Q2 2025 REGENXBIO Inc Earnings Call
Speaker #3: Welcome, everyone, to the second quarter 2025 REGENXBIO earnings conference call. If you would like to ask a question during this time, simply press star followed by the number one on your telephone keypad.
Speaker #3: If you would like withdraw your question, again, press the star one. Please note, slide referenced during this call are available in the webcast and at the events page of EGENXBIO's website.
Speaker #3: At this time, I'd like to turn the conference over to Patrick Christmas, Chief Legal Officer of EGENXBIO. Please go head.
Speaker #4: Good morning and thank you for joining us today. Earlier this morning, EGENXBIO released financial and operating results for the second quarter ended June 30th, 2025.
Speaker #4: The press release is available on our website at www.regenxbio.com. Today's conference call will include forward-looking statements regarding our financial outlook in addition to regulatory and product development plans.
Speaker #4: These forward-looking statements are subject to risks and uncertainties that may cause actual results to differ from those forecasted. They can be identified by words such as "expect," "plan," "will," "may," "anticipate," "believe," "should," "intend," and other words of similar meaning.
Speaker #4: Any such forward-looking statements are not guarantees of future performance and involve certain risks and uncertainties. These risks are described in the risk factors and the management's discussion and analysis section of EGENXBIO's.
Speaker #4: Annual report on Form 10K for the full year ended December 31st, 2024, and comparable risk factors sections of EGENXBIO's quarterly reports on Form 10Q, which are on file with the Securities and Exchange Commission and available on the SEC's website.
Speaker #4: Any information we provide on this conference call is provided only as of the date of this call, August 7th, 2025, and we undertake no obligation to update any forward-looking statements we may make on this call on account of new information future events or otherwise.
Speaker #4: Please be advised that today's call is being recorded and webcast. In addition, any unaudited or pro forma financial information that may be provided is preliminary, and does not purport to project financial positions or operating results of the company.
Speaker #4: Actual results may differ materially. I'll now turn the call to Curran Simpson, President and CEO of EGENXBIO. Curran?
Speaker #5: Thank you, Patrick. And thank you, everyone, for joining us. I hope you're having a at summer. Today, I'm pleased to be joined by Dr. Stephen Pakola, our Chief Medical Officer, and Mitchell Chan, our ief Financial Officer, to review the exceptional progress being made by the EGENXBIO team as we prepare for our first commercial approval this year and multiple potential near-term product launches.
Speaker #5: Before we begin, I'd ike to acknowledge the Duchene community and the recent events they have faced. We understand these have been incredibly challenging and uncertain times, and express our deepest sympathies to the families experiencing loss.
Speaker #5: These recent events have only reinforced our strong commitment to deliver RGX 202 as a potential best-in-class gene therapy for Duchenne, we believe that RGX 202 has the potential to safely provide strong functional benefit and durability offering hope for better lives.
Speaker #5: With positive and growing interest from the patient community and physicians, I am very pleased to share that we are accelerating our guidance for RGX 202.
Speaker #5: We now expect to complete enrollment in the ongoing pivotal study, this October. Our ability to move this timeline up from end of year further solidifies RGX 202's position as the potential next gene therapy to market for Duchenne.
Speaker #5: The community is clearly in need of additional options. We continue to actively enroll and open new sites in the affinity Duchenne pivotal trial, with plans to roll directly into a confirmatory study to support our accelerated approval.
Speaker #5: Additionally, we are in the unique position of having drug supply in hand for our pivotal and confirmatory trials. We remain on track to report top-line data in early 2026, submit a BLA in mid-2026, and potentially be on the market by 2027 when the vast majority of the DMD population is expected to remain untreated.
Speaker #5: From the beginning of this program, we implemented a differentiated therapeutic approach. We pioneered a proactive immune suppression regimen to drive improved safety outcomes and reduce the potential risk of known liver issues found in other programs.
Speaker #5: Our phase one, two data to date supports that our approach is effective. RGX 202 also has consistent industry-leading purity levels in Duchenne, with over 80% full-capsule content in our product.
Speaker #5: This is important because higher purity leads to less total vector load delivered to patients, and may contribute to the positive safety profile we've en to date.
Speaker #5: We believe our in-house manufacturing capabilities are a highly strategic asset, and gives us a unique ability to serve the large Duchenne market available at launch.
Speaker #5: We are pleased to announce we are initiating commercial manufacturing this fall at our manufacturing innovation center here in Rockville, Maryland. This GMP facility can produce up to 2,500 doses of RGX 202 per year.
Speaker #5: With our strong momentum, and as the only investigational gene therapy enrolling in a phase three study in North America, RGX 202 is well positioned to be next to market and a potential best-in-class gene therapy for Duchenne.
Speaker #5: Let's turn our focus to our retinal disease franchise. In partnership with Avvy, we continue to advance ADDV, RGX 314, also known as Ceravgene lamparvovec or Shuravec, as the potential one-time gene therapy for chronic retinal conditions.
Speaker #5: I'm very pleased that earlier this morning we announced an update to our agreement with Avvy to advance Shuravec into pivotal phase for diabetic retinopathy.
Speaker #5: Based on positive two-year data from the phase two altitude trial, we will initiate a phase two B/3 trial. The cost of the study will be covered by the accompanying milestones, including the $100 million we receive upon the first patient dosed in the phase two B portion of the trial.
Speaker #5: Stephen Mitch will share more about the data and financials shortly, but let me reiterate our excitement about this program, which gives us another pivotal program in chronic eye care with our partner, Avvy.
Speaker #5: Both wet AMD and DR represent large multi-billion dollar commercial opportunities and we believe Shuravec has the potential to preserve vision and prevent disease progression and serve as a meaningful alternative to today's standard of care.
Speaker #5: Last but not least, the FDA accepted our BLA for RGX 121 now known as Clemizagene lamparvovec for the treatment of MPS2 or Hunter syndrome.
