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spk07: Good day, and thank you for standing by. Welcome to Appella's fourth quarter and full year 2021 financial results conference call. At this time, all participants are on a listen-only mode. After the speaker's presentation, there'll be a question and answer session. To ask a question during the session, you'll need to press star one on your telephone. Please be advised that today's conference is being recorded. If you require any further assistance, please press star zero. I would now like to hand the conference over to Meredith Kaya, Senior Vice President of Investor Relations and Strategic Finance. Please go ahead.
spk04: Good afternoon, and thank you for joining us to discuss Appellus' fourth quarter and year-end 2021 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'd 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'll turn the call over to Cedric.
spk17: Thank you all for joining us today. 2021 was a remarkable year for Appelis. We received our first MDA approval for MPAveli delivered an exceptional initial launch, reported top-line results from our Derby and Oaks studies positioning us to potentially receive our second FDA approval, and advanced our broader pipeline. Or simply said, we strengthened our position as a global leader in complement. Let me start with Empaveli. In May of last year, Empaveli was approved by the FDA for the treatment of adults with paroxysmal nocturnal hemoglobinuria, or PNH. This approval marked the transition from us being an R&D-focused company with a passion to develop transformative therapies to now also being a commercial stage company delivering the first ever targeted C3 therapy to patients. And Paveri is well-positioned to elevate the standard of care, and I am excited by the progress we are making so far with the launch. Physician feedback is strong, patients are reporting significant improvements, compliance is high, and we are seeing continued positive recognition by payers. Globally, we and our partner Sobi were also thrilled to see additional approvals over these past few months, including in the European Union. In ophthalmology, the phase three results from Derby and Oaks in geographic atrophy, or GA, were a critical step in our efforts to bring the first ever treatment for GA to patients. Since reporting top line results last September, the team has been engaging closely with the retinal community through medical meetings, one-on-one discussions, and many other forums. We received positive FDA feedback last fall and recently completed the pre-NDA meeting, the final step in the run-up to our submission. More than ever, we believe Pexita CoPlan represents a potential breakthrough for the 5 million patients globally who are living with GA, a relentless disease that is a leading cause of blindness worldwide. We also made progress in advancing our broader pipeline, including our late-stage programs with systemic Pexita CoPlan and our three preclinical programs. Let me now spend a moment on our key priorities for 2022. First, as I mentioned, we are focused on bringing texetacoplan to the market as the first-ever therapy for patients with GA. GA can best be described as a forest fire raging through your retina, which is a continuous process with irreversible retinal cell death. Once these cells are gone, you start going blind, and there are currently no approved treatments. We believe that with Bexia Taculplan, we have an opportunity to slow this process and preserve patients' vision for longer. We are actively preparing our NDA and are on track to submit it to the FDA in the second quarter. We will include 18-month safety and efficacy data from Derby and Oaks in our NDA and and plan to share these data publicly in March. In parallel, we are beginning the pre-submission discussions with European regulators. Our initial market research has been quite encouraging, and as we approach a potential approval, we will continue our efforts to educate the physician and patient communities. Secondly, we aim to elevate the standard of care in PNH and further establish Empaveli as a first-line treatment. We want to ensure that all patients with PNH, regardless of their baseline hemoglobin levels, have the potential to benefit from Empaveli. Beyond PNH, we are seeking to advance Empaveli as a transformative therapy for rare, complement-driven diseases. Together with SOBI, we plan to have four late-stage programs underway this year. Collectively, these opportunities could address the needs of as many as 35,000 patients per year, significantly expanding the opportunity for mPaVirine. Third, we want to advance systemic pexetacoplan as a novel approach to enabling adeno-associated viruses, or AAVs, for gene therapies by controlling the many issues that are associated with these therapies. By targeting C3, We believe that we may be able to see benefits such as increasing safety and tolerability, decreasing the dose needed, and allowing for dosing in patients with preexisting antibodies. In collaboration with our research partners, we look forward to sharing preclinical data in the first half of this year. And finally, we are continuing to advance our pipeline and plan to expand our clinical portfolio with the submission of an IND for APL 1030 our first-in-class brain-active C3 inhibitor in the second half of this year. We also are continuing to progress additional programs, including APL2006 and our siRNA plus mPavetti program towards the clinic over the next 18 months. We look forward to reporting on our progress across these four strategic priorities over the course of 2022. By the end of this year, we could have two commercial products, a robust pipeline encompassing multiple late-stage rare disease programs, and additional preclinical programs heading into the clinic, further cementing our position as a global leader in complement. I am amazed by the extraordinary science that has been pioneered by the team here at Apelis. 2021 was an incredible year, and we look forward to building on our momentum in 2022. And let me now turn the call over to Adam for a commercial update. Adam?
