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spk10: Good morning, my name is Kevin and I'll be your conference operator today. At this time, I'd like to welcome everyone to the iPoint Pharmaceuticals fourth quarter and full year 2023 financial results and recent corporate developments conference call. There will be a question and answer session to follow at the completion of the prepared remarks. Please be advised, this call is being recorded at the company's request. I want to like turn the call over to George Elston, Executive Vice President and Chief Financial Officer of iPoint Pharmaceuticals.
spk05: Thank you, and thank you all for joining us on today's conference call to discuss iPoint Pharmaceuticals' fourth quarter and full year 2023 financial results and recent corporate developments. With me today is Dr. Jay Duker, President and Chief Executive Officer, and Jay will begin with a review of recent corporate updates and discuss the ongoing clinical trials for EYP1901. I will close with commentary on the fourth quarter and full year 2023 financial results. We will then open the call for your questions. Earlier this morning, we issued a press release detailing our financial results and recent operational developments. A copy of the release can be found in the Investor Relations tab on the corporate website, www.ipointpharma.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 of our most recent annual report on Form 10-K, which is on file with the SEC. and in other filings that we may make with the SEC in the future. Any forward-looking statements represent our views as of today only. While we may elect to update these forward-looking statements at some point in the future, we specifically disclaim any obligation to do so, even if our views change. Therefore, you should not rely on these forward-looking statements as representing our views as of any date subsequent to today. I'll now turn the call over to Dr. Jay Duker, President and Chief Executive Officer of iPoint Pharmaceutical.
spk07: Thank you, George. Good morning, everyone, and thank you for joining us. 2023 was truly an exceptional year for iPoint Pharmaceuticals on all fronts. We completed our transformation into a clinical stage biopharmaceutical company with the outlicense of the UT franchise last spring for $82.5 million plus future royalties. We advanced our lead pipeline asset, EYP1901, across three promising indications. wet age-related macular degeneration, or wet AMD, non-proliferative diabetic retinopathy, or NPDR, and diabetic macular edema, or DME. We also significantly strengthened our balance sheet, ending 2023 with $331 million in cash and investments and no debt. This is driven by the UT sale and a $230 million oversubscribed follow-on equity offering. I'd like to review our recent progress for our lead product candidate, EYP1901, a potentially paradigm-altering treatment for patients suffering from VEGF-mediated retinal diseases. In December, we reported positive top-line efficacy and safety data from our Phase II W02 clinical trial in wet AMD, achieving all primary and secondary endpoints. We expect to initiate the first pivotal Phase III wet AMD trial, the Lugano trial, in the second half of this year, with the second pivotal trial, called the Lucia trial, to follow. We also look forward to reporting top-line data for the Phase II PAVEA clinical trial in the second quarter of this year, and top-line data from the Phase II Verona trial in the first quarter of 2025. As a reminder, EYP1901 is an investigational, sustained-release product that consists of a selective and patent-protected tyrosine kinase inhibitor, or TKI, formulated in DuraCert E, the bioerodible version of our proprietary DuraCert technology. Virolinib 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. In addition to the positive safety and efficacy data reported to date, Virolinib has also demonstrated neuroprotection in a validated retinal detachment animal model. Virolinib may also have an antifibrotic effect as it blocks the PDGF receptor. EYP1901 is delivered by an intravitreal injection in the physician's office, similar to the current FDA-approved anti-VEGF biologic treatments. Unlike currently approved biologics and other sustained-release anti-VEGFs in development, EYP1901 is shipped and stored at ambient temperature. Additionally, Virolinib through DuraCert E is immediately bioavailable in the eye, featuring an initial burst of drug followed by our near constant zero-order kinetic release for up to nine months. Our goal is to provide a product that maintains stable vision and retinal anatomy for the majority of wet AMD patients within every six-month label. This could represent a significant improvement compared to the current anti-VEGF treatments that are dosed on average every two months in the United States. And this may allow patients and practitioners the flexibility to reduce the number of visits without sacrificing visual outcomes. Turning to the Phase II W02 non-inferiority clinical trial evaluating EYP1901 in previously treated wet AMD patients as a potential maintenance therapy, All primary and secondary endpoints were achieved in this trial, including a statistically non-inferior change in best corrective visual acuity, or BCVA, versus the aflibricep control for both EYP1901 arms. Non-inferiority change in BCVA is the most commonly used endpoint in wet AMD pivotal trials and subsequent FDA approval. Importantly, EYP1901 continued to demonstrate a favorable safety profile with no EYP1901-related ocular or systemic serious adverse events, or SAEs, reported. We also saw an over 80% reduction in treatment burden measured both prospectively and retrospectively with strong anatomical control in both EYP1901 cohorts. At the angiogenesis meeting in February, investigators reported that a subgroup of W02 patients remained anti-VEGF supplement-free up to six months after delivery of EYP1901. This subgroup demonstrated numerical superiority in change in BCVA, along with strong anatomical control compared to the Aflibricep control group. This result confirms that the positive top-line data from the Phase II W02 trial were driven by EYP1901 and not by supplemental injections. We anticipate initiating the Lugano Phase III trial in wet-empty in the second half of 2024 and the second pivotal trial, Lucia, several months after. The Phase II W02 trial of EYP1901 was designed to mirror the anticipated design of the Phase III trials based on our Type C meeting with the FDA, as well as other interactions. The key differences between W02 and the Phase III trials are that we anticipate that Phase III will feature redosing of EYP1901 every six months, the primary efficacy endpoint will be non-inferior change in BCVA at approximately one year, and the two EYP1901 arms will be one or two inserts versus the two and three inserts used in W02. The decision to use one versus two inserts in the phase three trials is driven by the positive W02 data for both the two milligram and the three milligram doses. The Lugano phase three trial will be conducted largely in the U.S., and the Lucia phase three trial will include U.S. and ex-U.S. sites as we intend to seek EMA approval. We look forward to reviewing our plans at the end of Phase 2 meeting with the FDA in April, and we expect to provide updates after those meeting minutes are received. As I mentioned earlier, we are on track to report top-line data from the Phase 2 PAVEA trial in 2Q of this year. PAVEA is a randomized controlled trial evaluated EYP1901 as a potential nine-month treatment for moderately severe to severe NPDR. The trial enrolled 77 patients who were randomly assigned to one of two doses of EYP1901 or to the control group that received a sham injection. There remains a great unmet need for a safe, efficacious, and convenient treatment for NPDR that proactively reduces the risk of progressing to site-threatening complications over the long term. Approximately 90% of patients with NPDR receive no course of treatment apart from observation by their eye doctors