Speaker #5: This BLA was accepted under the accelerated approval pathway with a target PDUFA date of November 9th. Pre-BLA activities are progressing well. We have completed the mid-cycle review meeting and our first PLI and BMO inspections with the FDA successfully with no observations.
Speaker #5: These are exciting achievements and a testament to the exceptional quality of our people, process, and science. If approved, RGX 121 will be REGENXBIO's first approved gene therapy.
Speaker #5: Commercial preparations with our partner, Nippon Shinyaku, are progressing well. Product intended for launch has already been produced and we are committed with our partner to inging this potentially transformative treatment to patients in early 2026.
Speaker #5: These accomplishments demonstrate our seamless and focused execution against our strategy to bring potentially transformative gene therapies to patients. We remain excited for and well positioned to deliver on opportunities ahead of us.
Speaker #5: With that, I would like to now turn the call over to Steve for an update on our clinical programs. Steve?
Speaker #6: Thank you, Curran. Today, we're excited to share updates across our multiple pivotal programs. I'll start with our retina franchise, Ceravec, which is being developed in collaboration with Avvy to treat wet AMD and diabetic retinopathy or DR. First, I'll ress Ceravec for DR. Being evaluated in the phase two altitude trial, using in-office superchoroidal delivery.
Speaker #6: I'm pleased to highlight the data supporting our advancement to pivotal stage. The data slides are available in the webcast and on the events page of our website and you can follow along as I discuss.
Speaker #6: As outlined on slide three, DR impacts more than 20 million people globally. And these patients are at increased risk of developing vision-threatening complications. Moving to slide four, a one-time in-office injection of Ceravec has the potential to provide long-lasting improvement to disease severity and reduce the risk of vision-threatening events or DTEs.
Speaker #6: Using one-time in-office superchoroidal delivery is convenient for the working-age population impacted by DR. Also, this route of administration allows targeted delivery into a compartmentalized space to limit exposure to the vitreous and anterior segment.
Speaker #6: Slides five and six show the altitude trial design and baseline characteristics of participants with non-proliferative diabetic retinopathy, or NPDR. Moving to safety data on slide seven.
Speaker #6: Ceravec was well tolerated at all dose levels. Further illustrated on slide eight, we are very pleased to share that at two years in dose level three, with short course prophylactic topical steroids there were zero cases of intraocular inflammation.
Speaker #6: Moving to efficacy on slide nine, starting with the one-year results. As expected, in the untreated control group, patients generally get worse, with 40% experiencing at least a two-step worsening in their diabetic retinopathy severity score (DRSF). In stark contrast, NPDR patients treated with dose levels two and three are generally improving.
Speaker #6: And now on slide 10 for the first time, we share two-year results. Ceravec demonstrated a dose-dependent increased rate of meaningful DRSF improvement with 50% of dose level three patients achieving at least a two-step improvement without need for any supplemental treatment.
Speaker #6: A rate six times that of historical control. Slide 11 further illustrates the durable efficacy seen over time at dose level three altitude years. Importantly, these imaging results are translating into benefit in s of decreased risk of vision-threatening events.
Speaker #6: On slide 12, Ceravec treated NPDR patients at a dose-dependent reduction in DTEs with dose level three achieving at least a 70% reduction in DTEs compared to historical control.
Speaker #6: In summary, on slide 13, a single in-office injection of Ceravec was well tolerated and demonstrated durable long-term efficacy including meaningful DRSF improvement and significant reduction in the risk of vision-threatening events.
Speaker #6: Based on these compelling results, and in agreement with Avvy, we are initiating a global pivotal program. The initial pivotal trial will be a two-part phase two B3 double-mast placebo-controlled superiority trial including two dose arms of Ceravec.
Speaker #6: The primary endpoint will be proportion of patients with at least a two-step improvement on DRSF at one year. This pivotal trial will have two sequential parts.
Speaker #6: The first part will be the dose selection phase that includes dose level three and dose level four arms from altitude to allow interim evaluation of safety and efficacy to then select the dose or doses to carry forward into enrollment of part two of the pivotal protocol.
Speaker #6: Site selection is already in progress and we look forward to sharing more on this program as we progress. In wet AMD, we are evaluating Ceravec via two different delivery forms, subretinal and superchoroidal.
Speaker #6: Within subretinal, we have two ongoing pivotal trials atmosphere and ascent in the US, Europe, and Japan. These trials continue to progress well with enrollment nearing completion.
Speaker #6: Overall, we remain encouraged by the ongoing progress with Ceravec especially the safety profile observed in our superchoroidal programs. This is particularly notable in the setting of short course prophylactic steroid eye drops.
Speaker #6: A significantly shorter regimen than those used in other gene therapy trials. Moving to RGX 202, a potential best-in-class one-time gene therapy for the treatment of Duchenne.
Speaker #6: RGX 202 is the only microdystrophin construct to include the C-terminal domain. Making it the closest to naturally occurring dystrophin. The CT domain has been shown to prolong microdystrophin activity and preserve muscle health by protecting it against contraction-induced damage.
Speaker #6: This preclinical research was recently published in ASGCT's peer-reviewed journal. This construct, combined with the highest purity levels in the field and a proactive immune suppression regimen, is translating into the clinic with better functional outcomes and a favorable safety profile, including in older boys.
Speaker #6: In June, we presented new positive Phase 1, two interim data for 202 at the pivotal dose, showing meaningful functional improvements compared to expected disease trajectory.
Speaker #6: Notably, at 12 months, all patients demonstrated improvement on time function test compared to baseline. With time to stand, 10-meter walk run, and time to climb results exceeding the minimally important difference.
Speaker #6: The majority of patients were eight years and older at dosing and age when functional decline would typically be expected. 202 also continued to be well tolerated with no SAEs or adverse events of special interest.
