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spk19: Ladies and gentlemen, thank you for standing by and welcome to the second quarter 2022 earnings call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you need to press star 1-1 on your telephone. I would now like to turn the call over to your host, Meredith Kai. You may begin.
spk11: Good afternoon, and thank you for joining us to discuss Appellus' second quarter 2022 financial results. With me on the call are co-founder and chief executive officer, Dr. Cedric Francois, chief commercial officer, Adam Townsend, chief medical officer, Dr. Federico Grossi, and chief financial officer, Tim Sullivan. Before we begin, I would like to point out on slide three 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'll turn the call over to Cedric.
spk22: Thank you all for joining us today. 2022 is a transformational year at ATHELIS, and we are making great progress across each of our key priorities. I'll start with geographic atrophy, or GA. A few weeks ago, we were thrilled to announce that our NDA for Intravitreal Tax Data Co-Plan was accepted by the FDA with a priority review designation and the PDUFA date of November 26, 2022. The FDA also stated that it is not planning to hold an advisory committee meeting to discuss the application. This is the best outcome we could have hoped for, and I am so proud of the Afghani's team for their efforts in getting us to this pivotal point. The NDA includes all available data from our Jerby and Oakes studies out to 18 months. and in the case of some patients, even longer, as well as the 12-month data from our Philly study. Collectively, these data reinforce the potential for Vexita Copeland to meaningfully slow disease progression and become the first-ever treatment for the millions of patients living with GA, a relentless disease that is a leading cause of blindness worldwide. We continue to work with the agency in our efforts to bring this therapy to patients who currently have no approved treatments. In parallel, we are also ramping up our commercial preparations so that we are well-positioned to bring intravitreal pexetacroplan to patients immediately upon potential approval. In Europe, we are on track to submit our application to the EMEA by the end of this year. We will include the 24-month data from Derby and Oaks in our submission, which we plan to report in September. J.D. will speak to this a bit more in a few minutes. Turning to PNH, we remain focused on further establishing Empavedi as a first-line treatment for patients living with PNH. We are seeing continued strength across a number of key indicators, translating to $15.7 million in U.S. net revenues for the second quarter. Globally, our partner Sobe is also making progress in bringing Empaveli to patients with PNH outside of the U.S. Beyond PNH, we continue to advance Empaveli as a transformative therapy for rare, complement-driven diseases. Together with Sobe, we now have four later-stage clinical programs underway. We are also continuing to progress our early stage pipeline with IND's plan for APL2006 and our siRNA program in the first half of next year. We have made great progress in our partnership with BEAM and with our efforts to advance complement inhibition as a novel approach to enhancing adeno-associated viruses or AAZ-based gene therapy products. We are also continuing to advance our preclinical work with APL 1030 for potential use in neurodegenerative diseases, but no longer expect to submit the IND by the end of 2022. On the finance side, we ended the second quarter with approximately $850 million in cash, providing runway into the first quarter of 2024. This puts us in a uniquely strong position in this challenging market environment as we head into a potential launch later this year. We look forward to building on our momentum as we further cement our position as a leader in complements across multiple therapeutic areas. And with that, I will turn it over to Adam.
spk09: Thank you, Cedric. Turning to slide five, we are now in our second year of commercial Empaveli in the U.S., and as Cedric mentioned, the commercial launch remains strong. In the first year, we focused our efforts on the patients with the highest unmet need, who are the one-third of patients on C5 inhibitors who require transfusions to address their falling hemoglobin levels. We are continuing to see positive trends across the key leading indicators. In the second quarter, approximately 30 start forms were generated, bringing the total number of start forms since launch to approximately 190. Over 75% of C5 inhibitor patient switches are continuing to come from Altamiris. Over 35 additional physicians were REMS certified, bringing the total since launch to greater than 200. we continue to see strong REM certification growth, which continues to be a key leading indicator as we move into the second year of launch. Patient compliance rates remain high at 95%, and we have established strong formulary access amongst the top 20 payers. Now, in the second year, we are heading into the next phase of our commercial strategy. which is expanding our focus to the broader PNH community by further positioning EmperBelly as first-line treatment for all patients with PNH. We are refining our physician targeting so that we efficiently call on those prescribers who are treating the majority of PNH patients. We are also advancing our outreach to key thought leaders, especially now that Dr. Hillman is fully onboarded. In this next phase of launch, we will evolve our partnerships with new centers to drive additional prescribers and ensure that patients with PNH have access to Empaveli. Additionally, our SNDA, including the Phase III PRINCE results and the 48-week Phase III PEGASUS data was accepted with a PDUFA date in February 2023. If approved by the FDA, This will allow us to strengthen our promotion of Empaveli for treatment-naive patients and raise more awareness of our long-term efficacy and safety data. Now turning our attention to our progress in GA on slide six. We are excited to be even closer to our anticipated approval and commercial launch in this critical area of high unmet need. GA impacts 5 million people worldwide, including 1 million people in the US. And I expect that the first approved therapy for this devastating disease may uncover even more patients. Here at Apellis, we are compelled by the potential to bring the first ever treatment to patients as quickly as possible, and excited by the FDA's decision to grant intravitreal pexetocoplin a priority review designation. We are eagerly awaiting our November PDUFA date, and our team is focused on ensuring that we are well positioned for the launch. We are ramping up our commercial capabilities with the key U.S. leadership positions already in place, as well as additional key positions globally, and much of the U.S. field force is starting imminently. Our focus prior to approval is on disease state awareness specifically within the retinal community and among some of the broader eye care groups. We are also advancing payer engagement to help us to secure strong reimbursement and access post-approval. And we have established a Retina Advisory Council made up of several global opinion leaders to provide insights and advice as we prepare to bring pexetocopin to the market. At launch, our initial focus will be on the top 2,600 retinal specialists and injecting ophthalmologists in the US. These physicians are managing the vast majority of GA patients currently. We will expand our efforts over time to activating additional referral pathways to ensure that GA patients are being referred to the right physician for treatment consideration. We look forward to providing more granular details on launch preparation and execution as we get closer to our PDUFA date. Let me now turn the call over to Fede.
