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spk14: Good afternoon. My name is Sarah, and I will be your conference operator today. At this time, I would like to welcome everyone to the Appellate Pharmaceuticals first quarter 2021 financial results conference call. Today's call is being recorded, and a replay will be available at appellates.com. I would now like to turn the call over to Tracy Benise, Vice President of Communications at Appellate.
spk01: Good afternoon, and thank you for joining us to discuss Appellus' first quarter 2021 financial results. With me on the call are co-founder and chief executive officer, Dr. Cedric Francois, chief medical officer, Dr. Federico Grossi, chief commercial officer, Adam Townsend, and chief financial officer, Timothy Sullivan. Before we begin, I would like to point out that we will be making forward-looking statements that are based on our current expectations and beliefs. These statements are subject to certain risks and uncertainties, and our actual results may differ materially. I encourage you to consult the risk factors discussed in our SEC filings for additional detail. Now, I'm pleased to turn the call over to Cedric.
spk02: Thank you, Tracy, and good afternoon to everyone joining us today for our conference call. It is an exciting time at APELIS with the potential U.S. approval of texetacoplan and paroxysmal nocturnal hemoglobinuria, or PNH, just a couple of weeks away. We are fully prepared for our PDUFA date of May 14th and ready to launch Bexita Co-Plan shortly after approval. Our Chief Commercial Officer, Adam Townsend, will provide the latest updates on our efforts to ensure a successful launch in P&H. As this slide shows, we are focused on advancing our global leadership in continent, and our potential approval in P&H is just the start to what will be a transformational year for Apedis. With PNH as our lead indication, we aim to establish systemic texetacotin, our targeted C3 therapy, as a disruptive treatment across rare complement-driven diseases. We plan to become number one in the retina with the first treatment for geographic atrophy, and we continue to advance innovative technologies to control complement with a focus on complement factor C3. Last month, we were thrilled to see results from our programs in PNH and Geographic Atrophy, or GA, published in three leading medical journals. In PNH, results from our Phase III Pegasus study were published in the prestigious New England Journal of Medicine. The recognition by NEJM underscores the importance of the Pegasus data to the PNH community and the high caliber of science that we are advancing at Abelis. Additionally, Two separate analyses of our Philly study in GA were published in the American Journal of Ophthalmology and Ophthalmology. Our chief medical officer, Dr. Federico Grossi, will provide additional details later, but together, these publications showcase the broad platform potential of our targeted C3 therapy for complement-driven diseases. The GA publications also reinforce our confidence in our upcoming phase three readouts, which we continue to expect in the third quarter of this year. Top line results from our Derby and Oaks studies will be an important event for Abilis and for the more than 5 million people worldwide living with this relentless and disabling disease. Geographic atrophy is a leading cause of blindness and the most significant remaining unmet need in the retina. We believe that targeting C3 has the potential to control the excessive complement activation responsible for the growth of GA lesions, and all of us at Apedis are committed to advancing the first potential treatment for people living with GA. Finally, our world-class researchers continue to develop new technologies to control complement. On June 30th, we will host an R&D day, that will include the new product candidates that we plan to advance into clinical development by the end of next year. These programs are focused on three key areas. Less frequent dosing while maintaining the strong clinical benefit seen in multiple studies of Pexetacoplan. Secondly, treating all forms of AMD. And thirdly, exploring new indications in neurology. We look forward to sharing more details as we get closer to the event. As I mentioned earlier, 2021 is a transformational year for Aperis. We have spent the past decade building the foundation for our leadership in complement, and we look forward to seeing the results of those efforts come together over the next several months. And now I'd like to turn the call over to our Chief Medical Officer, Dr. Federico Grossi, for a review of our pipeline updates. beginning with our work to establish systemic pexetacoplan as a disruptive therapy across rare, confidence-driven diseases. Philippe?
spk18: Thank you, Cedric. I will first begin with PNH, the program that serves as the foundation of our disease franchise. We're all looking forward to our PADUFA date and remain on track for May 14th. The positive phase III PEGASUS results demonstrated the potential of Plexotocoplan to elevate the standard of care in PNH. And the recent publication by the New England Journal of Medicine reinforced the significance of these results for the medical community and patients with PNH. We hope to build on the strong clinical profile of Plexotocoplan soon to date with the upcoming results from the PRINCE study. As shown on this slide, our phase 3 PRIN study in treatment-naive PNH patients is designed to evaluate two primary endpoints at weeks 26. Hemoglobin stabilization in diastasis on transfusions and reduction in LDH levels. These co-primary endpoints were intentionally aligned with those used in previous PNH studies of C5 inhibitors and therefore focused on intravascular hemolysis. However, since PNH is characterized by both intra- and extravascular hemolysis, we believe that certain secondary endpoints, including hemoglobin levels, transfusions, and facet tratex score, are critical measures of the overall impact this disease has on patients. I would also like to remind you that we set a high bar for texetocoplan on the primary endpoint of hemoglobin stabilization, compared to previous studies of C5 inhibitors. In PRINCE, patients are considered to have unstable hemoglobin levels if those levels drop by only one gram per deciliter, whereas studies of C5 inhibitors historically allowed hemoglobin levels to drop by two grams per deciliter before being considered unstable. We're excited to see the results from PRINCE at the end of May or the beginning of June. I will now hand the call over to our Chief Commercial Officer, Adam Townsend, to provide an update on our P&H loan preparations. Adam?