Speaker #6: Even at our higher dose level, we have seen no thrombocytopenia and no evidence or signs of liver injury in any patient including as assessed by liver function testing.
Speaker #6: To build on what Curran shared earlier, the differentiated therapeutic approach for 202 includes a proactive short course immune suppression regimen that was developed from the outset of this program in collaboration with the patient community and leading Duchenne physicians.
Speaker #6: We pioneered this approach for improved safety outcomes. We're very pleased with how this patient-focused approach, along with our differentiated product, is translating into a favorable safety profile observed to date.
Speaker #6: We expect to complete enrollment of the 30 patients in the affinity Duchenne pivotal trial to support accelerated approval by October of this year. And we will continue to enroll after that for a confirmatory trial.
Speaker #6: Now onto RGX 121. It's such an incredibly exciting time for REGENXBIO and the Hunter syndrome community with the ongoing progress for our RGX 121 BLA.
Speaker #6: 121 represents a potentially transformative one-time treatment for patients with Hunter syndrome. We look forward to and anticipated FDA decision in November. Overall, we're making significant progress across all our late-stage programs.
Speaker #6: I'd like express my sincere gratitude to all the patients, families, clinicians, site staff, and patient advocacy representatives who have supported these trials. With that, I'll turn the call over to Mitch to review our financial guidance.
Speaker #6: Mitch?
Speaker #7: Thank you, Stephen. Good morning, yone. REGENXBIO ended the quarter on June 30th, 2025, with cash, cash equivalent, and marketable securities of $364 million. Compared to $245 million as of December 31st, 2024.
Speaker #7: The increase was primarily driven by the $110 million upfront payment from Nippon Shinyaku in the first quarter 2025 and the $145 million in net proceeds received from the royalty monetization with healthcare royalty partners in the second quarter of 2025.
Speaker #7: And was partially offset by cash used to fund operating activities in the first half of 2025. R&D expenses were $60 million for the quarter ended June 30th, 2025, compared to $49 million for the quarter ended June 30th, 2024.
Speaker #7: The increase was primarily attributed to manufacturing-related expenses and other clinical supply costs and clinical trial expenses for Ceravec and RGX 202 pivotal trials. Turning to the specifics around Ceravec announcement today, Steve went through the very encouraging data we continue to generate in DR and a new phase two three study that both Avvy and REGENXBIO believe will be designed to strengthen the body of evidence for Ceravec in DR and maximize the probability of success in a planned global phase three program.
Speaker #7: Under the terms that the amended agreement, we are effectively being paid in advance half of the $200 million milestone that would have been earned upon dosing of the pivotal trial.
Speaker #7: We will now be paid $100 million upon first patient dose in the phase two B3 trial and receive the next $100 million upon dosing of the first patient in the second phase three trial.
Speaker #7: This brings in $100 million upon first subject dose and more than covered the cost of the phase two B trial. Additionally, the amendment reflects Avvy's continued investment in the Ceravec program and their independent pursuit of the phase three achieved trial to further support the global commercial opportunity.
Speaker #7: We expect the June 30th cash balance reported today to fund our operation into early 2027 and enables us to accelerate towards multiple product launches.
Speaker #7: Please note this cash funding guidance does not include multiple non-dilutive financing opportunities that could further extend our cash runway significantly beyond 2027. These include development or sales milestone for RGX 121, the sale of our anticipated priority review voucher for RGX 121, development milestones associated with Avvy's collaboration including those in diabetic retinopathy program as well as the potential additional funds from the May 2025 healthcare royalty reement.
Speaker #7: With that, I will turn the call back to Curran to provide final thoughts. Thank ou, Mitch. Today's exciting updates make it clear that we are executing at a high level across all aspects of our business, bringing us one step closer to becoming a commercial company.
Speaker #7: Our strategy is clear and focused. With our leading in-house and end capabilities, we are rapidly advancing multiple late-stage programs. These potential first or best-in-class gene therapies represent the opportunity to address significant unmet need for patients with rare and retinal diseases.
Speaker #7: We have our first potential FDA approval on the horizon this year. Most importantly, we maintain a strong financial position and have multiple avenues for non-dilutive financing to support the continued development and potential commercialization of our products.
Speaker #7: I want to thank our REGENXBIO team for their dedication, our physician partners for their collaboration, and the patients and families who participate in our trials.
Speaker #7: Your contributions are essential to our mission of improving lives through the curative potential of gene therapy. With that, thanks for your time today. I'll turn the estion call over for questions.
Speaker #7: Operator?
Speaker #8: Thank you. We will now begin the question and answer session. If you have dialed in and would like to ask a estion, please press star one on your telephone keypad to raise your hand and join in queue.
Speaker #8: If you would like withdraw your question, simply press star one again. If you are called upon to ask a question in our listening by speaker phone on your device, please pick up your handset to ensure that your phone is not on mute when asking your question.
Speaker #8: Again, press star one to join the queue. Our first question comes from Judah Frommer from Morgan Stanley. Please go head.
Speaker #9: Yeah. Hi, guys. Thanks for taking the estions and congrats on all the progress updates here. Maybe one on DMD and then another on DR. I guess with DMD, anything you can share regarding reaction from the DMD community, maybe more specifically about the conditioning or prophylaxis regimen that you have in 202?
Speaker #9: It seems like the community's probably a little more attuned to sirolimus specifically, you know, after that patient death in Brazil. So anything you can share about how the community's feeling about that regimen and then switching to DR, I ess, any thoughts on what's happening in dose level three between year one and year two to see that improvement in DRSF and more generally can you share with us kind of how the discussions with Avvy went in changing the plan for the pivotal design here to go through the two B and then the three?
Speaker #9: Any change in the level of excitement from them, or is it more just kind of proving out the dose level? Thank you.