spk16: Thank you, Cedric. As Cedric mentioned, Empaveli's commercial results in PNH continue to be strong since our launch last May. As a reminder, in the U.S., approximately 1,500 PNH patients are currently treated with C5 inhibitors, and another 150 are newly diagnosed each year. As expected, demand was initially generated by patients on C5 inhibitors who are highly transfusion dependent. However, we are also seeing patients with hemoglobin levels near normal that have also experienced the benefits of Empaveli. Patients from this latter group can still suffer from symptoms such as jaundice and fatigue, which result in prolonged morbidity. and the feedback from those on Empavelli has been very positive. With a clinical profile demonstrating superiority in raising hemoglobin levels as compared to C5 inhibition and in line with our key priorities for 2022, we aim to further establish Empavelli as a first-line treatment for patients. Since our launch in May through the end of December, we saw continued positive momentum across several key metrics, including over 125 start forms in total received since launch. We continue to see the vast majority of Emper Valley patient starts coming from C5 inhibitor patient switches, with over 75% of these switches coming from Altamiris. We also hit our 2021 goal of having 90% of our top payers place Empaveli in a positive formulary position. As we've described, we initially focused on the top 20 payers covering approximately 85% of all US PNH prescriptions. Several large payers have placed Empaveli as exclusive for all treatment naive patients or as a preferred agent for PNH. As we continue to secure broader payer coverage over time, we expect growth to net levels to net out in the low to mid teens percentage range, consistent with other rare disease drugs. And lastly, we are seeing high patient compliance rates, which is a testament to the benefits of Emper Valley and how much better patients feel when their disease is well controlled. We do anticipate that this will come down slightly over time, but these initial compliance levels are very encouraging. We are optimistic about the continued momentum in 2022 and beyond. We are still very much in the early stages of the launch as we continue to educate physicians, secure additional payer coverage, and hopefully benefit more and more patients. Like many other pharma companies, in-person engagement slowed in January due to the spread of the Omicron variant. We continue to utilize a variety of digital technologies to continue to reach HCPs virtually, but there is a strong correlation between in-person interactions and uptake. We expect this impact will be brief and that we will maintain our strong growth trajectory over the course of this year. Turning to our global efforts, EU launch activities are also progressing with our partners, SOBI. As a reminder, EU approval was received in December 2021 under the brand name ASPA Valley. And SOBI's initial commercial launch in ex-US markets is expected this quarter. We were also pleased to see additional approvals in Australia and Saudi Arabia, key milestones in our collective goal of bringing EMPA Valley to patients around the world. 2022 is also going to be a pivotal year for Pexeta-Coplin in GA. and a potential game changer for many of the 5 million patients suffering from GA globally. With the NDA submission on track, our commercial team is preparing to launch what would be the first ever therapy for GA. Near-term initiatives prior to approval will focus on disease state education, as well as KOL and payer engagement activities. Market research and general feedback from retina specialists continue to reinforce our belief in Pegstetter-Coplin's blockbuster potential. This feedback supports the huge unmet need in GA and the paradigm shift that Pegstetter-Coplin could drive for patients. We look forward to providing more detail on our commercial plans as we prepare for a potential launch. I will now turn the call over to Fede to review our clinical developments. Fede?