spk03: Thank you, Fede. Our commercial organization is excited and ready for our May-Purdue-for-date, and we are laser-focused on ensuring a successful U.S. launch of PEGcetacoplin in P&H. Our market research continues to reinforce the urgent need for new treatments for P&H. As you can see on this slide, people with PNH continue to suffer from significant unmet needs despite their current treatment with C5 inhibitors like Solaris and Altamiris. Retrospective studies show that one-third of patients on C5 inhibitors continue to require transfusions to address their falling hemoglobin levels. Another third of these patients remain anemic and experience other symptoms like severe fatigue. The final third of patients on C5 inhibitors have closer to normal hemoglobin levels, but many only achieve that at the expense of maximum output of red blood cells from their bone marrow. Thus, we believe there is a significant need for pegcetacoplin to elevate the standard of care in PNH. And our commercial team is ready to address the needs of people living with PNH at launch. Our latest launch preparedness activities are outlined on this slide. Our value and access team is engaging with high priority payers, representing more than 80% of all US PNH patients. This includes completing more than 50 unique payer interactions, during which we received positive feedback on the clinical efficacy and safety profile of Pegcetacoplin. On average, we anticipate that reimbursement decisions to be made approximately three to six months post-launch. We will work hard to make sure that any patient who chooses Pegcetacoplin will have access to it from day one of our launch. We have established our distribution model as well as our patient support resources and programs. This includes Appellus Assist, a program designed to provide a comprehensive support system for patients throughout their treatment journey, including dedicated Appellus care educators who will help train patients on self-administering pegcetocopin. Appellus Assist will help ensure a high-quality treatment experience and provide infusion training continuing education on the treatment of PNH, and ongoing support with copay assistance, where eligibility criteria are met. As we continue to navigate through COVID-19, our team, both commercial and medical affairs, is closely monitoring regional COVID-19 restrictions. In areas where we can have in-person engagements, we have field teams meeting healthcare professionals, or HCPs, in their offices, and we will obviously remain diligent in following all appropriate guidelines. In the meantime, our commercial strategy remains focused on digital education and virtual engagements for both patients and HCPs. We have built a very strong sales force with significant rare disease and hematology experience, and we believe our team has the right skillset to address any HCP access challenges in this COVID-19 environment. Finally, our focused and experienced sales teams are trained, and as of March 1st, have been deployed to cover the top 1,000 to 2,000 HCPs, including more than 90 key treatment centers. We have spent the last two years listening to and engaging with the P&H community in preparation for our launch. Our team has developed a very thoughtful and strategic approach to our launch, reaching first the patients with the highest unmet need, and then transitioning to a broader group of patients. We await the decision from the FDA and are ready to elevate the standard of care with Pegceta-Coplin upon approval. In parallel to PNH, our commercial organization continues to plan for future potential approvals, and we are excited to see the results of our GA studies later this year. I will now turn the call back to our Chief Medical Officer, Dr. Federico Grossi, to review the additional systemic program indications as well as GA. Fede?