until their disease progresses to DME and or proliferative diabetic retinopathy. This is because the approved treatments are short-acting and therefore require frequent injections. We believe EYP1901 could potentially create a new market for NPDR patients by providing an every-nine-month treatment option that matches a patient's visit cadence. In the PAVEA trial, the primary endpoint is structural. A photograph of the retina is taken on day one of the study and then compared to a photograph taken at month nine. A reading center independently evaluates the photographs to assess the degree of retinopathy on the diabetic retinopathy severity scale, abbreviated the DRSS. The DRSS is a well-validated measure that correlates the functional with the anatomic outcomes. the accepted clinically relevant step change demonstrates a two-step reduction in the scale. In the PAVEA trial, we are looking for at least one-third of the patients to show a greater than or equal to two-step reduction on the DRSS scale at nine months. It's important to note that this is a lower limit and not an expectation. We will also be looking at important secondary endpoints, including reduction in vision-threatening complications, prevention of DME and proliferative diabetic retinopathy, degree of retinal ischemia, and safety. Consistent with our results to date for this program, we expect to see a continued favorable safety profile, a critical factor in any retinal drug. Turning to our third indication, in January, we initiated the Phase II Verona trial, evaluating EYP1901 and a second diabetic eye disease indication, DME, a sight-threatening complication of diabetes that can lead to severe visual loss. Similar to wet AMD, this is a VEGF-mediated disease where there is a significant need for differentiated and longer-acting treatments. Verona is a randomized controlled single-masked Phase II trial of EYP1901 in DME patients previously treated with standard-of-care anti-VEGF therapy. The three-arm trial is expected to enroll approximately 25 patients randomized to one of two doses of EYP1901 or an afibrocept control. The primary efficacy endpoint of the Verona trial is time to first anti-VEGF supplement, up to 24 weeks, based on established criteria. Secondary endpoints include safety, change in BCVA, change in central subfield thickness as measured on OCT, and change in DRSS over time. We remain on track to report top-line data from the Verona trial in the first quarter of 2025. We remain highly encouraged by the growing body of positive clinical data for EYP1901, and we are optimistic that EYP1901 has the potential to change the current treatment paradigm for VEGF-mediated retinal diseases. Turning to our pipeline programs, we announced a new preclinical program, EYP2301, which delivers a promising TIE2 agonist, raciprotafib, formerly known as AKB9778, formulated into RICERT-E. Raciprotafib is an inhibitor of vascular endothelial protein tyrosine phosphatase, or VEPTP. We believe that delivering EYP2301 intravitrally has the potential to offer new site-saving treatment for patients with severe retinal disease, either alone or in combination with anti-VEGFs. We continue to evaluate additional molecules for sustained delivery in DuraCert E, including complement inhibition, and rare diseases, and hope to update you on these programs later this year. Last, I'm delighted to welcome Ramiro Ribeiro, MD, PhD, to iPoint as our new chief medical officer. Dr. Ribeiro is a trained retinal specialist who joins us from Apellis Pharmaceuticals, where he served as vice president, head of clinical development. And we're confident that his proven leadership and strong scientific and clinical background will be a tremendous asset to the iPoint team. I'd like to thank Dr. Dario Pacerino, who served as our chief medical officer for the past seven years. To close, I want to thank the entire I-Point team for an incredible 2023 and a strong start in 2024. The impressive execution and dedication demonstrated by our team to reach these milestones reflects the entire organization's commitment to patients. In addition, I'd like to thank the patients and clinical investigators for their participation in the ongoing trials. Without you all, the progress we've made advancing EYP1901 would not be possible. With our compelling clinical pipeline representing potential multibillion-dollar product opportunities, our best-in-class sustained ocular delivery to research E technology, along with a strong balance sheet, we're well-positioned to grow as a leader in ocular drug delivery and to bring 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.
spk05: Before we review the financial results, 2023 was an exceptional year for our financial performance. As Jay noted, we ended 23 with a strong balance sheet driven by the outlicense of UTEEQ, the retirement of outstanding bank debt, and an oversubscribed $230 million follow-on financing in December, resulting in $331 million of cash investments at December 31st. As the financial results for the three months and full year ended December 31st, 2023, were included in the press release issued this morning, my comments today will be focused on the high level review for the quarter. For the quarter ended December 31st, 2023, total net revenue was 14 million compared to 10.5 million for the quarter ended December 31st, 2022. Net product revenue for the quarter ended December 31st, 2023 was 0.7 million compared to net product revenue for the quarter ended December 31st, 2022 of 9.9 million. This decrease in net product revenue resulted from our strategic exit from the commercial business in the first half of 2023, highlighted by the outlicense of UTEEQ in May. Net revenue from royalties and collaboration for the quarter ended December 31, 2023, totaled $13.3 million, compared to $0.6 million in the corresponding period in 2022. The increase was primarily due to partial recognition of deferred revenue from the license of the UTEEQ franchise, which began in the second quarter of 2023 and will be recognized over a two-year period in connection with the delivery of UTEEK supply units. Operating expenses for the quarter ended December 31st, 2023 totaled $30.4 million compared to $54.3 million in the prior year period. This decrease was primarily driven by the strategic exit from the commercial business in the first half of 2023 and a one-time intangible asset impairment charge in the fourth quarter of 2022. Non-operating income totaled $2.3 million, and net loss was $14.1 million, or $0.33 per share loss, compared to a net loss of $43.5 million, or $1.16 per share loss, for the prior year period. Turning to the full year end of December 31, 2023, Total net revenue was $46 million compared to $41.4 million for the year ended December 31, 2022. Net product revenue for the full year ended December 31, 2023 was $14.2 million compared to net product revenues for the full year ended December 31, 2022 of $39.9 million. Net revenue from royalties and collaborations for the full year ended December 31, 2023 totaled $31.8 million compared to $1.5 million in the corresponding period in 2022. Operating expenses for the full year ended December 31, 2023 totaled $121.1 million versus $141 million in the prior year period. Net non-operating expense totaled $4.4 million and net loss was $70.8 million or $1.82 per share compared to a net loss of 102.3 million or $2.74 per share for the prior year period. Cash and investments in marketable securities on December 31st, 2023 totaled 331.1 million compared to 144.6 million as of December 31st, 2022. We expect the cash and investments on December 31st, 2023 will fund us through top-line data for the planned Phase III clinical trials of EYP1901 for wet AMD in 2026. This also includes completion of the ongoing Phase II clinical trials for EYP1901 in wet AMD and PDR and DME. In conclusion, we are pleased with iPoint's progress in 2023 and are well-capitalized to advance our product pipeline to key value inflection points. I'll now turn the call back over to Jay for closing remarks.