spk16: Thank you, Adam. The data from our Derby and Oaks studies continue to underscore the significant potential of our C3 complement approach. Following the 18-month data reported in March, we have shared additional analysis at key retina meetings, reinforcing that treatment with both monthly and every other month intravitreal Pexetacoplan in these studies demonstrated a clinically meaningful reduction in GA lesion growth with a favorable safety profile. As highlighted on slide seven, at ARBO in May, we presented data showing the treatment with Pexetacoplan continued to demonstrate a robust effect in patients with extra further lesions, and an improved effect in patients with further lesions as compared to what we observed in the 12-month results. We also had a strong presence at macular society in June. This included data showing consistent reductions in GA lesion growth in treated eyes versus untreated fellow eyes. Texas Copeland also demonstrated sustained reductions in GA lesion growth across all subgroups defined by increasing distances from the foveal center. And just last month at the SRS, we shared analysis from Derby and Oaks that showed the mean rate or slope of GA lesion growth at 18 months. The results from this analysis were consistent with what we have shown previously at 18 months, with all nominal p-values for both dosing regimens below 0.05. Collectively, all the data from Derby, Oaks, and Philly reinforced the potential of pexetocoplan to slow the progression of GA across the disease spectrum, which is critically important given the heterogeneity of this patient population. We're excited to potentially bring the first ever therapy to patients with GA with an opportunity to save as many photoreceptor cells as possible throughout the course of the disease. In September, we plan to share top-line results from Derby and Oaks at 24 months. As you may recall, at 18 months, we presented pool data showing that treatment with pexetacoplan resulted in increased efficacy over each six months interval, zero to six, six to 12, and 12 to 18. We look forward to evaluating whether these improvements continue between month 18 to 24. If confirmed, it could mean that the longer patients are on treatment, the better the response to the drug. This could compound into very large lesion size reductions over time. Additionally, the secondary functional endpoints will be assessed at 24 months. GA progression is correlated with loss of visual function over long periods of time, meaning that reducing the rate of GA lesion growth should eventually reduce the rate of vision loss. As we have mentioned before, and as literature will suggest, we do not expect to detect a difference between Pexet-Coplin and sham at 24 months due to the limitations of the functional endpoints and the relatively short period of time over which they are being assessed. We anticipate the separation to occur over longer periods of time. We will include this 24-month data in our MAA. We have had productive discussions with the rapporteurs to date and are on track to submitting to EMA by the end of 2022. The rapporteurs have shared with us that the EMA wants to understand the relationship between preserving visual function and reductions in GA lesion growth. We're confident in our ability to show this based on published natural history studies and data from our Phase III studies. Moving on to our pipeline on slide eight, we're also working to deliver on the broad platform potential of Empaveli to advance a rare disease franchise, which includes four later stage studies in multiple complement-driven diseases. In May, we dosed the first patient in a Phase III study with pexetacopalin in immune complex membranopluriferative glomerulonephritis, or ICMPGN, and C3 glomerulopathy, or C3G. We also learned that FDA granted orphan drug designation for pexetacoplin for the treatment of ICMPGN. This designation had previously been granted for pexetacoplin for C3G. The Phase II study in hematopoietic stem cell transplant-associated thrombotic microangiopathy, or HSCT-TMA, is actively enrolled in patients. Our partner, SOVI, is currently screening patients in the phase three study in collaglutinin disease, or CAD, and has guided to now dosing the first patient in the second half of 2022. And finally, we remain on track to report the top line results from our potential registrational phase two study in LS in mid-2023. Let me now turn the call over to Tim for a review of the financials.
spk06: Tim? Thank you.