Speaker #7: Sure. Thanks for the questions. I ink on 202, I would characterize the interest at the patient community as kind of at an all-time high for our type of program.
Speaker #7: I think certainly the proactive immune suppression regimen that we've talking about since the beginning has even greater appeal in this way that people think about safety and high-dose AAV treatments.
Speaker #7: And I ink we are seeing that in our interest in the study itself. And we're doing things like conducting webinars with Cure Duchenne to maybe more broadly get the word out about the program.
Speaker #7: And obviously, as related to enrollment, we're expanding sites pretty dramatically this year. I think, you know, at a base level, the interest in gene therapy is still very strong in the patient community.
Speaker #7: And I think the interest in our program in has risen dramatically. The one thing I would say is I think the patients initially, the immune suppression regimen was portrayed as onerous and potentially not commercially viable.
Speaker #7: We're finding that the patients actually love the level of monitoring and surveillance that we're doing as it related to the study. Because I think it brings them comfort that none of these hopefully none of these events that are controllable will occur.
Speaker #7: I ink I'll ask Steve to characterize the DR data if that's okay?
Speaker #10: Sure. Thanks for the questions. Judah. So, you ow, as you you pointed to the improved efficacy that we've seen over time, how do we look at that data?
Speaker #10: Yeah, think the overarching aspect is you certainly want durability to really confirm that you have the sustained anti-VEGF activity. And I think if you're having disease modification then you even have that opportunity to see continuing improvement even after a single administration.
Speaker #10: And think that's the part that is so compelling particularly for this indication that you can have a single injection that has durable benefit both in terms of DRSF imaging improvement but also very key preventing those vision-threatening complications.
Speaker #10: So I really think that we would have been excited with stability across the two dose levels but to actually see this improvement at dose level three at two years has really given both us and Avvy the excitement to pivot in a positive way to really make sure we 't leave any efficacy on the table.
Speaker #10: You know, it's worth noting this data you know came in first half of this year. So we were rolling along planning to move ahead, given that we'd already met the target product profile.
Speaker #10: But now we've got this amazing opportunity. And it's not only the efficacy side, but it's key that we're seeing excellent safety without intraocular inflammation with a relatively short topical steroid regimen.
Speaker #10: So we have the flexibility to potentially not leave efficacy on the table because of our safety that we've seen with our compartmentalized delivery. So that's really how both we and Avvy are looking at this as a tremendous opportunity.
Speaker #9: Thanks.
Speaker #8: Our next question comes from Gina Wang from Barclays. Please go head.
Speaker #11: Thank you. Maybe I just follow Steve your comments. Is that the reason you wanted to add in dose level four for the pivotal study phase two B?
Speaker #11: To evaluate the potential further improvement with a higher dose and giving a good safety. And also for the pivotal study, are you thinking about one year or would that be two years study?
Speaker #11: Related question is what is the reason to amend the agreement? And if Mitch, you can share with us how much cost will be for the running the phase two B study?
Speaker #11: And then quickly on DMD, just wondering if you have any recent interaction with the FDA since the COVID down departure. So as well Prasad departure, any concerns regarding the pivotal path that was agreed on by the prior administration?
Speaker #7: Thanks, Gina. I'll start and maybe work my way backwards to the questions. I ink on FDA we're certainly having a lot of interaction with FDA as it relates to the Hunter program now.
Speaker #7: I don't think there's a if it's a new facility inspection the PLI that we mentioned that has come in with no observations. We're super proud of that.
Speaker #7: And I think that not only plays well for our chances of approval on 121, but our future chances of approval on the Duchenne program and, of course, 314s.
Speaker #7: So we're really pleased with the FDA interactions that we're having. And we haven't seen any shift more broadly on say clinical trial design, etc.
Speaker #7: to date. On any other programs so I would say right now it's still what we've been saying which is consistent interactions with FDA. As expected in the late-stage reviews that we're encountering.
Speaker #7: The Steve, I'll ask you to maybe comment on the question on actually before I do, I think Mitchell characterized the milestone amendment change but there's actually a mechanical aspect to that that in the original contract a phase two B wasn't really ever contemplated.
Speaker #7: So we were actually pleased to see Avvy basically update that amendment to recognize the two B and initiate part of that full milestone as part of that.
Speaker #7: That was something that I felt helped us in terms of cash runway being able to be paid at the initiation of the two B rather than how it was originally written as first patient in a pivotal.
Speaker #7: Even though we see the two B as being intimately combined as a pivotal. Steve, did you want to comment on the question regarding DR?
Speaker #7: For DL4?
Speaker #10: Yeah. Yeah. Hi, Gina. So the first part of your DR question why DL4 certainly it's both efficacy and safety the fact that we saw the improvement in DL3 and that data coming in at two years in the first half of this year.
Speaker #10: The other piece the equation is safety and as you know we have our altitude DME arm with DL4 as well as our AVA wet AMD dose level four arm.
Speaker #10: So in the first half of this year we got to take advantage of interim follow-up on these patients including those earlier months after dosing which really gives you the read on the key time period as far as safety and tolerability.
Speaker #10: So in short, we're seeing what we want to see in terms of efficacy in the DR study as well as what we see across dose level three and four.
Speaker #10: So we're going up because we can and I think it makes sense that you really don't want to leave efficacy on the table and it's worth evaluating in a dose selection phase when you think of how massive this DR opportunity is.
Speaker #10: Particularly for a one-time in-office treatment we and Avvy felt this was a great opportunity where we can look at two separate doses to really risk mitigate leaving anything on the table and as you know as well it's not uncommon in retina pivotal trials where relatively speaking they're not too large that you can often take two doses into pivotal.
Speaker #10: So we're really trying to keep open our options given the results that we've seen.
Speaker #7: And I ink Mitchell has a comment. Oh, I'm ry. I missed that, Steve, on the one or two year endpoint. Sorry.