spk07: Thank you, George. As we discussed, I-Point is a story of execution and positive data. We've accomplished our clinical milestones efficiently and on track with our guidance, and we plan to continue this track record in 2024 and beyond. Key upcoming catalysts include top-line data from our Phase 2 PAVEA clinical trial in the second quarter of 2024, an end-of-Phase 2 meeting with the US FDA in April, and initiation of the first non-inferiority pivotal Phase III Lugano trial of EYP1901 in wet AMD in the United States in the second half of this year. Enrollment completion of the Phase II Verona clinical trial of EYP1901 in DME, with top-line data expected in the first quarter of 2025, and earlier-stage pipeline program advancement towards clinical development. This remains an incredibly exciting time for iPoint, 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 very much for listening this morning. I will now turn it over to the operator for questions.
spk10: Thank you. Ladies and gentlemen, if you have a question or a comment at this time, please press star 1-1 on your telephone. If your question has been answered and you wish to move yourself from the queue, please press star 1-1 again And in the interest of time and to accommodate everybody in the question queue, we ask that you limit yourself to one question. We'll pause for a moment while we compile our Q&A roster.
spk09: Our first question comes from Tess Romero with JP Morgan.
spk10: Your line is open.
spk00: Hello. Good morning, guys. Thanks for taking our question. As you think about the potential opportunity for EYP 1901, Are you able to provide a little bit of further context around how you think about further segmenting the NPDR population? And out of the 6 million NPDR patients here in the U.S., which patients do you see as the more low-hanging fruit for potential therapy? Thank you.
spk07: Thank you, Tess. Before I get to the answer, I'd just like to take this opportunity to introduce our new CMO, Dr. Ramiro Ribeiro, who's here with George and Iveson.
spk12: Thanks, Jay. First, I want to say that I'm very privileged to join the iPOINT team. I'm a retina specialist by training. After working private practice, I moved to the U.S. as part of my Ph.D. program, where I really felt in love with research. After some time in the academic setting, I transitioned to biotech, mainly small biotech, but always in ophthalmology. I spent time at Optotech doing the Forvisa trial for YTMD at Acucela doing a staggered disease. And recently, I was the head of clinical development at Appellus, where I led the clinical team from the inception of the phase three protocol, execution of the global trials, regulatory submission, and last year, the approval of Cyphovri, the first therapy for GH. I joined EyePoint for three reasons. First, because I believe in the technology that will bring options for patients with asthma conditions. Second, the strong and very convincing results from W2. And lastly, the retina community is very small and EyePoint has a reputation of being a strong scientific company and always put patients in the first place.
spk07: Thanks, Romero. And Tess, back to your question, I think the obvious answer is that eyes that have the most severe NPDR are the logical first group that clinicians might treat because those are eyes that have high risk to go on to site-threatening complications like DME and PDR. By preventing or at least delaying significantly the advancement to those site-threatening complications. Using EYP1901 potentially once every nine months approximately, we think we can really improve patients' lives by preventing visual loss and preventing the eventual need for multiple injections over years.
spk09: Thank you. One moment for our next question.
spk10: Our next question comes from Tyler Van Buren with TD Cowan. Your line is open.
spk08: Great. Thanks. Good morning. Congratulations on all the progress during the quarter. For the plans and a phase two meeting with the FDA next month regarding your phase three plan, can you elaborate on the key discussion topics and to what extent you discussed your development strategy prior to initiating W-2 as we think about the interactions you've already had with the FDA?
spk07: Yeah, thanks, Tyler. So, the second part of your question, I think I'll answer first, which is the sharing and discussion of our development plans with the FDA. As we've said in the past, there was considerable discussion within the company and with the agency several years ago to go straight from our Phase 1 Davio trial into pivotal trials in wet AMD. As a result of that discussion, we had a Type C meeting with the FDA and further discussion after the Type C meeting, at which point the agency and the company had reached a general, let's call it an agreement, over the protocol for potential Phase III. We then made the strategic decision to do a more, I'd say, traditional phase two program prior to the phase three. Of course, that was the W-2 program. And we took the agency's advice, instructions, learnings from the end of phase two meeting and subsequent communications and developed the protocol for W-2 out of those discussions. And therefore, we're optimistic, and I'd say going into the end of phase two, meeting confident about most of the large touch points around our pivotal trial design. So in the first part of the question, you asked about key topics. I'm not sure that I can point to anything in particular as a key topic. We're going to, again, seek general agreement on a non-inferiority trial with a minus 4.5 non-inferiority margin. All of this is kind of standard and was restated clearly in the draft guidelines. So I'm not sure those kind of issues really bubble up to use the term key. We have some other questions around some inclusion-exclusion criteria, which will hopefully be made clear in the meeting, and also some issues around the safety cohort that we need to show the FDA. But again, I'm optimistic that these will all be straightforward and relatively simple for the agency and us to come to agreement on.
spk09: Thank you. One moment for our next question. Our next question comes from Yatin Sanecha with Guggenheim. Your line is open.
spk01: Hey, guys. Thank you for taking my question. Quick one for me, or this is more of a clarification on NPDR. Jay, you've talked about, you know, that, you know, if you see about 30%, 35% response, you'll move forward. But if you look at the data from You know, VEGFs, they are in the 45% to 50% range. So I'm just curious, like, what you heard from the community, like, why you move forward at that level. And then also, in this particular study, are you also looking at the BCVA? I apologize if you already commented on that, but curious to understand how the BCVA dynamic should be measured and what the expectations there are.
spk07: Sure, Jatin. Thanks for the questions. So that kind of floor, I would say, for step improvement in the DRSS for our NPDR trial is really based on what many of the KOLs and doctors in the community have told us, that if our drug is safe and effective and can be dosed perhaps every nine months, they would use it in a considerable number of their NPDR patients if there was even a one out of three rate of improvement. The rate of improvement that the current approved therapies show, 50%, 60%, 70%, I have to say it's great, but it's almost irrelevant because there have to be given so frequently that practitioners and patients really are to a large degree participating. The other thing about NPDR, while there isn't an immediate feedback with a biomarker to the clinician as to whether your drug is working or not, the clinicians are able over time to reevaluate the degree of diabetic retinopathy in NEI and make their assessment in the office of whether that patient is benefiting from the therapy or isn't. So if you have a safe, effective, bio-erodible therapy and it isn't working, then the clinicians could simply not repeat it. So we do think that we're going to be able to work with the community to find the best patients for the treatment and help them decide whether continued treatment is in the patient's best interest. As for BCVA, it's not a primary endpoint. Most of these NPDR patients have relatively good best corrected visual acuity. And NPDR in and of itself, unless there's quite a bit of macular ischemia involved in it, typically retain good vision. So it's something that we were obviously measuring, but we don't expect significant changes in BCVA in either the treatment or the control arms.