spk15: Thank you, Adam. A top priority for APELIS is our NDA submission for GA, and we are on pace to submit the NDA in the second quarter. We believe we have a robust data package with data from 1,500 patients across three trials, Derby, Oaks, and Philly. We were pleased to receive feedback from the FDA last fall, stating that they do not make distinction between phases, provided the clinical trial is adequate and well-controlled. and that all three trials appear to be adequate and well-controlled. The totality of the data package underscores the potential of pexetocoplin in this indication. We think about the approval process in three important components, biological activity, treatment effect, and safety. First, biological activity. In all three trials, pexetocoplin slowed the retinal cell death that typically occurs in GA. This was shown by the rate of reduction in GA lesion growth that was observed in the primary endpoint. This effect was then confirmed in the fellow analysis, assessing the rate of reduction in patients who have bilateral GA. Second, treatment effect. The magnitude of effect was further evaluated in a post hoc analysis adjusting for baseline imbalances known to be associated with lesion growth. There is a wide range of variability in the characteristics of GA across the patient population. This analysis helps to minimize the variability and again, in all three trials, show a clinically meaningful treatment effect. And lastly, safety. Derby and Oaks demonstrated a favorable safety profile building on the safety profile that was observed in Philly. There does seem to be some confusion around how exudations were reported in our studies, and we want to take this opportunity to clear this up. The same criteria for reporting exudations were used across Philly, Derby, and Oaks. As Cedric mentioned, the NDA will also include 18-month data from Derby and Oaks. including the rate of reduction in GA lesion growth extended out into year two, and the overall safety profile. Given the need in this indication, we plan to request priority review, which if granted, will allow for a six-month review cycle. This could set the stage for a potential approval by the end of this year. We look forward to working with the FDA to hopefully bring this drug to as many patients as possible as quickly as possible. Before I move to Empavelli, I would like to briefly comment on our efforts in intermediate MD. We had a productive discussion with the FDA. Based on their feedback on expected endpoints, we believe that pivotal studies in intermediate MD should be sizable and lengthy, which would require significant investment. As a result, we have de-prioritized development of this program for now and will re-evaluate over time. This does not minimize our view of the admin need in this disease or the benefit of texetacoplan as a potential treatment. Another key objective for 2022 is delivering in the broad platform potential of Empaveli to advance our world disease franchise. To that end, Our development strategy includes four late-stage studies in multiple complement-driven diseases. For our ongoing LS study, we continue to expect to complete enrollment in the first half of 2022. Additionally, our partner, SAVI, commented in the recent earnings report that they dosed the first patient in the Phase II study in hematopoietic stem cell transplantation-associated thrombotic microangiopathy, or HSCT-TMA, and that they expect to initiate the Phase III study in colaglutin indices, or CAD, in the first half of this year. We're also actively screening patients in anticipation of dosing our first patient in the Phase III study in immune-complex membranoproliferative glomerulonephritis, or ICMPGN, and C3 glomerulopathy, or C3G. We look forward to sharing our progress across these programs. Let me now turn the call over to Tim for a review of the financials. Tim?
spk13: Thank you, Fede. Since we issued a press release earlier today with the full financial results, I will just focus on the highlights for the full year 2021. Total revenue for 2021 was $66.6 million, which consisted of $15.1 million in Empaveli net product revenue in the U.S., a strong start for the franchise. We also recorded a $50 million milestone payment from SOBI in connection with the first regulatory approval and reimbursement approval in Europe. With EU approval granted last December, we view the likelihood of achieving the milestone as high and therefore recorded the revenue in the fourth quarter in accordance with U.S. GAAP. We continue to expect to achieve this milestone and receive the cash in the first half of 2022. R&D expenses were $426 million, which included the $50 million upfront payment associated with the BEAM collaboration. We also accrued an additional $25 million on our P&L in 2021 associated with the payment due on the one-year anniversary of the BEAM collaboration that we view as likely to occur in the coming months. G&A expenses were $177 million, and we reported a net loss of $746 million for the year. As of December 31st, 2021, Appellus had approximately $700 million in cash, cash equivalents, and short-term marketable securities. This reflects net proceeds of $380 million from our recent offering in November, which we believe will provide us with the resources to execute our strategy into the second quarter of 2023. Looking ahead to 2022, with an approved product in Empevelli, a robust pipeline, and a potential upcoming blockbuster in GA, we are confident in the Palace's financial future. I will now turn the call back over to Cedric for closing remarks. Cedric.