spk18: Thank you, Adam. Beyond PNH, we are advancing four registrational programs of systemic pexetocoplan with our partner SOPS. Our disease programs are focused on complement-driven diseases where patients have few or no treatment options. and where we believe targeting C3 has the potential to offer a differentiated product profile. Key upcoming milestones are outlined on this slide, including several study initiations in the second half of this year. In parallel to our work in rare diseases, we continue to execute on our Phase III studies of intravitreal pexetocoplin in GA with top-line results expected in the third quarter. We're excited about the potential of pexetocoplan to become the first treatment for people with GA. And recent publications in two leading ophthalmology journals reinforce the clinical profile of our targeted C3 therapy. Last month, publications in the American Journal of Ophthalmology, or AGO, and Ophthalmology highlighted post hoc analysis of our positive phase two field study of pexetocoplan in GA. The AJL publication showed that pexetafocan reduced lesion growth similarly across patient subgroups, and the results remained significant even when accounting for risk factors associated with more rapid progression. In the ophthalmology publication, the authors characterized the exudations reported in Philly and found that investigators determined exudations were responsive to standard anti-BGF therapy and did not have a clinical meaningful impact on vision. The analysis also found that the exudations were more common in patients with a history of wet MD in the fellow eye. This observation is consistent with real-world clinical data mined from the AO IRIS registry in our ongoing collaboration with Verana Health. Earlier this month, We also announced that 10 abstracts, including five oral presentations from our artificial intelligence collaboration with the Medical University of Vienna's Optima Group, were accepted for presentation at the Association for Research in Vision and Ophthalmology, or ARBO, virtual annual meeting in May. Our strong presence at this important ophthalmology meeting further showcases our leadership position in GA. Also in GA, we recently shared encouraging new 24-month data from our Phase 1b study of pexetacopian in patients with advanced GA and low vision. The study, which enrolled patients with bilateral GA, is designed to assess the safety of the Phase 3 formulation of pexetacopian. Post hoc analysis on eight patients from whom data were available at 24 months demonstrated a 46% decrease in mean GA lesion growth compared to the opposite untreated eye. Of the 12 enrolled patients, there were no reported cases of inflammation, and two patients developed new onset exudation during the 24-month study. Patients were treated with anti-BGF therapy in combination with texetacoplin and experienced no clinical impact on vision. While this is a small study, these long-term results further highlight the potential of pexetocoplin in this disease. Together, these results and publications continue to strengthen our belief in our GA program ahead of our pivotal Phase III GA readouts. As shown on this slide, DERVIA-NOGS are multicenter randomized control studies that compare the efficacy and safety of monthly and every other month intravitreal Plexotocoplan with sham treatment in more than 1,200 GA patients. The primary endpoint of those studies is the reduction in growth of GA lesion at months 12. Full study designs can be seen on these slides. We are excited to see the top-line results from Derby and Oaks in the third quarter. Success here will position us as the leader in the treatment of retinal diseases. I will now turn the call over to our Chief Financial Officer, Tim Sullivan, for a review of the financial results. Tim?
spk04: Thank you, Fede. Since we issued a press release earlier today with our full financial results, I will just focus on the highlights for the first quarter of 2021. As of March 31st, 2021, Appellus had $723.7 million in cash, cash equivalents, and short-term marketable securities. Research and development expenses were $84 million for the first quarter of 2021, compared to $69.3 million for the same period in 2020. The increase in R&D expense was primarily attributable to costs associated with ongoing and planned clinical trials, compensation and related personnel costs primarily due to the hiring of additional personnel, among others. General and administrative expenses were $40.6 million for the first quarter of 2021, compared to $29.5 million for the same period in 2020. The increase in general and administrative expenses was primarily attributable to employee-related costs, professional and consulting fees, and general commercial preparation activities, among others. For the first quarter ended March 31st, 2021, Appellus reported a net loss of $183.7 million compared to a net loss of $168.8 million for the same period in 2020. We remain well capitalized to execute on the potential launch of Pegceta-Coplin and PNH and continue to advance our robust clinical development plan. Our cash runway is expected to fund operations into the second half of 2022. I will now turn the call back over to Cedric for closing remarks.
spk02: Thank you, Tim. We've made strong progress this quarter and have several important commercial, clinical, and regulatory milestones anticipated over the next several months, as shown on this slide. With our PDUFA date for PNH just over two weeks away, we would like to take this opportunity to recognize and thank the patients, investigators, caregivers, partners, employees, and investors who have helped us get to this pivotal moment. We look forward to keeping you updated on our progress. And now, operator, please open the call for questions.
spk14: Thank you. To ask a question, you will need to press star then 1 on your telephone. To withdraw your question, please press the pound key. Again, that is star then 1 if you would like to ask a question. Our first question comes from the line of Anupam Rama with JP Morgan. Your line is now open.
spk06: Question. I was wondering if I could ask a question that I've been getting a lot recently, which is related to the phase three geographic atrophy studies and how you're thinking about presenting some of the top line data as it relates to exudates, whether it's the rate of exudation in the different arms or the portion of patients getting a VEGF treatment or the rate of CNV and how we should be thinking about this. And what are the most important metrics on this topic related from your market research from physicians?
spk02: Thank you so much, Anup. I mean, great hearing your voice. So that is indeed a question that we get quite often. I think the first element to mention there is that we will report these exudations as physician-reported exudations. So in that sense, very similar to how it was done in the Phase II clinical trial, with the caveat, as we have discussed many times before, that the Phase III clinical trial is, you know, better controlled to compensate for potential investigator bias, et cetera. And with the knowledge that in the Phase III clinical trial, the number of patients that came into the Derby and Oakes studies demographically were much less represented by patients who started off the study with wet AMD in one eye already at baseline and GA in the contralateral eye. Because when we did the Philly study, the phase two study, we were competing with another large phase three program that was excluding that particular type of patients. And that matters because it is well known that patients with wet AMD in one eye and the contralateral eye have quite a high rate of exudation development, wet AMD development in the GAI based on a large study that we did to the extent of approximately 21% over the course of two years. I will also briefly hand it to Adam to give a brief feedback on what we have heard from physicians in terms of adoption.