spk09: Thank you. One moment for our next question.
spk10: Our next question comes from Jennifer Kim with Cantor Fitzgerald. Your line is open.
spk17: Hey, guys. Thanks for taking my question, and Dr. Ribeiro, glad to see another retina guy on the team. Maybe to touch up on the last question, since NPDR is around the corner, what do you think is the most important read-through from the NPDR study to the DME study, given the differences in endpoints and the payload of the inserts and the different duration of therapy? And I guess, ultimately, what kind of profile or other market dynamics are you assuming when you talk about modeling a potential, like, billion-dollar-plus opportunity in DR and DME? Thanks.
spk07: Thanks, Jennifer. So, I think the number one read-through is, up until the PAVEA trial, we hadn't dosed EYP1901 in a diabetic population. And so, obviously, we're looking for some, you know, basic, you know, acknowledgements that in this population that has a VEGF-mediated disease that our inserts work and are safe. And I can just remind everybody that we did release interim safety data as of last November in the PAVEA trial, and we had no virulence or EYP1901-related ocular systemic complications. So the read-through primarily will be, you know, can we show a benefit in this particular disease? DME is an extension of NPDR, just like PDR is an extension. As eyes get more ischemic and presumably VEGF levels and other cytokine levels go up higher, that's when you start to see this type of leakage in new blood vessels. And therefore, I think if we can show in the NPDR population that we are making a biological improvement, I think there'll be definitely read through the DME. As to the differences in the studies and the insert payloads, shouldn't matter. Insert payloads, you know, again, they release almost identically. They give levels that are consistent with the payload as opposed to, you know, the difference in the actual inserts. So I don't think those particular aspects of the differences between the Verona trial and the Pavia trial will be of any significance at all.
spk09: Thank you. One moment for our next question. Our next question comes from Greg Civenge with Mizzou Health Securities.
spk10: Your line is open.
spk18: Good morning. Thank you for taking my question. I was curious, in light of the data that you presented in WET-AMD and in the time since, Have you been able to do any perhaps new market research with either clinicians or payers on their reactions? And if you have, what were the findings? And if you haven't done any, maybe you could just provide us a general big picture comment around what the feedback from the retinal specialist community has been. Thank you.
spk07: Thanks, Greg. It's a great question. And while I would say the formal aspects of both market research for both payers and practitioners is ongoing, and since it is ongoing, I really can't comment on how the new data has changed in a quantitative, formal way, what the practitioners and the payers are thinking about EYP1901. I can say again in a rather qualitative way, the initial interactions we have with the payers are quite positive, and the practitioners the same. Again, the data from W02 was excellent. We had essentially no change in visual acuity over the six months after our inserts went in compared to the idea of control, and we did it with a really intact safety record in anatomic data that really went along with the visual acuity data. So as the retina community is exposed to not only the initial data set, but the subsequent subset analysis, I think the enthusiasm amongst the potential for this is definitely growing. And in a recent conference, I think when polled of the new agents that are available, the polled retina specialists put EYP1901 as the most exciting. So I think our message and our great data is getting out there, and I think it will continue to be well received in both those communities.
spk10: Thank you. One moment for our next question. Our next question comes from Colleen Cussie with VAIR. Your line is open.
spk16: Great. Thanks. Good morning. Thanks for taking our questions. On the what AMD phase 3 design, maybe this is something that you'll get more feedback on in your FDA meeting, but can you talk about your understanding of the role of the low-dose arm in the pivotal study design? Do you need to be better than the low-dose, or is that just for masking purposes? And if you do have to be better, is that statistically significantly better or just a favorable trend?
spk07: Thanks. Yeah, thanks, Colleen. So, in our interactions with the FDA, the second arm of our drug was viewed as a way to improve the masking in the study. There was never any indication or suggestion that the lower dose had to perform necessarily any different than the higher dose. However, as we've talked about, the second reason we want to use two doses is that there was no dose response in Davio2. Two milligrams and three milligrams worked essentially equivalently. And therefore, we want the opportunity to test the dose that's around two milligrams And another dose that's possibly lower, that would a dose be delivered by a single insert. And we hope to and expect to power the trial enough that the lower dose could show non-inferiority against the afibrocept control group.
spk09: Thank you. One moment for our next question. Our next question comes from Yale Jen with Laidlaw and Company. Your line is open.
spk02: Good morning. Thanks for taking the question. Just for the DME, I know it's probably a little bit later to happen. And in terms of 1901, what its role could play any differently in terms of the potential paradigm differences between the DME and with the wet AMD?
spk07: Thanks, Yael. That's a really good question, and it speaks to the differentiation in the two diseases of how they respond to anti-VEGFs. DMV patients do respond to anti-VEGFs, but the anatomic response is often delayed and takes multiple injections to actually see that response. Therefore, a sustained release insert like EYP1901 might not show a response faster than an anti-VEGF, but we would expect and hope that if the population of diabetics responds the same way that the wet AMD population responds, that we can show a similar benefit to other anti-VEGF agents with a significantly reduced treatment burden. That would be the goal.
spk09: Thank you. One moment for our next question. Our next question comes from Yu Chen with H. Lee Wainwright. Your line is open.
spk19: Thank you for taking my question. Could you provide us with your view on gene therapy being developed for YMD, whether they could be a big competitor for six months or nine months, cysteine therapy for YMD, and whether their application could be limited to most severe patients? Thank you.
spk07: Thanks, Yi. So gene therapy is certainly an exciting advance in the retina field. as a replacement for a faulty gene. It's obviously been approved in that indication and really has been an incredible benefit to patients. Using it as a drug delivery also shows promise, especially for chronic diseases. The issues around wet AMD really have to do with, first of all, what appears to be a relatively narrow therapeutic window between efficacy and safety that the gene therapies need to really thread. And secondly, the question about alternatives. You know, gene therapy is presumably going to be more expensive than current therapies or other therapies in development. And therefore, how does one, you know, either an individual retina specialist or payers or society in general justify the use of a more expensive type treatment if it's not clearly superior to what's out there already? So at a high level, I think all retina specialists are excited about the promise of gene therapy, but in way in particular, there's a really tight needle that needs to be threaded.
spk10: Thank you. And I'm showing no further questions at this time. Ladies and gentlemen, thank you for participating in today's conference. This does conclude your program. You may now disconnect. Everyone have a great day. Everyone. Thank you. you Thank you. Thank you. you you
spk09: Good morning. My name is Kevin, and I'll be your conference operator today.