spk20: Since we issued a press release earlier today with the full financial results, I will just focus on the highlights for the second quarter of 2022 summarized here on slide 9. Total revenue was 16.3Million, which consisted of 15.7Million in MPVELE net product revenue and 0.6Million in collaboration revenue from SOBE. R&D expenses were 102Million, G&A expenses were 63Million, and we reported a net loss of $156 million. As of June 30, 2022, Pellis had $853 million in cash, cash equivalents, and short-term marketable securities. We expect our current cash balance to fund our operations into the first quarter of 2024, including the ongoing MPA Valley launch, the global launch of Pegasita, Copeland, and GA, and further development of our pipelines. We remain confident in the Pellis' financial future as we continue to execute on our upcoming milestones. I will now turn the call back over to Cedric for closing remarks. Cedric?
spk22: Thank you, Tim. We are excited about the many opportunities ahead. By year end, we will expect to advance our position as the global leader in complement with two commercial products and a robust pipeline encompassing multiple late-stage rare disease programs and additionally preclinical programs heading into the clinic. We look forward to continuing to share our progress as we build on the company's momentum. Let us now open the call for questions. Operator?
spk19: If you have a question or a comment at this time, please press star 1-1 on your phone. We'll pause for a moment while we compile our Q&A roster. Our first question comes from Madhu Kumar for the Goldman Sachs. Your line is open.
spk04: Hey, everyone. Thanks for taking our questions. So I guess two from us. So the first one is a question we've been getting a lot recently from investors is how to think about some of the disclosed ischemic optic neuropathy events that were mentioned in the Orville presentation a few months ago. So how are you guys thinking about ION and how are you thinking about it in terms of kind of the ongoing review process for PEG and GA? Second question we've been getting a lot of from investors is how to think about the recently passed drug pricing reform as part of the Inflation Reduction Act that happened over the weekend. How do you think that impacts a drug like Pegs that said to Copeland that is largely biased towards patients on Medicare and elderly patients and has kind of like a big market opportunity framework? So any visibility on those two points would be greatly appreciated. Thanks.
spk22: Thank you so much, Madu, and great to hear you. So first of all, on the ION cases, so no assays for ischemic optic neuropathy were reported between the 18 and the 24-month time point. So as you may recall, between the two studies, we had one case between month 6 and 12 and two cases between month 12 and 18, where, again, the patients that were subjected to this also had, you know, kind of comorbidities that could explain why this happened. But it's something that we continue to track, but we were very happy to see that it does not occur again, and it's not something that we are concerned about at this point in time. I'm going to hand it over to Adam to talk briefly about the pricing.
spk09: Thanks for the question, Matthew. So obviously we're monitoring this quite closely, but we believe the direct impact on Appelluses' portfolio is currently pretty limited. And let me explain a little bit. our thinking. So let's start with Emper Valley, right? So Emper Valley, we don't think can be subject to negotiation until 2030 at the earliest. And even then, we think it's probably unlikely that Medicare spending on the drug would be sufficient to result in CMS seeking to negotiate a price for the drug. As a reminder of our current sales, Medicare only represents 25% of the current business. Now, obviously, with future indications and the extent of the Medicare spend, we determine the likelihood of eligibility for inclusion or negotiation in the future. Now, if we move to GA and intravitreal PEG, based on the most recent bill language, again, the drug would not be subject to negotiation until early 2030s at the earliest. Obviously at the moment, we can't determine the likelihood of negotiation until later in the 2020s when we have some more data on the spending on PEG in GA and how that compares to other Medicare products. What is interesting is obviously currently our composition of matter patterns for PEG expire in the early 2030s. So even with a negotiated price potential, it would only really have an impact for two to three years until our As I said at the beginning, I think at the moment, as we can see the bill, we believe the direct impact on our Pellis and our portfolio is currently limited.
spk04: Great. Thanks for taking our questions.
spk19: And one moment for our next question. Our next question comes from . With Evercore, your line is open.
spk21: Hi, guys. Thanks for taking my questions. Maybe a couple of them, if I may. First, could you clarify, and I know there's been a lot of confusion on this, could you clarify any cases of vitreitis, uveitis, or ion in Phase II Philly trial that may not have been in the presentation? And I think there's one case in Cham, for example, if you could speak to that. And then secondly, folks listening in, I know there's been a lot of interest in understanding the profile on the clouding side for BofU from their Phase 3 experience, if you could speak to any observations along those lines from your data to date. And I'm specifically referring to the occlusion scene in BofU, and if there's anything like that. Thank you very much.
spk22: Thank you so much, Igor, for that question. So in Philly, we had a case of ION and the sham control in the untreated fellow as well. And that's, as I already mentioned in the previous question, ION is something that does occur naturally in an elderly population, and it appears to be something that occurs more commonly when patients receive intravitreal injections, something that we know also from the patients that are on treatment with anti-VEGF. Also, the cases of vitreitis go hand-in-hand with the intraocular inflammation background that we have for this intravitreal administration of pexetacoblan. And the IOI cases that we have, first of all, on a qualitative basis, are different from what we see with BOV, where, you know, really the types of IOI that we had or that you have with that therapy can be very destructive to the eye. The profile that we have seen for the cases of inflammation are first of all, quantitatively very low and in line with what you would expect from patients on intravitreal treatment and also not of the kind that we are concerned about. So we believe that the safety profile, you know, continues to be very favorable and look forward to reporting 24-month data soon as well.