spk03: Thanks, Cedric, and thanks, Ann and Pam. In our market research with GA physicians, be they injecting ophthalmologists or retina specialists, we find that some of the important impacts that resonate very well with them starts with the ability to slow lesion growth. That's the number one piece that resonates very strongly. And then if you use the parameters that we saw within our Philly study, we found that, you know, a clinically meaningful average based on our market research of of less lesion growth is about 20% to 30%. And we get that consistently through KOLs, retina specialists, and ophthalmologists. So lesion size, lesion growth, and the ability to replicate some of the FIDI data very strongly with our prescriber base. They also are very thoughtful around safety, dosing, roof administration, and mechanism. one thing that is consistent is there's an emotional burden for these physicians who currently can't help these patients as much as they can. So we're excited to see the data towards the end of the year, and we hope to really, really have a big impact on GA patients moving forward.
spk06: And then if I could just squeeze one more quick question in. From a high level, maybe you could give us some perspective on your regulatory interactions here going into the PNH program approval in terms of, I guess, you know, I guess there's a concern right now on PDUFA's getting pushed out given kind of the... Yeah, thank you so much.
spk02: And, of course, Anupam, we get a lot of questions on that as well. We are within two weeks of our PDUFA date, so we are not commenting on regulatory questions at this point in time. It is public knowledge that, you know, we went through the whole process without any major findings, and we are hopeful that the middle of this month we'll have something good to tune out. Thanks so much for taking the questions, guys. Thank you.
spk14: Thank you. Our next question comes from the line of Jonathan Miller with Evercore ISI. Your line is now open.
spk09: Hi, guys. Thanks so much for taking the question. Two, one on P&H launch and then a follow-up on GA, I guess. How are reimbursement discussions going for P&H launch at this point? You mentioned three to six months for commercial payers getting through the reimbursement process. Can you talk us through how you expect that payer ramp-up to happen and what percentage of those patients that you're talking about are commercial versus government, and what's the launch-up for government payers as well?
spk02: All right, I'm going to hand that one over to Mr. Thompson. Adam?
spk03: Yep, thank you. Thank you, Jonathan, for the question. So, firstly, our value and access team is fully staffed and has been engaging with the high-priority payers for the last couple of months, and those payers are representing more than 80% of all US P&H lives. One thing that stands out from our payer interactions is they've been hugely positive. We expect broad coverage. and we don't see any major issues with reimbursement. It does take, on average, between three and six months post-launch for us to work with those payers and get through their internal processes. And a quick sidestep to the second part of your question, 50% of the patients that we expect will have commercial private insurance, and the other 50% are governed under Medicare insurance. and Medicaid with some slight error bars around the edges. We expect that on the Medicare plans, they typically take up to about 180 days, and the Medicaid plans up to about six months. And as I said before, the commercial plans three to six months. Our team is really, really impressive in how they've been interacting with the payers. The value story of PECS set to Copeland is very, very strong. So we believe that we'll be able to smoothly move through those discussions with the U.S.-based payers, and we're prioritizing access. So any patient that wants to come onto our drug will be given access, even as we work through that payer landscape, as I've described.
spk09: Great. That makes sense. And I guess then a follow-up on GA. I noticed that you highlighted some of that efficacy update you gave from the Phase I Safety Study. but it looks to me like the efficacy delta we're seeing there has plateaued a little bit versus the last update. Obviously, still very impressive headline number, but should we expect this to be the general observation with Teixida-Copeland and GA? Should we expect there to be this plateau at around that 50% level, or could that delta continue to expand as dosing continues?
spk02: Yeah, thank you so much, John. Again, that is a great question. Of course, by the way, the or by the mechanism, I should say, in which dexetacroplan works in geographic atrophy, we look forward to the readout from one year to two years. What we disclosed on that phase 1b study is a very small sample set of patients. It becomes, you know, very interesting when you start looking on an individual patient level even, but we are going to need the results from the larger studies to make a determination in that regard. All right. Fair enough, Cedric. Thanks a lot. Thank you, John.
spk14: Thank you. Our next question comes from the line of Madhu Kumar with Goldman Sachs. Your line is now open. Hey, guys. Thanks for taking our questions.
spk17: So I'll start with the PRINCE trial. How should we think about the PRINCE trial readout and what kind of impact it has on your P&H strategy and kind of how contingent is that on what happens at the PIDU for this?