spk10: At this time, I'd like to welcome everyone to the iPoint Pharmaceuticals fourth quarter and full year 2023 financial results and recent corporate developments conference call. There will be a question and answer session to follow at the completion of the prepared remarks. Please be advised, this call is being recorded at the company's request. I would like to turn the call over to George Elston, Executive Vice President and Chief Financial Officer of iPoint Pharmaceuticals.
spk05: Thank you, and thank you all for joining us on today's conference call to discuss iPoint Pharmaceuticals' fourth quarter and full year 2023 financial results and recent corporate developments. With me today is Dr. Jay Duker, President and Chief Executive Officer, and Jay will begin with a review of recent corporate updates and discuss the ongoing clinical trials for EYP1901. I will close with commentary on the fourth quarter and full year 2023 financial results. We will then open the call for your questions. Earlier this morning, we issued a press release detailing our financial results and recent operational developments. A copy of the release can be found in the Investor Relations tab on the corporate website, www.ipointpharma.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 of our most recent annual report on Form 10-K, which is on file with the SEC. and in other filings that we may make with the SEC in the future. Any forward-looking statements represent our views as of today only. While we may elect to update these forward-looking statements at some point in the future, we specifically disclaim any obligation to do so, even if our views change. Therefore, you should not rely on these forward-looking statements as representing our views as of any date subsequent to today. I'll now turn the call over to Dr. Jay Duker, President and Chief Executive Officer of iPoint Pharmaceutical.
spk07: Thank you, George. Good morning, everyone, and thank you for joining us. 2023 was truly an exceptional year for iPoint Pharmaceuticals on all fronts. We completed our transformation into a clinical stage biopharmaceutical company with the outlicense of the UT franchise last spring for $82.5 million plus future royalties. We advanced our lead pipeline asset, EYP1901, across three promising indications. wet age-related macular degeneration, or wet AMD, non-proliferative diabetic retinopathy, or NPDR, and diabetic macular edema, or DME. We also significantly strengthened our balance sheet, ending 2023 with $331 million in cash and investments and no debt. This is driven by the UT sale and a $230 million oversubscribed follow-on equity offering. I'd like to review our recent progress for our lead product candidate, EYP1901, a potentially paradigm-altering treatment for patients suffering from VEGF-mediated retinal diseases. In December, we reported positive top-line efficacy and safety data from our Phase II W02 clinical trial in wet AMD, achieving all primary and secondary endpoints. We expect to initiate the first pivotal Phase III wet AMD trial, the Lugano trial, in the second half of this year, with the second pivotal trial, called the Lucia trial, to follow. We also look forward to reporting top-line data for the Phase II PAVEA clinical trial in the second quarter of this year, and top-line data from the Phase II Verona trial in the first quarter of 2025. As a reminder, EYP1901 is an investigational, sustained-release product that consists of a selective and patent-protected tyrosine kinase inhibitor, or TKI, formulated in Duracert E, the bioerodible version of our proprietary Duracert technology. Virolinib 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. In addition to the positive safety and efficacy data reported to date, Virolinib has also demonstrated neuroprotection in a validated retinal detachment animal model. Virolinib may also have an antifibrotic effect as it blocks the PDGF receptor. EYP1901 is delivered by an intravitreal injection in the physician's office, similar to the current FDA-approved anti-VEGF biologic treatments. Unlike currently approved biologics and other sustained-release anti-VEGFs in development, EYP1901 is shipped and stored at ambient temperature. Additionally, Virolinib through DuraCert E is immediately bioavailable in the eye, featuring an initial burst of drug followed by our near-constant zero-order kinetic release for up to nine months. Our goal is to provide a product that maintains stable vision and retinal anatomy for the majority of wet AMD patients within every six-month label. This could represent a significant improvement compared to the current anti-VEGF treatments that are dosed on average every two months in the United States. And this may allow patients and practitioners the flexibility to reduce the number of visits without sacrificing visual outcomes. Turning to the Phase II W02 non-inferiority clinical trial evaluating EYP1901 in previously treated wet AMD patients as a potential maintenance therapy, All primary and secondary endpoints were achieved in this trial, including a statistically non-inferior change in best corrective visual acuity, or BCVA, versus the afib-recept control for both EYP1901 arms. Non-inferiority change in BCVA is the most commonly used endpoint in wet AMD pivotal trials and subsequent FDA approval. Importantly, EYP1901 continued to demonstrate a favorable safety profile with no EYP1901-related ocular or systemic serious adverse events, or SAEs, reported. We also saw an over 80% reduction in treatment burden measured both prospectively and retrospectively with strong anatomical control in both EYP1901 cohorts. At the angiogenesis meeting in February, investigators reported that a subgroup of W02 patients remained anti-VEGF supplement-free up to six months after delivery of EYP1901. This subgroup demonstrated numerical superiority in change in BCVA, along with strong anatomical control compared to the Aflibricep control group. This result confirms that the positive top-line data from the Phase II W02 trial were driven by EYP1901 and not by supplemental injections. We anticipate initiating the Lugano Phase III trial in wet-empty in the second half of 2024 and the second pivotal trial, Lucia, several months after. The Phase II W02 trial of EYP1901 was designed to mirror the anticipated design of the Phase III trials based on our Type C meeting with the FDA, as well as other interactions. The key differences between W02 and the Phase III trials are that we anticipate that Phase III will feature redosing of EYP1901 every six months, the primary efficacy endpoint will be non-inferior change in BCVA at approximately one year, and the two EYP1901 arms will be one or two inserts versus the two and three inserts used in W02. The decision to use one versus two inserts in the phase three trials is driven by the positive W02 data for both the two milligram and the three milligram doses. The Lugano phase three trial will be conducted largely in the U.S., and the Lucia phase three trial will include U.S. and ex-U.S. sites as we intend to seek EMA approval. We look forward to reviewing our plans at the end of Phase 2 meeting with the FDA in April, and we expect to provide updates after those meeting minutes are received. As I mentioned earlier, we are on track to report top-line data from the Phase 2 PAVEA trial in 2Q of this year. PAVEA is a randomized controlled trial evaluated EYP1901 as a potential nine-month treatment for moderately severe to severe NPDR. The trial enrolled 77 patients who were randomly assigned to one of two doses of EYP1901 or to the control group that received a sham injection. There remains a great unmet need for a safe, efficacious, and convenient treatment for NPDR that proactively reduces the risk of progressing to site-threatening complications over the long term. Approximately 90% of patients with NPDR receive no course of treatment apart from observation by their eye doctors until their disease progresses to DME and or proliferative diabetic