spk21: And Cedric, would you guys be able to speak to vision loss with any of these cases when the 24-month data comes out? I don't want to put you on the spot right now.
spk22: Well, I mean, look, we will, of course, you know, elaborate more on the safety profile, including on, you know, what exactly the impact of these cases are. When exactly we will do that remains to be determined, so I'm not sure we'll do that in the top line unless it's considered meaningful, but definitely in the future we'll talk more about that. Thank you.
spk19: One moment for our next question. Our next question comes from Andrew Palmarama with J.P. Morgan. Your line is open.
spk06: Hey, guys. Thanks so much for taking the question, and congrats on all the progress, particularly on the GA side. I wanted to ask a question on the 24 Derby and Oaks upcoming on back of some of your opening comments. So in a note last week, we had that sort of Pexita-Copeland preservation of the community relative to basements. and or a couple letter bit relative to SIBO as kind of a win scenario. Thank you so much for that question.
spk22: So we look forward to the 24 month data. In September, as mentioned, on the functional endpoints, as we have always said, we believe that those endpoints, well, we know that those endpoints are not relevant to the FDA, and the reason for that is that measuring functional endpoints is very difficult to do, is very variable, and takes a long time to manifest itself on a baseline, or let alone when you are on treatment. So it all comes down to seeing the correlation between reduction in lesion growth and showing that you save photoreceptor cells and estimating how, in the long run, that will actually impact the functional endpoint. So we'll be working on that. The, you know, so we expect it to be in line between at 24 months to not show a difference yet, at least not statistical, and we believe that that will have no impact on the FDA approval process.
spk06: Thanks so much for taking our question.
spk19: Thank you. And we'll move on to our next question. Our next question comes from Kazeena Med with Bank of America. Your line is open.
spk14: Hi, guys. Good afternoon, and thanks for taking my question. As it relates to dosing frequency, is every other month still something that's realistically on the table as far as your discussions with the agency? And do you think that physicians having flexibility to dose either once a month or once every other month is gonna be important for commercial uptake? And then secondly, can you just give us an update on where you are with ramping on the commercial front in terms of hiring people and when they would be trained and would you be ready to go on day one if you got approval in November? Thank you.
spk22: Thank you so much, Tazi. So not only is every other month on the table, it's a product profile that we are very excited about. So when you look at the efficacy profile that we reported at 18 months, we'll see what happens at 24, you get a lot of the benefits, maybe as much as 90% of the benefits with every other month injections, every other month treatment with half the number of injections. So something that is very exciting to us, something that we will continue to evaluate. To get to your point on the competitive profile, you know, we have several elements that position us favorably competitively as well. First one, of course, again, the ability to dose every two months. Secondly, the fact that we have reported all of the data to the FDA all the way up to 18 months with, I think, a reasonable expectation that should we get approval, that that will be included into the label. We also have, of course, both foveal as well as extra foveal patients that were included, so a broad patient population, all of which we look forward to talking about more. I'm going to hand it over to Adam to talk briefly about what we are doing in terms of commercial prep.
spk09: Hey, Tazine, it's Adam. So, thank you for your question. So, yes, we are ready to go. We started to look for all of our field-based teams prior over the last couple of months, and we are now in the process of onboarding all of them. So a quick step back. Prior to this great news, we had hired the high-level leadership roles within the U.S., the high-level leadership roles within Europe and the rest of the world. And now we're going through all of the training process over the next couple of weeks to fully onboard the field-based teams from a medical affairs perspective and a market access perspective as well and any more sales and marketing people. We had a huge amount of interest in people wanting to join our company, which is super exciting. And obviously, we are getting ready for our November Purdue for Day. And the second part of your commercial ramping question was, are we going to be ready at that time? And the answer is absolutely, that's our plan. I mean, with a high unmet need in GA, we're going to do everything that we can to be ready immediately post that PDUFA date. So the team's exactly where they need to be today.
spk14: Thank you.
spk19: One moment for our next question. Our next question comes from Layla Youssef with Cowan. Your line is open.
spk01: Hi, thanks so much for taking the question, and congrats on the progress. Maybe quickly on the European filing expected by the end of the year in GA, can you quickly clarify what else is outstanding besides the 24-month data for that? Is any component of that maybe dependent on feedback from the FDA? And then maybe as a quick question, Appreciate that the FDA didn't request an adcom currently, but what is your kind of understanding of the last possible deadline that they would have to essentially change their mind and request an adcom given the timing of their current stupa? Thank you.
spk22: Thank you so much, Laila. So it was a little bit marbled, but I believe that you asked about the European submission and including the 24-month data, which is what we are indeed going to do, and we plan to file before the end of the year. I'm not sure whether you had a question more specific to that.