spk02: Thank you so much for that question, Madhu. So the PRINCE trial, as we've mentioned many times before, is a Phase III clinical trial in treatment-naive patients with PNH that was very much designed to be there as an insurance policy. Because when we did the PEGASUS study, which was the Phase III clinical trial on which our approval is currently based, that was a study that aimed to do three things in one. First of all, to show that systemic pexitacoplant was a treatment for PNH. Second, to show that it would be superior to Soliris. And number three, to show that you could safely switch between the two drugs in either direction. And because that was a lot to handle for one trial, you know, we, of course, didn't know the outcome in advance. We wanted Prince to be there in case things would not go according to plan. Well, as it turns out, the Pegasus study gave us everything we had hoped for, and then some. PRINCE there is now to really give us a snapshot into patients with PNH that are from a much more uniform background. So not patients with PNH on treatment with Soliris that have, you know, what you could call suboptimal responses, but more representative of a broad population. And what we expect to see in PRINCE is, as we've seen in all of our studies so far, good control of PNH as measured in this case, by the measurement of lactate dehydrogenase control and stabilization of the hemoglobin levels.
spk17: Okay, great. So I'll follow up with a question you're probably not going to be able to answer, but I got to try. But really two questions. One, make the case for approval of PEG-Sytecaplan outside of post-Celeris treatment in PNH, based on the data you have so far? And then, to what extent do you think there is a case for approval broadly in PNH, given the kind of design of Pegasus and Ferroa and PADEC all together?
spk02: So, as you correctly assumed, we cannot comment on label discussions at this point in time, of course. since we are only two weeks away from the PDUFA. You know, we have commented in the past that we believe that in the Pegasus study, we showed good control of PNH in a long period of treatment-naive, I should say, monotherapy with pexetacroxane.
spk17: Okay. Then I'll have one go at a GA question. So, How do you think about dose frequency for GA and kind of the similarities and differences to the treatment of geographic atrophy as compared to, say, the treatment of wet AMD?
spk02: Thank you so much for that question, Madhu. So the two are very different manifestations of probably a similar underlying disease process. We've done a lot of work as it relates to understanding I'd say physician and patient receptivity to these two regimens, and I will hand the word to Adam in a minute as it relates to that. The bottom line is that currently there is no treatment for geographic atrophy, which is a debilitating and blinding disease affecting 5 million patients in the world. And it is a disease that when it will be treated will not have, I'll call it, the immediate feedback to the physician as you have with an anti-PHF treatment. that the exudates and the retina go away. So this is a treatment that will much more rely on the physician and the patients sticking to the prescribed regimen, as we will establish it hopefully in our phase three clinical trials. And where we are working on an artificial intelligence background, you will see much more about that at the ARVO conference as well, to be able to predict in patients with GA what is going to be the natural rate of photoreceptor cell loss in these particular patients, and what could a drug do in order to slow that down? So I don't know, Adam, if you want to add something as it relates to monthly versus every other month.
spk03: Yeah, thanks, Cedric. Thanks, Matthew. So, yeah, so obviously the one thing that drives excitement is that we have the chance of being the first approvable product in GA and currently no treatments. So we get some great responses from retina specialists when we speak to them around dosing. And they're along these types of themes, Madhu. So it's, you know, we get the, I think monthly dosing is fine. My wet AMD patients are motivated and I can see GA patients being equally driven. And we also get infrastructure comments, like we have the infrastructure to inject patients every month. So I think the excitement about a current treatment gives us great options as we progress, and I'm just looking forward to seeing the data come out towards the end of this year.
spk17: All right, great. Thanks for taking our questions, and I guess we'll hear from you all in a couple weeks.
spk02: Yes, thank you, Madhu.
spk14: Thank you. Our next question comes from the line of Yagal Notromovitz with Citigroup. Your line is now open.
spk08: Hi, Cedric and team. Thank you very much for taking the questions. I had two on GA. Regarding Derby and Oaks, if you get very good news in the third quarter and both the monthly and every other month end up being stat sig, what will be the commercial plan? Will you just move forward with the every other month since that's a lower treatment burden? Or is there any reason why you would also want to market the monthly regimen? And then my second question was if you could just explain the reasons why you're confident that the pegylation isn't causing the exhalations.
spk02: Thank you. Thank you so much, Miguel. Again, two very good questions. On geographic atrophy, I will again hand it to Adam. But it is worth mentioning that based on everything we have seen, I think it's reasonable to expect a dose response, if you want to call that. In other words, the efficacy for monthly is unlikely to be identical to every other month. So from that starting premise, that efficacy advantage would be something to take into account as it relates to commercialization. Adam, I don't know if you want to add something to that.
spk03: No, I think you said it very well. I think they're both important for us moving forward.
spk02: Thank you, Adam. And then as it relates to the regulation, so I think it is very important to point out that kind of the few publications that are out there that have looked at you know, polyethylene glycol as an agent that can promote, I'll call it exudations, in certain models are highly artificial models. So these are not animal models of macular degeneration. I'll give one example where they do a laser-induced ablation. So essentially you shine a laser in the retina and you induce a type of wound that is, you know, going to be very much driven by VEGF and where polyethylene glycol may have an effect on how that wound healing occurs. That is, of course, very different from what we see in macular degeneration, and we do not believe that the polyethylene glycol that is part of Vexeta Copeland has an effect on the exudates in our patients.