retinopathy. This is because the approved treatments are short-acting and therefore require frequent injections. We believe EYP1901 could potentially create a new market for NPDR patients by providing an every-nine-month treatment option that matches a patient's visit cadence. In the PAVEA trial, the primary endpoint is structural. A photograph of the retina is taken on day one of the study and then compared to a photograph taken at month nine. A reading center independently evaluates the photographs to assess the degree of retinopathy on the diabetic retinopathy severity scale, abbreviated the DRSS. The DRSS is a well-validated measure that correlates the functional with the anatomic outcomes. the accepted clinically relevant step change demonstrates a two-step reduction in the scale. In the PAVEA trial, we are looking for at least one-third of the patients to show a greater than or equal to two-step reduction on the DRSS scale at nine months. It's important to note that this is a lower limit and not an expectation. We will also be looking at important secondary endpoints, including reduction in vision-threatening complications, prevention of DME and proliferative diabetic retinopathy, degree of retinal ischemia, and safety. Consistent with our results to date for this program, we expect to see a continued favorable safety profile, a critical factor in any retinal drug. Turning to our third indication, in January, we initiated the Phase II Verona trial, evaluating EYP1901 and a second diabetic eye disease indication, DME. a sight-threatening complication of diabetes that can lead to severe visual loss. Similar to wet AMD, this is a VEGF-mediated disease where there is a significant need for differentiated and longer-acting treatments. Verona is a randomized controlled single-masked Phase II trial of EYP1901 in DME patients previously treated with standard-of-care anti-VEGF therapy. The three-arm trial is expected to enroll approximately 25 patients randomized to one of two doses of EYP1901 or an Aflibricep control. The primary efficacy endpoint of the Verona trial is time to first anti-VEGF supplement, up to 24 weeks, based on established criteria. Secondary endpoints include safety, change in BCVA, change in central subfield thickness as measured on OCT, and change in DRSS over time. We remain on track to report top line data from the Verona trial in the first quarter of 2025. We remain highly encouraged by the growing body of positive clinical data for EYP1901, and we are optimistic that EYP1901 has the potential to change the current treatment paradigm for VEGF-mediated retinal diseases. Turning to our pipeline programs, we announced a new preclinical program, EYP2301, which delivers a promising TIE2 agonist, Raziprotafib, formerly known as AKB9778, formulated into RICERT-E. Raciprotafib is an inhibitor of vascular endothelial protein tyrosine phosphatase, or VEPTP. We believe that delivering EYP2301 intravitrally has the potential to offer new site-saving treatment for patients with severe retinal disease, either alone or in combination with anti-VEGFs. We continue to evaluate additional molecules for sustained delivery in DuraCert E, including complement inhibition, and rare diseases, and hope to update you on these programs later this year. Last, I'm delighted to welcome Ramiro Ribeiro, MD, PhD, to iPoint as our new chief medical officer. Dr. Ribeiro is a trained retinal specialist who joins us from Apellis Pharmaceuticals, where he served as vice president, head of clinical development. And we're confident that his proven leadership and strong scientific and clinical background will be a tremendous asset to the iPoint team. I'd like to thank Dr. Dario Pacerino, who served as our chief medical officer for the past seven years. To close, I want to thank the entire I-Point team for an incredible 2023 and a strong start in 2024. The impressive execution and dedication demonstrated by our team to reach these milestones reflects the entire organization's commitment to patients. In addition, I'd like to thank the patients and clinical investigators for their participation in the ongoing trials. Without you all, the progress we've made advancing EYP1901 would not be possible. With our compelling clinical pipeline representing potential multibillion-dollar product opportunities, our best-in-class sustained ocular delivery to research E technology, along with a strong balance sheet, we're well-positioned to grow as a leader in ocular drug delivery and to bring 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.
spk05: Before we review the financial results, 2023 was an exceptional year for our financial performance. As Jay noted, we ended 23 with a strong balance sheet driven by the outlicense of UTEEQ, the retirement of outstanding bank debt, and an oversubscribed $230 million follow-on financing in December, resulting in $331 million of cash investments at December 31st. As the financial results for the three months and full year ended December 31st, 2023, were included in the press release issued this morning, my comments today will be focused on the high level review for the quarter. For the quarter ended December 31st, 2023, total net revenue was 14 million compared to 10.5 million for the quarter ended December 31st, 2022. Net product revenue for the quarter ended December 31st, 2023 was 0.7 million compared to net product revenue for the quarter ended December 31st, 2022 of 9.9 million. This decrease in net product revenue resulted from our strategic exit from the commercial business in the first half of 2023, highlighted by the outlicense of UTEEQ in May. Net revenue from royalties and collaboration for the quarter ended December 31, 2023, totaled $13.3 million, compared to $0.6 million in the corresponding period in 2022. The increase was primarily due to partial recognition of deferred revenue from the license of the UTEEQ franchise, which began in the second quarter of 2023 and will be recognized over a two-year period in connection with the delivery of UTIC supply units. Operating expenses for the quarter ended December 31st, 2023 totaled $30.4 million compared to $54.3 million in the prior year period. This decrease was primarily driven by the strategic exit from the commercial business in the first half of 2023 and a one-time intangible asset impairment charge in the fourth quarter of 2022. Non-operating income totaled $2.3 million, and net loss was $14.1 million, or $0.33 per share loss, compared to a net loss of $43.5 million, or $1.16 per share loss, for the prior year period. Turning to the full year end of December 31, 2023, Total net revenue was $46 million compared to $41.4 million for the year ended December 31, 2022. Net product revenue for the full year ended December 31, 2023 was $14.2 million compared to net product revenues for the full year ended December 31, 2022 of $39.9 million. Net revenue from royalties and collaborations for the full year ended December 31, 2023 totaled $31.8 million compared to $1.5 million in the corresponding period in 2022. Operating expenses for the full year ended December 31, 2023 totaled $121.1 million versus $141 million in the prior year period. Net non-operating expense totaled $4.4 million and net loss was $70.8 million or $1.82 per share compared to a net loss of 102.3 million or $2.74 per share for the prior year period. Cash and investments in marketable securities on December 31st, 2023 totaled 331.1 million compared to 144.6 million as of December 31st, 2022. We expect the cash and investments on December 31st, 2023 will fund us through top-line data for the planned Phase III clinical trials of EYP1901 for wet AMD in 2026. This also includes completion of the ongoing Phase II clinical trials for EYP1901 in wet AMD and PDR and DME. In conclusion, we are pleased with iPoint's progress in 2023 and are well-capitalized to advance our product pipeline to key value inflection points. I'll now turn the call back over to Jay for closing remarks.