spk01: Oh, yeah. If there is anything else that was outstanding or if you're waiting on feedback from the FDA, that could help change that timing.
spk22: No. So this is not linked to feedback from the FDA. It's just including the 24-month data. And then as it relates to the no outcomes, so... You know, I believe from my understanding that up to six weeks before the PDUFA date, you can have an adcom. You know, I think that considering the very tight timelines that we have, that of course the longer Time goes by, the less favorable time becomes to still organize an outcome. And so far, we have not received any indication that there would be one. I think it's also worth mentioning that feedback that we gave as it relates to the regulatory communication was done in writing and is to the best of our knowledge, of course.
spk01: Gotcha. Thank you very much for the color.
spk19: How about next question? Our next question comes from Steven Seathouse with Raymond James. Your line is open.
spk18: Yeah, hi. Thanks for taking the question. Just from a statistical analysis plan standpoint, when the FDA reviews the GA submission, is the primary analysis 12 months in all three studies or 18 months in Derby and Oaks. And just given the availability of the 18 month data in the filing, are you still sort of needing to specify that Philly and Oaks are the two positive well controlled studies or do all three studies fit that criteria now?
spk22: Yeah, thank you so much Steve. The FDA does consider the primary analysis endpoint at 18 months in Derby and in Oaks. In Philly, of course, the treatment was up to 12 months, so there it was at 12 months. You correctly point out that it was very important to us to get an adjudication on Philly in November last year. It gave us confidence and also allowed us to prepare the NDA really without spending a lot of time trying to understand Derby and with the confidence that over time, Derby would catch up to the Oaks trial. And that is what we saw happening at the 18-month data standpoint, where, of course, the p-value is flipped. And we will continue to see what happens at the 24 months, whether that correction continues to take place.
spk18: Okay. And then just quickly, for APL2006, what precisely is the indication or eligible patient for that product? Is it just wet AMD?
spk22: So we are going to be talking about that more in the future. For those on the call that are not familiar with this product, this is something that combines an anti-VEGF with an anti-C3 active moiety in a single molecular entity. So it will be something that we believe will become very valuable in the context of early treatment, either for wet AMV or geographic atrophy, but how we are going to approach this from a regulatory development perspective remains to be determined.
spk18: All right, thanks very much for the question.
spk19: And one moment for our next question. Our next question comes from Christopher Harrington with Jefferies. Your line is open.
spk08: Hi, Cain. This is Combison for Chris. Maybe on kind of the N-Fidelity label expansion opportunities, can you help us understand the mechanistic differences between ICMPGN and C3G? What proportion of the post-transplant patients have recurrent disease? And do you expect Ensoveli will perform as well in more severe patients as opposed to kind of more moderate patients? And then maybe as a second indication, for ALS, can you help us understand the CAF score endpoint and what will be important to demonstrate in terms of survival time and then in terms of ALS function rating score? Thank you very much.
spk22: Thank you, Colby. So on the C3G indication, so we kind of think about the C3G, and for that matter, the IgM-BGM population in kind of three buckets. The first one is newly diagnosed patients, typically adolescents, you know, still with well-functioning kidneys, but with, of course, a path towards kidney failure. The progression of the disease typically means that over the course of 10 years, half of your patients will go into end-stage renal disease. So that's, of course, when you're in your teens, not a lot of time. The second bucket of patients, therefore, are those that are having significant loss of renal function, sometimes with nephrotic syndrome, and those are patients where efficacy becomes crucially important to avoid, of course, dialysis or let alone transplantation. And then to your point, the third category of patients are those that have been transplanted and where recurrence, again, is something that occurs in more than half of the patients and something where we believe we can have an influence in avoiding that from happening. Then as it relates to ALS, so the primary endpoint that we have there is a combined assessment of function and survival. This is an endpoint that was discussed not just with the US regulators, but also internationally. And the study is, it's a registrational phase two clinical trial. So, you know, it is properly powered should it have a positive readout to hopefully allow us to file in the various jurisdictions.
spk08: Great, thank you. And maybe as one quick follow-up, is there any lessons you can learn from kind of the systemic administration for ALS that you may be able to apply to your intrathecal neuro programs or nothing there. Thanks again, and that's my final question.
spk22: Yeah, so I think, look, as many of you know, anti-C5 has failed before when Lutomiris was tested in patients with ALS, but we also all know that C3 does many things that C5 control does not do. I mean, we show that very clearly, of course, in PNH, and it was the source of our approval there. with Empaveli. We are now well north of 600 patient years of dosing with Empaveli, and I think, you know, and it's a point that we will be talking about more, is we haven't seen a single case so far of meningococcal infection, not one. Whereas at this point in time, should he have been on a C5 inhibitor, it's probably reasonable to have expected in the range of three cases, if not more. So that is something that, you know, we're very excited about. I think it's a safety profile that is building as we get more patients on active and something that should we have a positive result in ALS or the other indications where we're testing will, of course, be very beneficial as well.