spk08: Got it. Thank you, Cedric.
spk02: Thank you, Yigal.
spk14: Thank you. Our next question comes from the line of Alethea Young with Cantor Fitzgerald. Your line is now open.
spk15: Thanks for taking my questions, too. Can you just talk, obviously, to the big market, but can you just talk a little bit about physician feedback and how they think about segmenting it, practically speaking, just in light of, you know, the study that you're running? And then just, you know, as it relates to the U.S. and Europe, as it relates to PEG-C to Copeland, you know, can you characterize, like, if there have been any kind of notable differences in, like, the EMA conversation versus the U.S. thing?
spk02: Thank you so much, Alethea. I will give the first part of that question again to Adam.
spk03: Thanks, Alethea. So, yeah, segmenting the GA market, obviously a very sizable patient demand there. So one thing we found that's been consistent is we expect the market to be segmented a little bit by GA size and location. So some of the clinical features that naturally resonate when you speak to physicians about treatment is is the lesion central or non-central, and how big is the lesion, small, medium, or large? And then you find that you apply some patient parameters to that segmentation, and that seems to be consistent. They also take into account bilateral GA, et cetera, and patients with wet A and D. So lesion size and location and patient demographic is the way that we can see the segmentation occurring within the GA market.
spk02: Thank you, Adam. And then as it relates to your second question, Alethea, so for questions related to the European commercialization and the regulatory path on systemic PXE-TACO plan and PNH and the other indications, I would ask you to speak with the SOBI directly. What I can tell you from our perspective is that this has been a fantastic partnership with no change in guidance as we set it out a couple of months ago.
spk15: Yeah, I figured it was worth a try. Thanks.
spk02: Thank you.
spk14: Thank you. Our next question comes from the line of Fiona Doe with Cowan & Company. Your line is now open.
spk11: On Derby & Oaks, in the past you've been very good about giving updates on missed visits as COVID has waxed and waned. With the trial trials drawing to a close, I'd be curious if you have any update on misvisits today. Are they still within the tolerances that you set out when you designed the trial, and any update on your discussions with the FDA over how misvisits, mismeasures are gonna be handled statistically in the study?
spk02: Yeah, thank you so much, Phil. So, as you correctly mentioned, of course, this is something that has been top of mind for us since the spring of last year, of course, and our guidance has not changed. So ever since the spring of last year, when I'd say the trial came under control, even with the subsequent waves, et cetera, the patient visits and the injections, which we track on a weekly basis, are where we wanted them to be. We have had regulatory interactions with the FDA, and without providing any specific comments, We feel that both trials are well-powered to make us meet our primary endpoints in the third quarter.
spk11: I believe at your analyst meeting, you discussed a change to the statistics or how they're going to be handled with misvisits. Am I mischaracterizing that? Are the statistics the same as initially designed, or has there been some sort of adjustment made for misvisits?
spk02: Yeah, we have not changed the statistical analysis plans. And, again, based on the control of the trial, we feel very good about the readout based on the existing SAP.
spk11: Perfect. Thank you. And then second question on P&H. I guess what are your most recent thoughts on pricing? What type of price would open up access the best or the most? And when will you disclose the price? Do you think you'll be in a position to disclose the exact price at the time of approval, or would you wait – until the launch actually begins in earnest. Thanks.
spk02: Thank you, Phil. I will hand that one over to Adam.
spk03: Thanks for the question, Phil. So, yeah, we're committed, as I said, to ensuring that every patient who wants Pexel to Coplin can have access, regardless of their ability to pay. So we've made sure that that patient access was the core of our pricing strategy in all of our work. So our pricing strategy involves benchmarking the clinical value that we believe that we can deliver to PNH patients. And we compared ourselves to the standard of care in PNH at the moment, so Soliris and Altamiris, as well as some other similar rare disease drugs. As we get closer to our potential approval, we'll finalize our pricing in terms of our label. And then post-approval, we'll start to... talk about the value that we believe that we can have for PNH patients. So more to come. Perfect. Thanks for taking my questions.
spk02: Thank you so much, Phil.
spk14: Thank you. Our next question comes from the line of Steve Seedhouse with Raymond James. Your line is now open.
spk05: Yes, hi. This is Timur Ivanov on for Steve Seedhouse. So thank you for taking our question. And so we have a question about Pegasus. Do you think Pegasus alone provides enough data to to prove that you have a robust effect on intravascular hemolysis since the primary endpoint was a change in hemoglobin? And then, relatedly, and I'm not sure if you can answer this, but has the FDA asked you to quantify the contribution to intra- versus extravascular hemolysis that texotacroplant brings?