spk07: Thank you, George. As we discussed, I-Point is a story of execution and positive data. We've accomplished our clinical milestones efficiently and on track with our guidance, and we plan to continue this track record in 2024 and beyond. Key upcoming catalysts include top-line data from our Phase II PAVEA clinical trial in the second quarter of 2024, an end-of-Phase II meeting with the US FDA in April, and initiation of the first non-inferiority pivotal Phase III Lugano trial of EYP1901 in wet AMD in the United States in the second half of this year. Enrollment completion of the Phase II Verona clinical trial of EYP1901 in DME, with top-line data expected in the first quarter of 2025, and earlier-stage pipeline program advancement towards clinical development. This remains an incredibly exciting time for iPoint, 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 very much for listening this morning. I will now turn it over to the operator for questions.
spk10: Thank you. Ladies and gentlemen, if you have a question or a comment at this time, please press star 1-1 on your telephone. If your question has been answered and you wish to move yourself from the queue, please press star 1-1 again And in the interest of time, and to accommodate everybody in the question queue, we ask that you limit yourself to one question. We will pause for a moment while we compile our Q&A roster.
spk09: Our first question comes from Tess Romero with JP Morgan.
spk10: Your line is open.
spk00: Hello. Good morning, guys. Thanks for taking our question. As you think about the potential opportunity for EYP 1901, Are you able to provide a little bit of further context around how you think about further segmenting the NPDR population? And out of the 6 million NPDR patients here in the U.S., which patients do you see as the more low-hanging fruit for potential therapy? Thank you.
spk07: Thank you, Tess. Before I get to the answer, I'd just like to take this opportunity to introduce our new CMO, Dr. Ramiro Ribeiro, who's here with George and Iveson.
spk12: Thanks, Jay. First, I want to say that I'm very privileged to join the iPOINT team. I'm a retina specialist by training. After working private practice, I moved to the U.S. as part of my Ph.D. program, where I really felt in love with research. After some time in the academic setting, I transitioned to biotech, mainly small biotech, but always in ophthalmology. I spent time at Optotech doing the Forvisa trial for YTMD at Acucela doing a staggered disease. And recently, I was the head of clinical development at Appellus, where I led the clinical team from the inception of the phase three protocol, execution of the global trials, regulatory submission, and last year, the approval of Cyphovri, the first therapy for GH. I joined EyePoint for three reasons. First, because I believe in the technology that will bring options for patients with asthma conditions. Second, the strong and very convincing results from W2. And lastly, the retina community is very small and EyePoint has a reputation of being a strong scientific company and always put patients in the first place.
spk07: Thanks, Romero. And Tess, back to your question. I think the obvious answer is that eyes that have the most severe NPDR are the logical first group that clinicians might treat because those are eyes that have high risk to go on to site-threatening complications like DME and PDR. By preventing or at least delaying significantly the advancement to those site-threatening complications. Using EYP1901 potentially once every nine months approximately, we think we can really improve patients' lives by preventing visual loss and preventing the eventual need for multiple injections over years.
spk10: Thank you. One moment for our next question. Our next question comes from Tyler Van Buren with TD Cowan. Your line is open.
spk08: Great. Thanks. Good morning. Congratulations on all the progress during the quarter. For the plans and a phase two meeting with the FDA next month regarding your phase three plan, can you elaborate on the key discussion topics and to what extent you discussed your development strategy prior to initiating W-2 as we think about the interactions you've already had with the FDA?
spk07: Yeah, thanks, Tyler. So, the second part of your question, I think I'll answer first, which is the sharing and discussion of our development plans with the FDA. As we've said in the past, there was considerable discussion within the company and with the agency several years ago to go straight from our Phase 1 Davio trial into pivotal trials in wet AMD. As a result of that discussion, we had a Type C meeting with the FDA and further discussion after the Type C meeting, at which point the agency and the company had reached a general, let's call it an agreement, over the protocol for potential Phase III. We then made the strategic decision to do a more, I'd say, traditional phase two program prior to the phase three. Of course, that was the W-2 program. And we took the agency's advice, instructions, learnings from the end of phase two meeting and subsequent communications and developed the protocol for W-2 out of those discussions. And therefore, we're optimistic, and I'd say going into the end of phase two, meeting confident about most of the large touch points around our pivotal trial design. So in the first part of the question, you asked about key topics. I'm not sure that I can point to anything in particular as a key topic. We're going to, again, seek general agreement on a non-inferiority trial with a minus 4.5 non-inferiority margin. All of this is kind of standard and was restated clearly in the draft guidelines. So, I'm not sure those kind of issues really bubble up to use the term key. We have some other questions around some inclusion-exclusion criteria, which will hopefully be made clear in the meeting, and also some issues around the safety cohort that we need to show the FDA. But again, I'm optimistic that these will all be straightforward and relatively simple for the agency and us to come to agreement on.
spk09: Thank you. One moment for our next question. Our next question comes from Yatin Sanecha with Guggenheim. Your line is open.
spk01: Hey, guys. Thank you for taking my question. Quick one for me, or this is more of a clarification on NPDR. Jay, you've talked about, you know, that, you know, if you see about 30%, 35% response or there, you move forward. But if you look at the data from You know, VEGFs, they are in the 45% to 50% range. And just curious, like, what you heard from the community, like, why you move forward at that level. And then also, in this particular study, are you also looking at the BCVA? I apologize if you already commented on that, but curious to understand how the BCVA dynamic should be measured and what the expectations there are.
spk07: Sure, Jatin. Thanks for the questions. So that kind of floor, I would say, for step improvement in the DRSS for our NPDR trial is really based on what many of the KOLs and doctors in the community have told us, that if our drug is safe and effective and can be dosed perhaps every nine months, they would use it in a considerable number of their NPDR patients if there was even a one out of three rate of improvement. The rate of improvement that the current approved therapies show, 50%, 60%, 70%, I have to say it's great, but it's almost irrelevant because there have to be given so frequently that practitioners and patients really are to a large degree participating. The other thing about NPDR, while there isn't an immediate feedback with a biomarker to the clinician as to whether your drug is working or not, the clinicians are able over time to reevaluate the degree of diabetic retinopathy in NEI and make their assessment in the office of whether that patient is benefiting from the therapy or isn't. So if you have a safe, effective, bio-erodible therapy and it isn't working, then the clinicians could simply not repeat it. So we do think that we're going to be able to work with the community to find the best patients for the treatment and help them decide whether continued treatment is in the patient's best interest. As for BCVA, it's not a primary endpoint. Most of these NPDR patients have relatively good best corrected visual acuity. And NPDR in and of itself, unless there's quite a bit of macular ischemia involved in it, typically retain good vision. So it's something that we were obviously measuring, but we don't expect significant changes in BCVA in either the treatment or the control arms.