Speaker #10: the benefit of a lot of regulatory history with the FDA including our prior end of phase two meeting where we know that this DRSF endpoint is accepted.
Speaker #10: For adequate and well-controlled trials and we know it's accepted at one-year time point. So it makes sense for us to take advantage of that opportunity.
Speaker #10: So the primary endpoint is at one year.
Speaker #7: Sorry for interrupting, Steve. Mitch, did you want to comment again on the milestone structure?
Speaker #8: Yeah. Absolutely. And it's a great estion. I would say the $200 million remains intact. I think as Curran kind of mentioned, the amendment was made because the phase two B was not contemplated earlier so in total the 200 is basically split into two, 100 and 100.
Speaker #8: And the first $100 million will more than cover this clinical trial for the phase two B. We don't want to go into specifics in terms of the cost.
Speaker #8: But I will reiterate that the $100 million will more than cover the study costs. Thanks for your estion.
Speaker #11: Thank you.
Speaker #8: Our next question comes from Manny Parrubar from Lyric Partners. Please go head.
Speaker #12: Hey, guys. You have Ryan on for Manny. Thanks for taking our questioning and congrats on the update. So I know it's early days still enrolling the pivotal but as you guys look to a DMD launch playing out, I'm kind of just curious how you see the dynamics of the broader prevalent patient population versus those ineligible for existing therapies right now.
Speaker #12: Like do you see the first part of launch really being tailored to one more than the other or is this just going to be a pretty broad launch across the board?
Speaker #12: And then maybe just one on wet AMD. Now can you just talk about whether the subretinal launch is a means to the superchoroidal or whether you see a durable albeit smaller market for this type of approach?
Speaker #12: Thanks.
Speaker #7: I can start with the second question. I think we see it subretinal as an entity on its own. Now obviously if down the road a superchoroidal wet AMD approach for Ceravec has the same product profile in the clinic as what we're seeing in subretinal, you could argue that the in-office procedure would be preferable.
Speaker #7: But I think there will always be as well certain geographies that are very amenable to the subretinal administration. We're seeing really robust recruitment, example, in Europe on our subretinal study.
Speaker #7: So I think that both are very viable. And I think the subretinal product profile and clinical data we're eing can sustain itself. So time will tell.
Speaker #7: I think on the approach to the commercial market for Duchenne, if you look our study design, we're recruiting one and older. So we see the opportunity here for a broad label and we see the opportunity with a differentiated product that we're seeing strong functional benefit favorable safety profile.
Speaker #7: We see opportunity to take a dominant position in the market based on our initial data. Right now we're not exploring the non-ambulatory aspect of Duchenne.
Speaker #7: And that's something we're still contemplating although you can make the thesis that our immune suppression regimen would be incredibly favorable for that patient population our focus is 100% on the ambulatory study that we're running now.
Speaker #7: And a broad label is the outcome.
Speaker #12: Awesome. Thanks, guys.
Speaker #8: Our next question comes from L. Mary from UBS. Please go head.
Speaker #13: Hey, guys. Thanks for taking my estion. Just a follow-up on the last question. Just curious how you're thinking a potential strategy in non-ambulatory patients given your preconditioning regimen and curious if you've had any discussions with the FDA on that in the past and any color you can share in terms of how they might be thinking about non-ambulatory safety.
Speaker #13: And then just second, as we think the subretinal phase three which will be a major catalyst when that comes up, can you elaborate a little bit on what you think would be sort of competitive or clinically meaningful particularly as we look towards some of those secondary endpoints?
Speaker #13: Thanks.
Speaker #7: Sure. I think on the question around non-ambulatory, we have not one aspect I would point out for our ambulatory ongoing pivotal study which we pointed to completion in October we do have a broader set of mutations allowed in the inclusion criteria than other studies.
Speaker #7: So we are taking, as I said, a broad approach to the label not just age but also mutation status. I ink in non-ambulatory there's still a lot to learn.
Speaker #7: From some of recent events that we've all heard about. And I think we're taking a cautious approach to that right now. We have not had detailed discussions with the FDA around a non-ambulatory study design but that is something we plan to.
Speaker #7: But I think that's going to be related with expansion of our safety database in our existing program. We want that to be a prerequisite to exploring non-ambulatories that we establish early on a good safety profile in the ambulatory population.
Speaker #7: I'll ask Steve to comment on the subretinal question for secondaries.
Speaker #10: Sure. Hi, Ellie. Yeah. I think as you mentioned it's a very significant milestone coming up the completion of our two pivotal trials for subretinal treatment wet AMD.
Speaker #10: You know, as far as what we're looking for and what we think will fill a significant unmet need in the space, the two aspects are of course the primary endpoint where safety has to be maintained and we need to show non-inferiority on VA both from a regulatory standpoint but also from a commercial standpoint.
Speaker #10: You raise an important point on the secondary. Endpoints particularly the injection burden. Because with a one-time injection that's certainly one of the key value propositions here.
Speaker #10: Where we know that patients are not getting the injections in the real world and are continuing to lose vision. So what how do you quantify that?
Speaker #10: Well, it roughly hasn't changed over time. Where what we hear from clinicians in a lot of discussions that we've had over the years and it's been pretty stable that we'd like to see at least a 50% reduction in injection burden.
Speaker #10: And to be able to achieve that with a one-time injection while maintaining vision in a controlled study where the control arm is getting very prescribed on label treatment, we believe that not only will lead to lower injection burden and treatment burden for patients in the real world but because they have that sustained anti-VEGF activity it also will be a benefit for vision maintenance.
Speaker #10: Which really makes the total package of the value proposition quite compelling.
Speaker #13: Great. Thanks.
Speaker #8: Our next estion comes from Luca. I see from RBC. Please go head.