spk02: Thank you so much for those questions, and nice to hear you. So, we are not commenting on the regulatory process at this point in time, again, since we are only two weeks away from PDUFA, but Pegasus as a study has been and is the only study included in this filing, which went through a proper pre-NDA meeting and the proper evaluations. So, the data contained in the Pegasus study is deemed sufficient to evaluate the efficacy of Pexitec of NMPNH.
spk05: Okay, thank you very much.
spk02: Yeah, thank you.
spk14: Thank you. Our next question comes from the line of Justin Kim with Oppenheimer. Your line is open.
spk07: Hi, good afternoon, and thanks for taking the question. You maybe touched on this a little bit, but with ARGO approaching near term, can you just discuss a little bit about how these tools and findings may influence your thinking on potential commercial use of texidicopalin and maybe even help enhance the development approach for next-generation compounds in AMD?
spk02: Thank you, Justin. That is an excellent question. So this is work that we're really very excited about. I mean, we have a lot of aspects coming up at ARVO, as you know, but specifically the work around the artificial intelligence is very important. And I think ultimately, you know, in a long-range planning context, being able to predict in a patient what the natural rate of progression of GA is going to be and what a patient and a physician could reasonably expect the drug to do obviously sets up an interesting framework for, you know, future pricing strategies. Adam, I'm going to hand it over to you if you want to comment beyond that.
spk03: You said it very nicely, Cedric.
spk02: Thank you, Adam. And I think, yeah, this is really something that we're very excited about. I think another piece to bear in mind here is that if you tell a patient with geographic atrophy, we are going to give you, for example, a monthly injection with pexitacopine intravitrally, I'm sure that in the first year there will be good compliance. But at some point, you know, when you forget to have an injection or you're on holiday, you won't see a difference. So to be able to retain these patients in the long run and being able to hopefully give them a good treatment for the long run is going to require something like this.
spk07: Got it. Great, great. And maybe just one question. On the Phase III MPGN C3G program, can you just discuss with us what steps remain, if any, before initiating the study, whether there's any sort of interaction with regulatory agencies, et cetera, required?
spk02: Thank you for that question as well. So as you know, this is, of course, a trial that requires close interaction and collaboration with our partner, SOVI, but the guidance on the start of the phase three has not changed. It will start in the second half of this year, and we are excited to explore Systemic Pixie Tackle Plan in those conditions.
spk07: Great, great.
spk02: Thanks very much. Thank you, Justin.
spk14: Thank you. Our next question comes from the line of Matthew Lucchini with BMO Capital Markets. Your line is now open.
spk16: Thank you. Good afternoon. So I think one for me would be just in the context, this is probably for Adam, in the context of geographic accuracy patient segmentation, I'd just be curious if you could talk a little bit about physician level of enthusiasm for treating earlier stage patients, those with Mason disease. I'm thinking, you know, in the context of the EU retina data from last year.
spk02: Thank you so much, Matthew. Adam, do you want to take that?
spk03: Yeah, thank you. Yeah, based on the segmentation that we discussed, we actually find that, and again, we used, in total transparency, our data used the Philly data when we did our market research, and we're obviously updating that. We found that actually there was a strong motivation driven often by the patient and supported by the retina specialists for understanding earlier use than we perhaps even anticipated. So again, if you look at our segmentation and you look at the lesion size being small and non-central, and you look at the central and small lesion size, you find that the physicians are motivated based on what we've seen in Philly, and I think they'll be even more motivated based on what we see in everything else that we're publishing at the moment, that there was a good groundswell for wanting to use the treatment earlier. So Again, we're excited to see the data towards the end of the year. So a good, good opportunity for us to help meet some unmet needs in GA.
spk16: Great, thanks. And then the second one, a little bit, perhaps hard to answer at this point, but, you know, assuming that geographic accuracy is successful, pexil copine would be, you know, presumably a fairly large Part B drug. And we'd just be curious to get your thinking around sort of, your approach to price, just your views on the evolving pricing dynamics coming out of Washington, you know, since Part B in particular and VEGF drugs, you know, tend to be particularly sensitive from a political perspective.
spk03: Adam, do you want to take it? Thank you. Absolutely. So, yeah, so you're right. We expect about 95%. OGA to be Medicare. We've done our initial pricing work and our value discussions, obviously, based, again, on what we're seeing coming out of Philly. And, I mean, it's super, super early for us. So one thing I will say that we have seen is that people naturally gravitate when you speak to payers, physicians, and taxpayers outside of the U.S., they naturally gravitate towards Lucentis and ILEA. as their first initial gut when it comes to pricing benchmarks for us to anchor on. Again, we have the same rationale as we have within P&H. We want to prioritize patient access. If our drug is as good as we hope it can be, then we want to make sure that patients have access to that. And we'll make sure that we'll talk about the value of treating GA patients. So definitely more to come, but you're spot on with your analysis of the access market. All right, thank you very much.