spk19: Thank you. One moment for our next question. Our next question comes from Colleen Custey with R.W. Baer. Your line is open.
spk15: Hi. Good afternoon, and thanks for taking our questions. As a follow-up to Steve's question earlier on the 18-month data, based on any feedback you've received from the FDA, how do you see the 18-month data fitting in to the filing, I guess, specifically as it relates to the 12-month data?
spk22: I think that – thank you, Colleen, for that question. So it was very important for us to include the 18-month data, right? So when we got the readout in September, and of course the disappointment over narrowly missing the primary endpoint in Derby, we had two important strategic steps that we took. The first one was to get that adjudication in Philly that we got early November. The second one was our decision in January to go to the FDA and to propose in our pre-NDA meeting that we would include the full analysis for safety as well as efficacy all the way up to 18 months, hoping that there would be a catch-up of Derby to Oaks. And as you know, that is indeed what happened, right? So data up to 18 months was submitted, and the primary endpoint interpretation was very important with that 18-month data in mind. just create a very complete picture for the FDA. I think it was a good decision to do that. Create a very complete picture for the FDA. I think it was a good decision to do that. I'm not sure that answers your question, Colleen.
spk15: Yeah, great, thank you. Are there any avenues that you're aware of that the FDA has available to get feedback from industry experts outside of a formal adcom? Or if there's no adcom, how should we assume there's kind of no interaction between the FDA and the field during its review?
spk22: Yeah, so look, I think with the ophthalmological division at the FDA, we have a a very well-informed and well-run division that has been stable for a very long time. The leadership there has been there for, I believe it's now three decades. And I know for a fact that this is a division that has a very deep interaction with the key opinion leaders in this field. The reason why there was no outcome, I'm not going to speculate on. We believe that the filing was straightforward based on the content that we submitted, and it seems that they agree with us. But we also know for a fact that there's lots of interactions that happen offline in this very tight-knit community.
spk15: Got it. That makes sense. Thank you. And last one for me. Just on the manufacturing part of the filing you submitted, can you just make any high-level comments there and when the CMC inspections might occur?
spk22: Yeah, so the manufacturing of the drug substance is the same as it is for N-Bavilli, right? So it's Vexita-Coltan. As you know, we got our approval for MPAVETI without a single 483 issued on either GCP or on manufacturing. We don't know if we will get inspections on the manufacturing side or not, but should we have any, we feel very comfortable that we will be able to come out of those positive.
spk15: Great. Thanks for taking our questions.
spk19: Thank you. One moment for our next question. Our next question comes from Derek Archilla with Wells Fargo. Your line is open.
spk05: Hey, good afternoon, guys. Thanks for taking the question. Just two from us. The first, I just wondered if, you know, has the FDA discussed with you any potential findings, either safety or efficacy, from the 24-month data set that might prompt an adcom or require the 24-month data to be submitted as part of the review? And then one question on TNH. I guess, how are you tracking the plan, you know, in the launch? And I guess, you know, what are the major benefits of the inclusion of the 48 Pegasus in the PRINCE data? Like, what issue is that addressing, you know, in the launch thing?
spk22: Thank you, Derek. I will hand over the P&H question to Adam. But as it relates to the 24-month data, I think it's important to note that we don't expect any surprises between 18 and 24 months, right? So we believe to see an extension of both the efficacy as well as the safety profile as it was established at 18 months. So I think that is the way the FDA looked at it. That's the way we look at it. Of course, should something unexpected emerge at that point in time, it's hard to know what action should be required or what we would do, but that's not something that we believe will be the case. And then for P&H, I will hand it over to Adam.
spk09: Thanks, Derek. Yes, so obviously we're entering year two of our launch, and internally we've now pivoted to strategy, what we call phase two, right, where we're starting to target new centers and new physicians and continue to drive those sources of demand. And we'll keep talking about start forms and switches from C5s and REM certifications, et cetera. The 48-week print date just really solidifies our first-line treatment of choice for PNH, right? The more data that we can have in the label, the more robust conversations we can have with physicians on the long-term efficacy and safety, but also on treatment naive. We're making a really good inroads with treatment naive patients, and I'll give you a little insight. Our July start forms, over a third of our July start forms were treatment naive patients. We continue to see growth as physicians start to broaden their use from those with the highest unmet need to those larger and broader PNH patients and treatment-like patients. And I expect to see that continue to progress and accelerate as we enter the next phase of our launch. So that's how the PRINCE data and the 48-week Pegasus data help us out. Great. Thanks so much for answering the question.
spk19: And one moment for our next question. Our next question comes from Justin Kim with Oppenheimer. Your line is open.
spk07: Hi. Good afternoon, and thanks for taking the question. Just maybe one question from us. You know, I know that the 24-month data may not be sort of that point where you can see separation on visual acuity, but, you know, how should we think about gale and sort of that sort of duration of treatment as you combine it with potentially derby and noves? Is that something, you know, that could show maybe that hint or trend or separation? Just wondering, you know, how would you think about that study?