spk17: Thank you, Tim. We have made excellent progress and look forward to an exciting 2022. Let me close with a brief recap of our upcoming milestones. In the first quarter, we are starting our pre-submission discussions with European regulators for GA. And for Aspavedi, we expect the initial ex-US PNH launches by our partner, SOE. In the second quarter, we plan to submit our NDA and geographic atrophy to the US FDA and publish our preclinical data on AAVs administered with C3 inhibition. Over the course of the first half, we expect to complete the enrollment in our Phase II study in ALS, initiate the Phase III study in ICMPGN and C3G, and SOVI plans to initiate the Phase III study in CAD. In the third quarter, we plan to report the 24-month Derby and Oaks update. And in the fourth quarter, should we receive priority review, we expect to have an approval decision for GA in the U.S. In the second half of this year, we also expect the MAA submission in the European Union for GA and to submit our IMD for APL 1030. We look forward to updating you on these efforts. Let us now open the call for questions. Operator?
spk07: Thank you. As a reminder, to ask a question, you'll need to press star 1 on your telephone. To withdraw your question, please press the pound key. Please stand by while we compile the Q&A roster. Our first question comes from Madhu Kumar with Goldman Sachs. Your line is open.
spk09: Yeah, thanks for taking our questions, everybody. So let's start with CAD. So I guess kind of how are you thinking about pivotal trial design with your collaborator, SOBI, given the recent approval of the Sanofi drugs, the Timlamab, and the condition?
spk17: Thank you so much, Manu, for that question. So SOBI has been working hard in collaboration with us to prepare for this trial in colic glutenin disease. So Timlimab, as you know, is a drug that is given intravenously every two weeks. So there's an important, I think, you know, advantage to treating, to self-administering the drug at home twice per week. As we have always said from an efficacy perspective, we will have to see if there is really a benefit to be gained, but it is really the convenience of at-home dosing. That trial is going to start in the very near future. And, you know, right now it is a trial that will kind of follow the conventional registration endpoints in colic gluten disease, and we're not yet guiding on when it will read out.
spk09: Okay. Moving over to GA. So you guys have announced you guys are going to have 18-month data in March, and you're going to use that as part of the filing package. How much of that data is kind of, already in hand, and, like, what are the kind of considerations people should have when thinking about that data relative to the results put out in September of last year?
spk17: Yeah, thank you, Madhu. So in September, when we, after the primary endpoint readout, when we engaged in our discussions with the regulators, we proposed to include the data beyond 12 months on the lesion size growth, you know, to really get a full sense of what the effect size of the drug would be over time. And we agreed to include, since it would not affect our timelines for submission, we agreed to include all of the data available up to 18 months, both on efficacy as well as on safety, and with efficacy in this case, of course, indicative of lesion growth, and whatever we have available beyond 18 months as well.
spk09: Okay, and one last question on the Empaveli launch. I want to kind of come back to something Adam said about patients who are coming on to Epivelli despite having normal hemoglobin, how should we think about the kind of distribution of those patients and where you think there's a longer-term opportunity for those patients who don't have, say, low hemoglobin levels but, as you mentioned, could have other kind of complications of PNH that would switch over onto Epivelli as compared to the existing therapies?
spk17: Yeah, so patients with normal hemoglobin levels are on average represent approximately a third of the patients who are on treatment with C5 inhibitors. But I think the really important point about what we aim to achieve in PNH is to elevate the standard of care, not for patients who are transfusion dependent or who have poor hemoglobin levels, but in all patients with PNH. Patients with normal hemoglobin levels in PNH get to those normal hemoglobin levels because they have very good bone marrow and produce typically a very large amount of red blood cells. But these red blood cells also, in an unusual way, die in this process of extravascular hemolysis. That can lead to jaundice, where patients have an ashen appearance. It leads to reticulocytosis, where a maximum amount of red blood cells have to be made in the bone marrow. And in short, this disease is not well controlled more broadly when extravascular hemolysis is not addressed. Adam, I don't know if you want to add something to that.