Speaker #14: Oh, great. Good morning. Thanks for taking our questions. This is Lisa on for Luca. Maybe just on diabetic retinopathy. Just wondering if you can walk us through the potential path to approval here.
Speaker #14: Can the phase two B3 be used as a registrational study alone or will an itional two phase three studies be required for approval? And maybe just on the efficacy here, for DR, you know it looks like 50% of patients did not require further treatment.
Speaker #14: But just wondering if you comment on the 50% that did. Did they go back to a regular cadence of anti-VEGF injections? Or did they need only periodic supplemental injections?
Speaker #14: And just last one on subretinal. For wet AMD on the pivotal study, can you comment on the state of enrollment? Has this trial been fully enrolled?
Speaker #14: And if so, when did enrollment close? And that's all for me. Thanks so much.
Speaker #7: Thanks for the questions. I can start with the last one around subretinal enrollment. We're seeing really robust enrollment and I think we're in a situation where completion of enrollment is essentially imminent.
Speaker #7: But we will certainly update when those studies are both fully enrolled looking forward to that. But we feel really good about enrollment. And as I mentioned earlier, maybe unexpectedly really strong trend in enrollment in Europe which Avvy is conducting those sites so stay tuned.
Speaker #7: And that's why we continue to guide to top-line data in 2026 based on optimism around completing enrollment for those studies. I'll ask Steve to comment on the DR data.
Speaker #10: Yeah. So the first part of your question Lisa, on the potential path, to regulatory approval, so we believe there is the requirement traditionally needed of course of two adequate and well-controlled studies.
Speaker #10: So that's our plan. Notably, the phase two B3 study that will be starting would be intended to be one of those two studies. So I think that's encouraging.
Speaker #10: That's why we say we're starting our pivotal program. In s of the data from the two-year results that we showed on DL3, 50% of the patients had at least two-step improvement without needing supplemental injections.
At that point would be helpful and then you know, I appreciate the the differences between 2 and 2 and 11 this um as well as the the emerging safety profile for 202. But do you expect um, you know, a class effect for liver injury? Could could be applied to the label, given they are both Ave Gene therapies. Um, and then lastly on, uh,
Uh, on 31 uh 314. I guess, how should we view? Um, you know, the the 2 pivot studies versus the phase 3 achieve study that Abby is planning to launch. Do you think data from the first 2 Sub? Retinol studies will will be sufficient to file with achieve more for um, uh, being leveraged for, for commercialization, um, with with with Physicians. Um, and any color. That would be helpful. Thank you.
Sure. Thanks for the question. Now, uh, the, uh,
Last 1 is is fairly straightforward. The subretinal pivotal studies atmosphere and is sent uh, will be sufficient for uh, filing an approval. Um, and the study that we mentioned today, uh, is really a post marketing approach to judge the advocacy of the product in a against Real World outcomes, so they're very separate. Um, and the 2 pivot that we're running which are highly powered. Um, as a result of some sample size increases we made, uh, we feel will be very adequate uh, for filing.
Um, and I think in terms of the market Dynamic at launch, uh for uh back to your question on 202.
We certainly see a really significant level of the prevalent population still being available to us.
Based on some of the interruptions, uh, in launch, uh, maybe greater than 90% of, what we initially, uh, estimated of the prevalent population. So, uh, that that will lead us to potentially, um, at launch itself
I think um where we're positioned uh in terms of timeline and uh our differentiated product profile uh really makes this uh potential Blockbuster opportunity.
Uh, on the question around uh delaying on the member injury. Yes. Can you guys? I was gonna defer that to you question? Yeah.
Okay. Uh great. So Alec uh, yeah, you refer to uh, the existing therapy.
And the uh liver uh, injury components and liver failure components in the label.
And how that could.
Potentially lead to any kind of class.
Uh, affect considerations. I, I think each program has to be looked at in its own, right. And I think that's why the points current has made about the clear differentiation that we have. In terms of product Purity with a much higher full to empty capsid, uh, ratio that's industry-leading. And, of course, our proactive immune, uh, modulation approach,
And the existing therapy, uh, has uh, per label.
Up to 40% rate of liver injury.
And I think we're seeing, uh,
Are differentiated approach.
Translate in the clinic to a clear differentiation in terms of risk of liver injury where we in our Phase 1, 2 studies. See 0 of 13 patients with any signs or symptoms of liver injury including on lft assessment. So,
this gives us a lot of confidence in terms of how we can show differentiation on safety overall, uh but also in terms of potential risks to deliver
Our next question comes from Jack. A devano from stifel, please go ahead.
Hi team. This is Jack on for Annabelle, thanks for taking our questions. Um, so on the rationale for the phase 2B with 314. I, I know you mentioned that you don't want to leave efficacy on the table, which makes sense. Um, so the 2-Step Improvement for dose level, um to seemed equivalent to um, dose level 1 at year 1. Um,
Or sorry. I think I may have gotten that mixed up for dose level 3 equivalent to dose level 2 year 1. Um and the real differentiation only emerges at year 2. What was the decision to include dose? Level 4 here, partially driven because you feel like you need to improve efficacy even further to sufficiently convinced FDA with just the year 1 data, kind of, essentially asking if that 2122 percent efficacy is sufficient for approval already and you just think you can do even better.
I think it's the latter, I think we feel those level 4 has the opportunity to do better, but on its own uh the dose level 3 results. We feel are sort of the anchor dose that met our product, uh, profile. Um and would be I think received well uh in a review, Steve, do you want to come in a little bit? I'm just the, the power of the the signal that we're seeing.
Sure. So Jackie you you point to the equivalents in terms of 2 Step Improvement at 1 year.
The key consideration is the effect size. We're seeing their meets our Target product profile and the reason it meets that is is we know that that's an acceptable endpoint and a acceptable effect size from a benefit risk standpoint. When you take into account, this being a single injection and the ability to decrease treatment burden. When you look at that, overall benefit risk consideration, the other key aspect is what the clinicians care most about is.