spk10: Thank you. One moment for our next question. Our next question comes from Jennifer Kim with Cantor Fitzgerald. Your line is open.
spk17: Hey, guys. Thanks for taking my question, and Dr. Ribeiro, glad to see another retina guy on the team. Maybe to touch up on the last question, since NPDR is around the corner, what do you think is the most important read-through from the NPDR study to the DME study, given the differences in endpoints and the payload of the inserts and the different duration of therapy? And I guess, ultimately, what kind of profile or other market dynamics are you assuming when you talk about modeling a potential, like, billion-dollar-plus opportunity in DR and DME? Thanks.
spk07: Thanks, Jennifer. So, I think the number one read-through is, up until the PAVEA trial, we hadn't dosed EYP1901 in a diabetic population. And so, obviously, we're looking for some, you know, basic, you know, acknowledgements that in this population that has a VEGF-mediated disease that our inserts work and are safe. And I can just remind everybody that we did release interim safety data as of last November in the PAVEA trial, and we had no virulence or EYP1901-related ocular systemic complications. So the read-through primarily will be, you know, can we show a benefit in this particular disease? DME is an extension of NPDR, just like PDR is an extension. As eyes get more ischemic and presumably VEGF levels and other cytokine levels go up higher, that's when you start to see this type of leakage in new blood vessels. And therefore, I think if we can show in the NPDR population that we are making a biological improvement, I think that we definitely read through the DME. As to the differences in the studies and the insert payloads, shouldn't matter. Insert payloads, you know, again, they release almost identically. They give levels that are consistent with the payload as opposed to, you know, the difference in the actual inserts. So I don't think those particular aspects of the differences between the Verona trial and the Pavia trial will be of any significance at all.
spk09: Thank you. One moment for our next question. Our next question comes from Greg Civenge with Mizzou Health Securities.
spk10: Your line is open.
spk18: Good morning. Thank you for taking my question. I was curious, in light of the data that you presented in WebMD and in the time since, Have you been able to do any perhaps new market research with either clinicians or payers on their reactions? And if you have, what were the findings? And if you haven't done any, maybe you could just provide us a general big picture comment around what the feedback from the retinal specialist community has been. Thank you.
spk07: Thanks, Greg. That's a great question. And while I would say the formal aspects of both market research for both payers and practitioners is ongoing, and since it is ongoing, I really can't comment on how the new data has changed in a quantitative, formal way, what the practitioners and the payers are thinking about EYP1901. I can say again in a rather qualitative way, the initial interactions we have with the payers are quite positive, and the practitioners the same. You know, again, the data from W02 was excellent. We had essentially no change in visual acuity over the six months after our inserts went in compared to the idea of control, and we did it with a really intact safety record in anatomic data that really went along with the visual acuity data. So as the retina community is exposed to not only the initial data set, but the subsequent subset analysis, I think the enthusiasm amongst the potential for this is definitely growing. And in a recent conference, I think when polled of the new agents that are available, the polled retina specialists put EYP1901 as the most exciting. So I think our message and our great data is getting out there, and I think it will continue to be well received in both those communities.
spk10: Thank you. One moment for our next question. Our next question comes from Colleen Cussie with VAIR. Your line is open.
spk16: Great. Thanks. Good morning. Thanks for taking our questions. On the what AMD phase 3 design, maybe this is something that you'll get more feedback on in your FDA meeting, but can you talk about your understanding of the role of the low-dose arm in the pivotal study design? Do you need to be better than the low-dose, or is that just for masking purposes? And if you do have to be better, is that statistically significantly better or just a favorable trend?
spk07: Thanks. Yeah, thanks, Colleen. So, in our interactions with the FDA, the second arm of our drug was viewed as a way to improve the masking in the study. There was never any indication or suggestion that the lower dose had to perform necessarily any different than the higher dose. However, as we've talked about, the second reason we want to use two doses is that there was no dose response in Davia 2. 2 milligrams and 3 milligrams worked essentially equivalently. And therefore, we want the opportunity to test the dose that's around 2 milligrams And another dose that's possibly lower, that would a dose be delivered by a single insert. And we hope to and expect to power the trial enough that the lower dose could show non-inferiority against the afibrocept control group.
spk09: Thank you. One moment for our next question. Our next question comes from Yale Jen with Laidlaw and Company.
spk10: Your line is open.
spk02: Good morning. Thanks for taking the question. Just for the DME, I know it's probably a little bit later to happen. And in terms of 1901, what its role could play any differently in terms of the potential paradigm differences between the DME and with the wet AMD?
spk07: Thanks, Yael. That's a really good question, and it speaks to the differentiation in the two diseases of how they respond to anti-VEGFs. DMV patients do respond to anti-VEGFs, but the anatomic response is often delayed and takes multiple injections to actually see that response. Therefore, a sustained release insert like EYP1901 might not show a response faster than an anti-VEGF, but we would expect and hope that if the population of diabetics responds the same way that the wet AMD population responds, that we can show a similar benefit to other anti-VEGF agents with a significantly reduced treatment burden. That would be the goal.
spk09: Thank you. One moment for our next question. Our next question comes from Yi Chen with H. Lee Wainwright. Your line is open.
spk19: Thank you for taking my question. Could you provide us with your view on gene therapy being developed for YMD, whether they could be a big competitor for six months or nine months, cysteine therapy for YMD, and whether their application could be limited to most severe patients? Thank you.
spk07: Thanks, Yi. So gene therapy is certainly an exciting advance in the retina field. as a replacement for a faulty gene. It's obviously been approved in that indication and really has been an incredible benefit to patients. Using it as a drug delivery also shows promise, especially for chronic diseases. The issues around wet AMD really have to do with, first of all, what appears to be a relatively narrow therapeutic window between efficacy and safety that the gene therapies need to really thread. And secondly, the question about alternatives. You know, gene therapy is presumably going to be more expensive than current therapies or other therapies in development. And therefore, how does one, you know, either an individual retina specialist or payers or society in general justify the use of a more expensive type treatment if it's not clearly superior to what's out there already? So at a high level, I think all retina specialists are excited about the promise of gene therapy. But in way in particular, there's a really tight needle that needs to be threaded.
spk10: Thank you. And I'm showing no further questions at this time. Ladies and gentlemen, thank you for participating in today's conference. This does conclude your program. You may now disconnect. Everyone have a great day.
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