spk16: Yeah, well said, Cedric. So yeah, we're seeing a much wider use of Empaveli as we expected as we're getting through the stages of the launch, right? So we expected to have the hardest to treat patients first, those who are heavily dependent on transfusions. Now we're seeing those with high hemoglobin levels, hemoglobin levels around 10, for example. And we're seeing really and hearing really positive results of those patients. We're also hearing treatment naive patients are starting on Ember Valley too. So it's where we should be in this phase of the launch, right? The hardest to treat patients, physicians have got experience, and now they're broadening their experience to a wider population. So the team's working incredibly hard to remind people that this is a first-line product, and we believe we can truly elevate the standard of care, and we're seeing that transition within the market. Okay, great. Thanks very much.
spk17: Thank you, Madhu.
spk07: Thank you. Our next question comes from Don Miller with Evercore ISI. Your line is now open.
spk14: Thanks for taking my question, guys. I guess while we're on the subject of longer-term data for GA, what functional data should we expect to be included in the NDA, and has the agency made any specific requests on that front, or is there any specific guidance on that? I think we all expect The imaging data to be front and center was the primary endpoint, but what's the role of functional data from a doc perspective in your market research and outreach versus imaging alone when they talk about drivers of prescribing?
spk17: Thank you so much, John. So the formal analysis on the functional endpoints will happen at 24 months, the way it has always been planned. And then the way physicians look at it, I think most retina docs understand very well that a reduction in the growth rate of geographic atrophy, as measured by autofluorescence, is reflective of a loss of photoreceptor cells. So if you lose photoreceptor cells, you lose vision. So that clear connection between living cells and being able to see is also the really key reason why the FDA found this endpoint to be acceptable as the primary endpoint, of course.
spk14: Great. Makes sense. I guess on some of the rare disease trials that we're expecting to get started, it seems like these have been a little bit slower to get off the ground than you were suggesting last year. Obviously, we haven't seen some of those Phase III studies start already. I think we were expecting some of them in Q4. So how should we think about timelines for really the bulk of the Phase III studies that haven't started yet, How long is it likely to take to get those up and running, and what are your expectations for readouts there?
spk17: Yeah, thank you, Jean, for the question. Yeah, so with, you know, I think reflective of the broader industry, getting studies started these days can take a little bit longer than expected. We also, of course, have to coordinate with our partner, Sobi. We're very happy with the designs that came together and with the regulatory feedback that led to those designs. and you should generally expect all three of these new trials to start in the first half of this year, many of them now imminent in the very near future.
spk14: Okay, thanks very much. And as we think about P&H launch, I guess, the last one, I know you guys told us that you expect gross net to even out to the low to mid-teens sort of standard levels there, but But at this point, given that your commercial patient mix has been reasonably good in the launch, what's your expectation for the remainder of the trend there? How much longer until we hit equilibrium on gross to net, and what are we waiting for on the rest of your commercial transition?
spk17: Thank you, John. I will hand that over to Adam and Tim.
spk16: Yes, thanks, John, for the question. Yes, so we still have some work to do with some payers. We had a great start to our launch last year and hit all of our targets with payers. So now we have some more targets with payers that we're executing in this phase of the launch. So as we start to continue to try and get as good an access as is possible with all of the payers that cover P&H lives, that will have potentially an impact on growth today.
spk14: Okay, thanks.
spk07: Thank you. Our next question comes from Anupam Rama. Your line is now open with JP Morgan.
spk11: Hey, guys. Thanks so much for taking the question. Just a quick question on the 24-month data. I don't think this is the case, but just to confirm that there are no plans to submit the 24-month data to the FDA, or rather you might do it as a supplement at a later point. Thanks so much.
spk17: Thank you so much, Anupam. Yes, we do not have plans to create an amendment to include the 24-month data. It will, of course, be available to us around that period in time, but we believe that we have everything available, and the FDA agrees to do our submission in the second quarter as well.
spk11: Thanks so much. You're welcome.
spk07: Thank you. Our next question comes from Laila Youssef with Cowen. Your line is now open.
spk10: Hi, this is Lila on for Phil. Thank you for taking the question. This may be on the potential commercial prep in GA. Can you maybe talk a little bit about the progress with hiring a potential sales force? And in terms of your near-term initiatives, have you already gone through and identified maybe key positions you plan to target? Thank you.
spk17: Thank you, Lila. I will hand that one over to Adam as well.