spk02: Thank you, Matthew.
spk14: Thank you. Our next question comes from the line of Joseph Stringer with Needham & Company. Your line is now open.
spk10: Thanks for taking our questions. I'll try another one on a potential P&H label. Maybe help us understand what a most favorable scenario would be and maybe a least favorable scenario. type of label would be. And I guess if you can sort of speak on that, on the details of that, maybe help us understand or put it into context, those two scenarios in terms of, you know, potential number of patients or, you know, the difference, how big the gap is between those two types of scenarios. Thank you.
spk02: Yeah, thank you so much, Joe. Again, we're not commenting on the label at this point in time since we are only two weeks away from PDUFA. Okay, fair enough. We're very happy to speak about that.
spk10: Okay, fair enough. Thanks for taking our question.
spk02: Thank you.
spk14: Thank you. Our next question comes from the line of Colleen Cousy with Baird. Your line is now open.
spk13: Hi, thanks so much for taking the question this afternoon. Starting with P&H, Adam, could you comment on how the early education is going for the sub-Q administration? Kind of any feedback you're getting on ease of use and how much education you think patients will need following approval?
spk03: Yep. Thank you, Colleen. Great question. So we're obviously going to make sure that we launch with a very robust patient services model. And we've been interacting with... P&H patients for the last couple of months to make sure that we understand their needs when it comes to that support and patient service approach. So as I said, we will have a good footprint to make sure that we can educate people about the unmet need about P&H treatment and also any support that they might need with administration through our Pellis care educators, as we call them, that will be there to help the P&H patients. One thing we found is that actually patients have responded very well to the ability to have treatment at home, and the COVID scenario has amplified that. We found some great methods where we believe that, again, through face-to-face interactions where allowed, but also virtual interactions, that we can support patients incredibly well with our administration. And we're very much looking forward to doing so.
spk13: Great. Thanks. And then on Derby Oaks, just procedurally, will all of those patients remain randomized and blinded out to 24 months, or will the study be unblinded at the 12-month readout? Just thinking about how the recent Phase 1b data continued to strengthen out to 24 months, I'm just wondering if we'd be able to see that play out in the Phase 3 data.
spk02: Thank you, Colleen. Patients will stay randomized. Fede, I don't know if you want to add something to that.
spk18: Yeah, that is the simple answer. So the study will continue to be double mask, and the patients will continue on the randomized schedule all the way to 24 months.
spk13: Great, thanks.
spk14: Thank you. Our next question comes from the line of Laura Chico with Webless Securities. Your line is now open.
spk12: Thanks very much for taking the question. Adam, I thought the commentary around launch prep was actually pretty helpful. And sorry if I missed this, but I'm just curious, what is the size of the expanded access program at present? And what proportion of those patients are within the US?
spk03: Thanks, Laura, for the question. I'll actually hand the expanded access program over to Dr. Federico Grossi.
spk18: Well, we opened our expanded access program in the U.S. for now to help the patients with high medical need to receive Pexet or Coplan while the drug is or the application is being reviewed by the FDA. We don't expect the AP program to affect our commercial metrics or revenue. And this goes to Peru for we're not commenting any further on our early access program.
spk12: Okay. Okay. That's helpful. Maybe one other question then. I think the latest 10Q continues to point towards cash runway into the second half of 22. I'm just wondering if you could elaborate a little bit more on the levers there that could either contract or extend that runway a bit and just against the backdrop of Derby and Oaks, the primary endpoint reading out the third quarter of 21. The studies do run for two years or so, so in the 3Q of 22. So just trying to understand how the spend in the studies might change after that primary readout or how we should be thinking about that. Thanks.
spk02: Thank you, Laura. Tim, do you want to take that?
spk04: Sure. Thanks, Laura. Yeah, that's a great question because actually that calculation around cash runway contemplates a GA success scenario wherein we built up our global launch capabilities and also moved forward in other studies related to Peg C to Copeland intravitrally. So ultimately, you know, the calculation becomes very different if GA were not to be successful and we were not to move forward and our cash runway would get extended quite a bit beyond that. Aside from that, you know, the typical things relate to, you know, how we perform on the, you know, in terms of our commercial launch and P&H pretty much. So I hope that answers your question.
spk12: Thanks, Chris.
spk02: Thank you so much, Laura. Well, thank you all for joining us on our first quarter conference call. We look forward to our May 14th PDUFA date in PNH, and we are excited about the transformational year ahead for APDs as we continue to build our global leadership in complement. Thank you again so much for joining us today.
spk14: Ladies and gentlemen, this concludes today's conference call. Thank you for your participation. You may now disconnect.
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