIRONA trial, which will we expect to start in Q1 along with a significant amount of Phase 3 prep To start to be in a position to start the trials sometime second half of next year. It does not include The actual clinical trial cost for the pivotals.

Speaker 1

And as we've talked previously, that's something that we're going to look to A range of options to fund, which includes potential equity raise. We've got strong strategic partner interest and some other levers that we can pull. And we'll be talking about that over the coming months on our plans to fund that really after the Phase 2 results.

Speaker 7

Okay. Thank you again for taking my question.

Speaker 1

Good question. Thank you.

Operator

Thank you so much. Your next Question comes from the line of Yale Jen of Laidlaw and Company. Your line is now open.

Speaker 6

Questions. And my question probably will be focusing on the potential future Phase 3 study. The first one is that in the one of your latest presentations, you have laid out 4 scenarios in terms of the Phase 3 of different BCVA outcomes. I'm just curious based on those assumptions, what might be your thought in terms under each Scenario, what the Phase III study size might be? Then I have a follow-up.

Speaker 6

Yes.

Speaker 1

You're talking about On the BCVA measures? Is that your Right.

Speaker 6

From 1.0 all the way to minus 4.

Speaker 2

Yes. Yale, if I may. Those actually were our Interpretation of the Phase 2 outcomes of where they might land and what they might mean For those outcomes. Without knowing the standard deviation of the change in visual acuity, We can't predict the size of the trials. But you can run it into a statistics package and we've certainly done that.

Speaker 2

If we're minus one letter worse than the EYLEA control and the standard deviation is 7 or less, we could do pivotal trials that might involve as few as 250 to 300 patients. So it's fluid because we don't know those results yet. But there's a second consideration, I think, for most of these trials that when you're doing treatment naive patients When the standard deviation is larger, companies end up doing 500, 600 patient trials. But that's because not only the standard deviation because the FDA requires a certain number of patients for safety. So the FDA requires that you submit and you're able to submit with 1 year efficacy data Half of your second trial, you don't need to 2 year safety to submit.

Speaker 2

But at the 1 year, you need to have 300 patients treated with your go to market dose or higher. Ultimately, you need approximately 400 patients treated with your go to market dose or higher for safety. So that's another consideration for the end of the trial. And that might suggest that we would maybe not do a 1 to 1 to 1 randomization in the pivotal and have more patients in the higher dose to reach those safety measures knowing that the statistics would allow a smaller number. As I've said already, our view is to do this as quickly, as safely, as derisked and as less expensive as possible.

Speaker 2

And that's how we are going to view all the options in the pivotal trials.

Speaker 6

Okay, great. That's very, very helpful. And you mentioned earlier that the Phase 3 also incorporate the retreatment options or the cost. Could you elaborate a little bit more in terms of at least what you proposed the retreatment, any details on that?

Speaker 2

Sure. Yes. Thanks. And we've been I think we've been very consistent from the start. Even though we have in vivo and in vitro evidence that these EYP-nineteen-one inserts will release at therapeutic levels for approximately 9 months.

Speaker 2

We've done enough tox Studies to show that even if we reinject earlier than that, we're in a very safe area for toxicity of virolinib and number of inserts. In fact, we have not found the maximally tolerated level of VIROLINDA with the animal eyes. So from a safety perspective, It's not a problem. Why did we choose 6 months? I think it's simple.

Speaker 2

That's what retina specialists want. They want flexibility to dose drugs when they want to dose them. And while it's clear that some eyes can go longer than 6 months, Remember in our Phase I trial rather, we had a third of the eyes made it a year without supplement. We're going for the label of every 6 months because we want to give the doctors flexibility to dose that often should they choose to.

Speaker 6

Okay, great. That's helpful. And then maybe just add one more that regarding spots From the competitors news this morning, was that something you guys also consider or it still depends?

Speaker 2

Well, yes, again, I think I did address this earlier, but I'll reiterate. We have What we believe is an agreement with the FDA, that's in writing, that we have an acceptable protocol for our pivotal trials. If that is the fastest, least risky way to proceed, that's our plan. And we've seen nothing at this point to alter that. Obviously, it's dependent on good to great data from Dovio 2.

Speaker 2

But there may be Learnings from other companies' approach, and we'll be studying that to see if there are any learnings for us. So until the details are out, I really can't make any comment on that except to reiterate once more, we are very comfortable with where our program is at right now.

Speaker 6

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

Operator

Thank you so much. Your next question comes from the line of Yi Chen of H. C. Wainwright and Company. Your line is now open.

Speaker 8

Thank you for taking my question. So my question is by positioning 19 oh one as a maintenance therapy, Well, your competitor seems to target treatment naive patient in their Phase 3 trial. Does that mean you could potentially lose part of the market in the future? I mean, could you use 1901 For treatment naive patients as well? Thank you.

Speaker 2

So if we get a label for maintenance therapy And the label includes follow use of NK21 after induction with EYLEA or any anti VEGF, let's say hypothetically. I think doctors knowing the retina specialist Community the way I do, I think doctors will try it earlier than after 3 induction doses in some cases. If we're safe, effective and tolerable, I think the argument might be why not use it after a second induction or first induction dose. Will it be used as solo therapy initially? I think data needs To be shown that it's effective that way.

Speaker 2

So again, the market share depends on a lot of things. And Once again, one of the things we just talked about was reinjection. And the hope and expectation is we would get a label for every 6 months reinjection. The FDA was clear that if we wanted to label for reinjection, we needed to test reinjection in the pivotal trials. And so I think that if That is the way our label reads eventually.

Speaker 2

I think that will have an advantage also. So it's hard to predict. I would certainly admit that. But once again, we are very comfortable with where our program is at and the approach that we're taking. And the retina Community that we've talked to I think is in favor of the approach that we're taking.

Speaker 2

And If we get that label, I think retina specialists will figure it out.

Speaker 1

Yes. And maybe if I can add to that, just keep in mind the vast majority of the market is Previously treated patients and the fact that we are going to be able to redose every 6 months is going to be meaningful on our label. And I think ultimately physicians will have the opportunity to use it sooner. But as we think about our approach and the market approach, we're addressing A very significant portion of a $10,000,000,000 plus market. So we're comfortable with our pathway.

Speaker 2

And I could add one more George. That was an excellent point you made about for every newly diagnosed patient, a Reva Specialists probably has a dozen or more previously treated So once again, from a recruitment perspective and from speed to filling trial. There's a lot more maintenance therapy patients out there than there is newly diagnosed and that's one of the many reasons why we've chosen this pathway, speed to approval. Thank

Speaker 3

you.

Speaker 2

Could we see if Colleen is Still on the line and wants to ask a question.

Speaker 1

Yes, she responded. She's having issues on a number of calls this morning. So she will find her later.

Speaker 6

Great.

Operator

All right. And we actually don't have any further questions in the queue at this time. So ladies and gentlemen, thank you for participating in today's conference. This does conclude your webcast on your program. You may now disconnect.

Operator

Everyone, have a great day.

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Earnings Conference Call
EyePoint Pharmaceuticals Q3 2023
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