spk16: Yep, thank you, Lila. So yeah, I'm very happy with the progress for hiring towards the GA launch. So we've hired all of the leadership positions in medical affairs, sales, marketing, and market access within the U.S., and also the leadership positions outside of the U.S. in our EU office in Zug in Switzerland. We've also set up affiliates in Germany and Australia as well. So we're progressing really well. We've identified the size and the scale of the sales force. You know, a good benchmark for everyone is the way MD products are We've used them regularly to make sure that we've got the right level of approach for when we potentially come to the market. And we're probably going to target in the U.S. about 3,000 retina physicians. A much smaller subset of those do the majority of the wet AMD administration. But you can see, right, it's not a huge build. It's well within Appellus' capabilities. So we are ready to go and we'll be very thoughtful as we start to expand and hire the sales force. We're very excited to progress towards that.
spk10: Very helpful. Thank you.
spk16: Thank you.
spk07: Our next question comes from Stephen Seedhouse with Raymond James. Your line is open.
spk01: Hi. Thanks for taking the question. Cedric, you mentioned just in response to an earlier question about including whatever data is available beyond 18 months as well. I was just hoping you could clarify what you meant there if you were just speaking about lesion growth data or something else. Yes, thank you, Stephen.
spk17: Just to clarify, I'm talking about lesion growth data, correct?
spk01: Okay. And is the FDA, in your dialogue with them about this 18-month analysis, interested in the slope of the data or just a point estimate at 18 months?
spk17: The FDA is interested in the totality of the data, right? So we've had discussions with them around the MRM-transformed data around slopes, around fallow eye analysis. I mean, all of these things we believe are relevant, and I think this is a division that takes all of the data into account in its evaluation.
spk01: Okay, and maybe two just real quick last ones, or I guess the second one might not be so quick, but your current view in your dialogue with the FDA of an ADCOM. I know previously you had said you did not expect one, but I'm just curious about your updated view. And then the fellow I analysis that you just mentioned, there's plenty of debate in the investment community about this analysis, so it seems like you've had dialogue with the FDA about a fellow I comparison and why it may be valid supportive efficacy assessment. Could you just expand on that? Thanks so much. Yeah, thanks so much, Steve.
spk17: So the outcome, of course, is not our decision, right? We will be ready to have one, and we will see what the FDA decides to do. On the fellow eye analysis, as I mentioned, it is something that is, we believe, very important and confirmatory of the biological activity for the drug. It is something that we have discussed with the FDA. And, you know, I would say that what stands out probably the most in Philly, Derby, and Oaks are the sham control groups, right, where you clearly see how, and this was well described in the past by investigators like Janet Sennins, where the study eye and the untreated fellow eye progress at virtually identical rates, with, if anything, a little bit of a faster progression typically in the study eye, which is the worst-seeing eye. So I think it's a really impressive control, and in all three studies we see a consistent dose-response effect compared to the fellow eye, as opposed to the sham control.
spk16: Thanks for taking the questions. You're welcome.
spk07: Thank you. Our next question comes from Colleen Cussie with VARED. Your line is open.
spk06: Hi, good afternoon. Thanks so much for taking our questions. So have you gotten any feedback from regulators, or do you have any thoughts on how regulators may evaluate the every other month versus the monthly dosing arms?
spk17: So our plan to submit, Colleen, is the complete data package for monthly as well as for every other month. So, you know, that has been discussed, and that is what will be part of the package.
spk06: Okay, great. Thank you. And then, so following up on PNH, you're quite impressive that you've been able to get even exclusive reimbursement for Ampavelli versus C5 inhibitors. Do you see that continuing to grow still, or how do you think about the favorable reimbursement that you've been able to get in P&H?
spk17: Thank you for that question. Adam, would you like to comment?
spk16: Yeah, sure. Thanks, Colleen. So, yeah, I'm actually very proud of the team. We've done some great work with all of the payers. It does help that we have some great data that, you know, we can talk to the payers about, particularly around transfusions and hemoglobin, et cetera. So, We've managed to have some really robust scientific conversations that have got us to a very positive position with many, many payers. We want to continue to have those discussions over the next couple of months and make sure that every patient that wants to get access to Empaveli can get access to Empaveli. And so that's our plan as we continue. So, yeah, team's done a great job. We're not over yet. We want to continue to keep pushing.