Held up to a very significant uh clinically uh meaningful level at the 2 year time point. So that's why we and Abby uh you know feel very comfortable with the 1 year endpoint and we know we're going to continue to get to your data and long-term data to give even more confidence to the clinical community.
Great, thanks.
Our next question comes from Brian's Courtney from bear. Please go ahead.
Hey, good morning everyone. Thank you for taking my question. Um, also want to just uh um push to get a little more granularity on the Dr. 2B versus your 2B 3 versus 3 study design. On the 2B is this is this a 2B portion where you get some interim data from a small sample size and then roll into a phase 3 portion or is, is sort of a whole thing running blinded before full readout. I'm trying to get a feel for the Cadence, um, where this is going to be 1, read out. And then you would start the second pivotal phase 3 or there's an earlier. 2B portion read out that leads to a start of the phase 3 portion of the 2B 3. And then at some time later at the start of the second phase 3 portion and in terms of the control arm is it going to be sham or open label and, and have you potentially thought about an active control in any of these studies just looking at the event rates, uh, you have in Deal 3. Um, it would be out of the questions even potentially show benefit of, or
overly a particularly um if events are compliance driven though,
Thanks for the question, Brian. Um, I think uh, at a high level, I can comment the the way the 2B is designed is to efficiently as efficiently as possible move through different phases. So it's structured that the 2B has
An interim readout in which it rolls into a phase 3 and the concept. Uh, and uh, the, you know, the plan with uh, Abby is that would also trigger immediately, uh, starting the second pivotal so that we could go as quickly as possible. Uh, let's Steve comment on the other details. You asked about
yes, I think, uh,
That the key is really that the the phase 2B 3 study.
Uh we are going to roll over into uh the part 2 of that study and it's all under 1 protocol.
so, uh,
Yes, the the part 1 informs that. Now we we do plan to take advantage of interim. Looks at that data to really help informed by assessing ongoing safety and efficacy of the ability to then Advance into part 2.
On your your second uh question. Uh both pivotal including uh part. Uh 1 of the first study will be double masked so we really want to get the highest quality from these studies. So we are going to use a sham injection uh to get the the greatest validity in terms of looking at actual treatment effect.
the, the interesting question about ActiveX control for diabetic retinopathy before,
uh, Vision threatening events has occurred is that while other drugs like Isaiah,
Have uh, treatment of Dr. On label. The reality is, this is clearly not standard of care precisely because of the unsustainable treatment. Burden of repeated, injections indefinitely because when you stop those repeated injections patients rebirth and you you wind up, going back to the risk of vision threatening events. So even if we wanted to run a active compare comparator, it would
Frankly, bank enrollment is almost, uh, impossible because patients don't want to go through that repeated injection. So it basically validates why we feel a one-time injection has so much potential for this massive unmet need.
And and the inclusion Steve of the Sham control was something we covered in. All of the regulatory sessions we had last year, is that correct?
Yeah, that's right. That's always been our plan and uh, we've always had alignment with the FDA on that.
Thank you.
Our next question comes from Bill.
Logan from Clear Street, please go ahead.
Hi, good morning and thanks. So you've mentioned a few different aspects of 202 that make it differentiated from 11. As those being, for example, the full capture ratio, uh, your manufacturing process and your immune modulation, uh, condition and regimen. So I I just wanted to ask around the the immune modulation. Um and whether or not you think that that is the majority of the differentiation. And if so if you simply added immune modulation to 11, this is there a chance that this could become more similar than different in terms of safety. Thank you.
Thanks for the question. Um, I think in general, it's hard to to pull those apart from each other. You know, we wouldn't have preclinical data where we look at each effect, uh, in isolation, but maybe I'll let Steve's comment. I, I do believe, uh, from what we're seeing, um, that they all play into effect because our goal is to deliver. The maximum dose that's in line with our pre-clinical data to deliver a functional benefit, and that's what drove us really to initially. Go to the highest Purity we could, which is above 80%. Um, but the immune suppression was a separate. Um, uh,
Separate thoughts from our clinical Development Group. As Steve mentioned.
Put together. I think that both of them have power in establishing the safety profile that we've seen so far. But I can't comment on whether or not uh that'll mean suppression regimen would perform the same with elevators Steve. Do you have thoughts on that?
Yeah, I I agree that uh we we think all all of these components play a part. It's really not.
Possible to give any, you know, percentage, uh, breakdown on on that and they probably all interact as well. I, I think 1 of the key considerations is
because we built this in upfront because we cared about safety in uh the overall sense of benefit risk for our product and and realize that that was a key differentiator
We're the only program that actually has safety.
And efficacy data, where we can.
begin to answer that question in terms of,
With this constellation of differentiation, are we seeing a favorable safety profile? So,
uh, as Karen mentioned, we don't know what would happen with other programs if they added any of our proactive immune modulation. So, that, that would remain to be seen
Thank you.
Our next question comes from Sean, from Raymond James, please go ahead.
Hey guys, thanks for squeezing. Me in 1 on uh on 202. So you know, moving the, the full enrollment of that pivotal Co cohort uh, up to October. Can you speak to the the flexibility? This may allow you to potentially over enroll, um, or to get a head start on the enrollment of the confirmatory, study, to position yourselves. Well, amidst, some of the shifting, let's call them perspectives and uncertainty at the FDA. Thanks.
Thanks. That's, that's a great question. Uh, I think we've pointed out in the release and and other venues that we do it intend to continue to enroll, uh, once we fully enroll the pivotal program. Um, our protocol was originally written uh, to, uh, uh, enroll approximately 30 patients in the pivotal arm.