spk22: Yeah, thank you very much for that question, Justin. So Gale is something that we are incredibly excited and happy with, right? So for those not familiar with that, it's a three-year extension on the patients from Derby and Oaks that we then enroll to continue to monitor how function and how lesion size reductions and safety profile themselves over time. It's also something that's very important to us competitively. Again, we have every other month dosing. We have our first mover advantage. We have 18-month data and the filing. includes all types of patients with foveal as well as extra foveal patients. And then, again, the ability to look in Gale as to what happens in the long run. So it's something very important to us that we will talk about in the years to come.
spk19: Great. Thanks so much. Thank you. One moment for our next question. The question comes from Yago Natrona, Bridgewood City. Your line is open.
spk03: Oh, hi. Great. Thanks for taking the question. I think, Federico, you said that the EMA wanted to see the relation between preserving visual function and lesion growth. So could you just expand a little bit on what data specifically you're going to leverage to make this point to EMA, since you said that the 24-month update won't be sufficient to show the separation on the functional endpoints? Thanks.
spk17: Thank you for the question. So when we refer to the 24 months not being something significant, that means that may not be sufficient to show trends on the data. So we're going to look at what we get from the study and in addition to that all the natural history data to find the relationship between the functional endpoints and – sorry, between the anatomical endpoints and function. that not necessarily may come from central visual acuity, which is hard to measure. So we're going to be doing a little more investigation of the data in the study to see what correlations we get.
spk03: Okay, thanks. And then just, Adam, could you just tell us, if you could, what percent of the P&H market you believe you've captured so far in the U.S.?
spk09: Yes, so thanks, Miguel. Obviously, we think there are 1,500 C5-treated patients, and we have over 200 start forms, approximately 190 to 200 start forms. So that should give you a good hint of the progress that we're making as we go. We obviously don't give guidance on revenue or anything along those lines. With over 200 REM-certified physicians and start forms continue to come in, we think we're really making good progress in converting C5 patients and starting treatment-naive patients within PNH.
spk19: Okay. Thank you. One moment for our next question. Our next question comes from Ellie Murrell with UBS. Your line is open.
spk13: Hey guys, thanks so much for taking the question. Just first on the ION, can you just elaborate on the cases that were seen? I guess how the patients presented and how they were managed and I guess if it was resolved. And then also specifically, I think in one of the first questions on the call, you mentioned some comorbidities that the patients had. If you could just kind of elaborate on this and maybe why this sort of leads you to think that this was not drug related in those cases seen. And then just second question, just in terms of thinking about the real-world potential duration of use of anti-VEGFs in the cases of sort of new-onset exudation, maybe just, you know, how you're thinking about that and, you know, how long anti-VEGFs might be used in those cases. And I guess if there's any data that we can expect, such as from the 24-month data or, you know, I'm thinking about sort of the longer-term scale study about sort of the management of the new-onset exudations and thinking about the duration of use of the anti-VEG app. Thanks.
spk22: Thank you. So on the ION cases, you know, the details is not something we're going to talk about on this call. I think the first and important point was to find out if these SAs, you know, were becoming worse over time, right? I mean, we had one from 6 to 12 and then two from 12 to 18. You know, there was, of course, I think your rightful consideration is it's going to become worse or not, and it didn't, right? So we didn't have a single additional case. Now, as it relates to the real-world evidence for the new onset exudations, the DERBY and OAKS studies, when patients have new onset exudations, they get treated with anti-VEGF on regular pathology. At the end of the two-year time period, we have one PRN step. What does that mean? People stop receiving anti-HF, and then we find out how long does it take for these patients to leak again. And we compare that between active and the sham control. So that's going to be an interesting piece of information on which we will have more information next year as well. So Gail is important there again to find out what that means, how dependent patients are going to be on anti-HF, But I can tell you that in the studies, the combined administration of anti-VEGF and pexitacobin has not been an issue.
spk13: Great. Thanks for the call, Eric. Thank you.
spk19: I'm going to move over for our next question. Our next question comes from Annabelle . Your line is open.
spk10: Hi. Thanks for taking my question. So I realize I'm possibly putting the cart before the horse, but, you know, you studied GA in a range of disease severities. So how do you envision approaching this market now? It's clear from the data that the earlier the better, but clearly the most desperate are the patients at risk of losing sight and maybe getting relief benefit. So how are you initially going to be targeting this market as you enter the market?