spk06: Great.
spk07: Thank you so much for taking our questions. Thank you. Our next question comes from Alethea Young with Cantor Fitzgerald. Your line is open.
spk03: Hi. Good afternoon, and thank you for taking our questions. This is Nanon for Alethea. Maybe two from us. For GA, we know that PEG is ahead in clinical development, but how are you guys seeing the competitive landscape shaping up in GA if some of the competitors have positive data? And the second, just if you could share if there's been any ongoing COVID impacts across the business. Thanks.
spk17: Thank you so much, Adithya. So just for the COVID question, was that related to geographic atrophy?
spk07: Just across the business overall.
spk17: Across, yeah. Okay. Well, so first of all, as it relates to geographic atrophy, of course, we will have to see what happens with the data this summer. Just a quick reminder across that backdrop how we plan to submit our data package, because we believe that every single component of that submission is important. First of all, of course, there is the safety, which was better than I think most people expected. Number two, there is the biological activity, with two studies having shown a positive primary endpoint out of the three, and the fellow eye analysis to confirm that biological activity The third piece is then what is the real effect size? Because across these three studies, at least at one year, we see between 12 and 29%. And the reason why these results can be divergent is because the baseline characteristics of these patients can be very different and cannot be controlled for in these studies because there are too many. So what you can do is afterwards do an analysis where you model these baseline differences between active and sham groups and where you see a clear effect that is north of 20%. And then the last piece will be, you know, again, what will that effect look like beyond 12 months? You know, is this a durable effect in patients? What does this mean in the long term for these patients? Also very important, of course, in our submission is the every other month dosing on which we had a statistically significant result both in Philly as well as in Oaks, as when something that we believe is a really important advantage for physicians and for patients, especially in patients that are early on in the disease and those patients that typically present for the first time with extra fovea lesions. Being able to dose every two months instead of monthly is a very important advantage. So that's as it relates to geographic atrophy. As it relates to COVID, You know, the impact on the trials has been limited in geographic atrophy. We used to speak about that a lot, right? But we believe that the impact on the studies has been minimal. As it relates to the additional registrational studies that we have ongoing, the only one, of course, in this case that is really important is the ALS study. And there we have not really seen an impact either. So, Federico, I don't know if you would like to add something to that for the COVID impacts on clinical trials.
spk15: No, I think you're right. Most of the impacts that we have seen across the board in pharma is on the initiations of new studies. Omicron played a bit of a role in there. But other than that, no major effects of COVID, I would say.
spk07: Thank you. Thank you so much. Thank you. Our next question comes from Tazeen Ahmad with Bank of America. Your line is open.
spk05: Hi, good afternoon. Thanks for taking my question. And I'm sorry, I did join this call a few minutes late. So if you've already answered this, I'm sorry for asking it a second time. But just in terms of your expectations for the time to review, is it possible that you could get a regular review period, not an accelerated path, just because It does seem that in our experiences monitoring other companies during COVID at least, it seems like FDA is taking a little bit longer. They are issuing more, you know, Paducah extensions, for example. So, you know, based on your most recent discussion with the agency, have they provided any color on your review period, what that would be? And if you do expect an adcom, do you think that one could happen you know, if you, you know, got a more shorter review period, a priority review. Thanks.
spk17: Thank you so much, Desmond. So we have not received any indication so far that, you know, we would have a longer review time than usual. So our discussions with regulators have all been positive. We, of course, cannot predict whether we will have priority review time. We are hopeful that we will, based on precedent and based on the unmet needs that exist in this disease, of course. And then as it relates to the outcome, it kind of really goes back to the first question as well, where we will have to see what comes out of the acceptance. But we are optimistic that we will receive priority review, and that should there be an outcome, that the feedback from physicians will be positive.
spk07: Okay, thank you.
spk17: You're welcome.
spk07: Thank you. Our next question comes from Nigal Nachimovitz with Citi. Your line is open.
spk12: Great. Thanks for the questions. Cedric, regarding the 18-month look for Derby and Oaks, so obviously you've seen a very appreciable and steadily increasing separation of lesion growth curves through 12 months, almost like a wedge growing between pexetococcal and the sham. So my question is, do you believe you need to see a continuing separation of the lesion growth curves between pegcidib, Copeland, and sham at the 18-month point to support approval, or as long as the curves stay separated and don't converge at the later time points, that will be sufficient for a favorable efficacy claim?