And then an additional 30 patients in the, uh, confirmatory study as well. So we have, uh, plenty of room to continue to add patients throughout the year, and we can make amendments along the way, but I think, uh, I would express our main goal is to continue enrollment and expand our safety database. We have, uh, all of the drug Supply we need, and we're making more as we pointed out, um, because we think that that will be important, and it will address any risk in sample size discussions, for example, um, and, uh, that's, uh, 1 of the rationale as well is why we're expanding sites dramatically from where we were only a year ago.
Next question comes from Daniel godlin from chardan. Please go ahead.
Hey, good morning. Uh, thank you for taking my question. I have a couple, uh, first on 202. Um, given the uncertainty in the, uh, DMD gene therapy space. Um, I considering requesting another meeting, um, with the FDA, uh, before your previous has not changed to dramatically, uh, maybe if, uh, you can mention if you can, if you're considering a special protocol assessment for to
Um, and second for 314, uh, with your super CoroSpace micro in. Check your partner. I'm going through a significant restructuring. Uh, what is the strategy to ensure that you have access to micro injectors going forward? Um, and are you considering switching to a different micro injector partner? Thank you.
Sure, I can address the excuse me, the last question first. Um I think uh we feel confident with uh continued supply of micro injector, regardless of uh business situation uh with uh clear side. Uh we have uh significant inventories in hand and also Provisions for continuing Supply. That were part of the original.
Uh, uh, contract that we've signed. So we feel very confident, um, in our ability to continue to access the devices and are in close contact uh, with clear side as well to just ensure no no issues with continuity.
Um, in terms of the
just trying to pull back to the first question, uh, an FDA meeting sooner than planned. Uh, that's something I think we're thinking about, um, I don't think there's any urgency to do that because right now, our primary, uh, goal is enrollment, and not just the pivotal, but the confirmatory study. Um, and as we get further along, uh, I would expect, we'll look for a check-in, uh, with FDA. But I don't think right now, we're getting any signals from FDA, uh, that make that urgent because we're in constant contact with the review teams, both for 121, and for 202. We're not detecting any significant shifts in, uh, in uh, what they're looking for in the study or, uh, study design. And I think in particular, uh, mccary's statements about rare disease development, I think the, uh, situation in duchan
Over the last couple of months, this is only underscored the need for additional therapies to be available. And for that to be done urgently and I feel like our data package. If what we did in Phase 1 2, replicates in our pivotal program will be very compelling for FDA.
Our next question comes from Paul Choi of gold. Mine Sachs, please go ahead.
Hi, uh, good morning, and congratulations on all the progress. Um, thanks for taking our questions. I want to maybe, um, you know, continue, uh, the questions just on the FDA landscape here, and, um,
I guess, you know what, your confidence for the DMD program is in the absence of a permanent head of severe, uh, just giving the uh, the, uh, sort of focus on, on that particular disease, State and indication. Um, then my second question is, um,
I guess uh, as you think about, uh, the Medicare changes to the uh uh and recent ra changes for uh, reimbursement of injectable veg apps. Uh, you know, how are you? You know, potentially thinking about pricing um, for for your product there, uh, over the longer term given, what seems to be continual downward pressure from from the Medicare reimbursement side. Thank you very much for taking our questions.
Uh, if you think about it, uh, we are enrolling, our pivotal study. We've said that we will conclude that in October and then we will continue uh, enrollment for the confirmatory study. Uh, we will probably still be enrolling. The confirmatory study at the time of our previous meeting. And so if there's anything that surfaces, uh, along the way, we have the opportunity to adjust and either increase, enrollment, if that's the asked, uh, or, uh, stand on our data, which we think will be extremely strong. Um, and so, I don't think there's any near-term need to, uh, contact leadership at FDA. We have good contact at the review division level and avenues for information requests and going back and forth or meetings type-c meetings. If we choose uh, these out other elements of it. But I do want to reiterate our pivotal Proto.
Call was reviewed by uh the review team um that was very similar to the team that reviewed 11th. Um, and in detail,
And that review team from what we can tell is largely intact today. Even though there have been many changes in leadership FDA. And I think that's that's, uh, comforting to us. And, uh, again, the urgency for additional Therapies in duchin, couldn't be at a higher level. In my view, based on what we've seen happen, over the last couple of months
Our next question comes from Ken from the Rain, right East. Go ahead.
Thank you for taking my question. Uh, could you please uh comment on whether the the zoom level of survey back for the subretinal delivery for William B is much lower than the super Cordo delivery, uh, for Web MD, ER and vme
And whether the dozing difference is associated with the route of delivery to achieve uh, similar ethics, thank you.
Thanks. Uh, Steve. I'll have you comment on that.
Sure, thanks for the question you. So, uh, the
Doses that we're looking at in the subretinal pivotal studies are lower. Uh, these are 2 separate routes of administration. We we've been leaders in the exploration in uh super Carro.
Uh, looking in across 2 different indications. So, we knew from the start that different routed Administration and also in the case of diabetic, retinopathy different indication with different vegf drive that we had to really look for a dose response, a new in that new route of administration. Uh, and so we thoroughly looked at that and also looked at safety with this new routed Administration where uh, going higher on dose, we knew we had that flexibility.
Uh, from our pre-clinical data so here as well. We um were able to go higher and
So importantly, uh, not only the the clear meeting of Target product profile with the super Frey.
But also, uh, we wanted to replicate the good parts of subretinal.
but not needing a, um,
a surgical procedure, so to be able to do that in office and
Early on, we chose Super Croyle because it preserved the targeted local delivery into the.
Uh, a compartmentalized space, the super croyle space and that really increases the the belief in in safety both within the eye or any systemic effect. Uh, so we, we also have bilateral dosing, uh, with good safety, uh, and efficacy results that we've seen in a bilateral study. So all these, this constellation of aspects had us,
Confident to be able to go higher on dose uh with this new route of administration.
There. No further questions at this time.
And this concludes today's conference call, thank you for joining. We may now disconnect