spk22: I had a hard time hearing you once again. Sorry, Annabelle, I had a hard time hearing you. But Tim, who has better hearing than me, just clarified it for me. I think, again, one of the very exciting parts of our data set is that every other month, with half the number of injections, seems to give you close to probably 90% of the benefit in terms of slowing down the progression of geographic atrophy. So that fits very nicely with the product profile. But I think there's many product profiles, but two that stand out as being particularly attractive. One is you have a patient who has lost all vision in one eye and wants to save as much vision as possible in the fellow eye. Those are patients that probably you're going to want to treat as aggressively as possible, maybe with monthly dosing. But then the other one, the one that you alluded to, is you're a newly diagnosed patient, maybe in your first eye, you have an extra fovea lesion, the fovea is not affected, it's still small, and you're going to want to make that investment in getting the most benefits over a long period of time. And you're going to treat that patient with every two months dosing. And again, there is something there that we will continue to evaluate that we spoke about at the 18-month time point, which is that with every six-month segment, we saw that the reduction in the lesion growth became better, not linearly, but essentially the efficacy profile of the drug seemed to improve over time. And we're going to see that's not a requirement for approval, of course, but it is something that is very exciting when you think about treatments not for two, but five or ten years, especially for those early lesions. So we're going to find out what happens between month 18 and 24, but if that trend from the first three segments continues, that's something very exciting that I think we can then look forward to. Extra fovea lesions early on, newly diagnosed, and making a long-term investment with every other month dosing we believe is very important.
spk10: Okay. And if I could ask a follow-up. So a lot of the payloads we've talked to are looking for continued improvement over time and maybe separation of slopes. I know that you've shown the segment data every six months. But as far as expectations for 24 months, I guess you've somewhat downplayed what we might be able to see at 24 months. But if there's no further separation, do you think physicians will be motivated to continue to treat long-term? Is this something that we have an idea of? Is it just they're looking at sustainability or do they really want continued separation?
spk22: No, thank you, Annabelle. I think, look, if you continue to stay photoreceptor cells the way we believe you will, right, even if that is a linear saving, So if you stay around that 20% or even a little bit below that for a reduction in the growth of geographic atrophy based on the research that we did with the Red Bull community, that is sufficient. Should we get an increased effect over time, that would, of course, be very exciting and something that we can then explore at that point in time. But it's not, we believe, a requirement for adoption of this drug.
spk14: Great. Thank you.
spk19: One moment for our next question. Our next question comes from Joseph Stringer with Needham. Your line is open.
spk12: Hi, this is Ben Ricard on for Joey Stringer. Thanks for taking our question. Just a quick one. You kind of mentioned a little bit about the Impaveli payer mix. I think I heard around 25% Medicare, but just the overall payer mix, would you still characterize that as relatively stable around 50-50? or do you expect that trend to continue or change? Thanks.
spk22: Thank you, Iga. I'm going to hand that over to Adam.
spk09: Yes, so, yes, the majority of Empire Valley payer is obviously commercial, and as we said before, 25% is the Medicare population. I expect that to continue.
spk19: Great. Thank you very much. One more before our next question. Our next question comes from Douglas with H.P. Wainwright. Your line is open.
spk02: Hi, good afternoon. Thanks for taking the questions and congrats on the progress. Just maybe as a follow-up, you made the comment about, you know, a lot of trying to start patients early, especially with every other month dosing. I'm just curious, how do you think about providing guidance to clinicians about when the time might be appropriate to switch a patient from every other month dosing
spk22: to monthly dose thanks yeah thank you so much doc for that question so i think look um there is there is a dose response right but that dose response is not like you get twice the benefit from doing the monthly injections from what you get from every other month right so um but to your point if you are a patient who has foveal encroachments which means that you are now at risk for losing central vision and especially if you are already blind or have lost vision in the other eye that is a strong motivator to extract as much efficacy as you can. So it's something that we will continue to evaluate over time. And again, every other month for us is something that is very important competitively as well. I mean, again, to kind of reiterate, we have the first mover advantage. We have every other month dosing. We have data up to 18 months included in the file. And then we have patients with foveal as well as extra foveal lesions that are included in this profile. So it is something that we believe covers all populations that have this disease, whether it's early, late, whether it's foveal, extra foveal, and where we believe over the long run you can make a big difference in terms of saving photoreceptor cells.
spk02: And just as a follow-up, I'm just curious, in the conversations with KOLs, do they appreciate how much bang for your buck you get from every other month dosing?
spk22: Yes, and it is something that we will continue to work hard on because we think that up to this point, quite frankly, it has all been around what does the safety profile look like, does the drug work or not. I think, you know, we've clearly shown over time that it does work and that it works well, that it may potentially work better the longer you treat, and that with every other month dosing you're close to probably in the range of 90% of the efficacy profile of monthly without the number of injections. That's not a part of the message that we focused on, but something that we will focus on a lot in the months and years to come. Okay, great. Thank you very much.
spk19: Thank you. And I'm not showing any further questions at this time. I'll turn the call back over to Cedric for any remarks.
spk22: Thank you so much.
spk19: I'm not sure, did you hear that, for any remarks, Cedric?
spk22: My closing remarks are not opening, so I'm closing. just want to thank all of you for joining we are really excited about the progress that we have made and what's ahead for us in september we will report the 24-month data and we will be around later today and tomorrow should you have any additional thank you again for joining us today and have a day and have a wonderful rest of the week well ladies and gentlemen let's conclude today's presentation you may now disconnect and have a wonderful
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