spk17: Thank you, guys. So we have not received specific feedback on that particular expectation that you're talking about. but we are looking for a continued effect over time. Should there be a separation, of course, that would be an extraordinary outcome.
spk12: Okay, great. And then just one follow-up regarding the pre-NDA meeting. I'm just wondering if the FDA weighed in at all regarding some of the changes in formulation that have occurred with pig-sidic copeline over the years, i.e., from the lyophilized form in Philly to the pre-filled vial in Derby and Oaks, where you had a slight excipient change, and then finally, I believe after approval and launch, you will introduce a pre-filled syringe.
spk17: Correct. So just to be clear, what we did in the phase three clinical trial was a pre-filled vial, and we will also launch with a pre-filled vial. In the future, you know, we will in all likelihood introduce a pre-filled syringe, but that takes several years of development. But, you know, the key thing here is, you know, this was not a pre-NDA meeting, but Immediately after we had the data in September, we thought it was important to understand the regulatory view on the Philly trial. And what we did is we sent to the FDA the three trials in parallel, explaining what the similarities and the differences were, what the quality of the studies was, how they were run, et cetera, with a specific question what the regulatory view was on the trials. And the answer that we received from the FDA was described in the second paragraph of the press release that we released early on in November at the time of the American Academy of Ophthalmology. Thank you. You're welcome.
spk07: Thank you. Our next question comes from Ellie Merrill with UBS. Your line is open.
spk02: Hey, guys. Thanks so much for the question. Just a logistical clarification question. In terms of the stats around the 18-month analysis, could you just remind us of those? And I guess in the discussions with the FDA, any discussion around any additional analyses at 18 months or any kind of, you know, things that made learning from, say, the fellow eye data, say, in terms of this 18-month analysis? And then just also just a clarification question, I guess, is the NDA filing contingent on the data seen at 18 months or is this sort of just you know, additional color and data that could potentially get in the label. Thanks.
spk17: Thank you. So the formal analysis will happen at the 24-month time point. So we will, of course, run stats at 18 months, but it will be descriptive in nature. The contingent piece is we went to the FDA and we proposed to include that because we realized that we had an opportunity to do that with the timing that we had in mind and include it in our complete NDA submission without a significant delay. So that was something that we saw as an important opportunity to provide a more complete data package and all possible data as it relates to the lesion size growth. So as it relates to the type of data that we will include, it is the lesion size growth and the safety.
spk07: Got it. That's helpful. Thanks.
spk17: You're welcome.
spk07: Thank you. As a reminder, to ask a question, you'll need to press star 1 on your telephone. Our next question comes from Joseph Stringer with Needham & Company. Your line is open.
spk08: Hi, everyone. Thanks so much for taking our question. Just given you're going to be starting a phase 3 trial in ICMPGN and C3G, just can you remind us of the market opportunity in this indication and what you'd be looking for in terms of you know, a competitive profile for Pexida-Copeland in this indication. Thank you.
spk17: Thank you, Joey. So we view C3G and ICMP-GN as very important next indications for Empaveli and Aspaveli. You know, we had a robust and very impressive proof-of-concept study that was run in C3G, as you may recall. In terms of the market opportunity, the market opportunity for each of C3G and ICMP Gen should probably be viewed in the range of what P&H represented. This is, of course, an unmet need for which there are currently no approved therapies, and based on our data, we believe that we have the possibility of having a best-in-class profile.
spk16: Great. Thanks for taking our question. You're welcome.
spk07: Thank you. And I'm currently showing no further questions at this time. I'd like to hand the conference back to Mr. Cedric Francois for final remarks.
spk17: Thank you so much, Norma. In closing, thank you all for joining us today. We look forward to keeping you updated on our progress in the months ahead. We are around later today and tomorrow. And if you have any additional questions, feel free to reach out to Meredith. Thank you again for joining us today and have a wonderful rest of the week.
spk07: Ladies and gentlemen, this concludes today's conference call. You may now disconnect.
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