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spk08: Hello, and thank you for standing by. Welcome to the Q3 2022 Appellus Pharmaceuticals Earnings Conference Call. At this time, all participants are in listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, please press star 11 on your telephone, and you will hear an automated message advising your hand is raised. Please keep in mind that today's conference is being recorded. I would now like to hand the conference over to your speaker, Meredith Kaya, Senior Vice President of Investor Relations and Strategic Finance. Please go ahead.
spk19: Good afternoon, and thank you for joining us to discuss the Palace's third 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'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 details. Now, I'll turn the call over to Cedric.
spk03: Thank you, Meredith, and thank you all for joining us today. Let me start this call with what is on all of our minds right now, which is our decision to submit the 24-month efficacy data from the Phase III Derby and Oaks studies to the FDA. This submission will be considered a major amendment to the NDA, extending our review timeline by three months, with a new PDUFA expected in February 2023. Let me just state up front, since we have received so many questions about this, that this decision was ours. This was not requested by the FDA. The reason why we decided to do this is because including these efficacy data gives us the opportunity to have the best product profile at launch with minimal impact to our launch timing. Recall that they already had the 24-month safety data as part of the 120-day update. The inclusion of these additional data in the label would allow us to better educate physicians and patients with a clear message around the robust treatment effect of dexetacolpan over the full two-year period. Remember, at 24 months, both every other month and monthly treatment with dexetacolpan resulted in meaningful slowing of GA progression with increasing effects over time. Between months 18 and 24, 24% and 30% respectively, with every other month and monthly treatment. Importantly, at month 24, the data were remarkably consistent between Derby and Oaks, meaning that we can spend more time discussing the efficacy of the two studies rather than the differences between them. And we continued to see a favorable safety profile in over 1,200 patients with nearly 12,000 injections. Now let me talk about why we did this now, which we recognize appears unusual given how close we were to our original BDUFA date. At the time of our 24-month top-line readout in August, given how strong the data were, we had the discussion internally as to whether we would file a major amendment. We decided against it because we believed that it would delay the timing of our launch and the timing of our permanent J-code by three months. We also did not expect the 24-month data package to be completed before the B2FA without compromising the European filing deadlines. However, as we continued to prepare for the launch, some of these factors changed. The completion of our 24-month data package happened faster than we expected, putting us in a position to submit the data prior to our B2FA without delaying our European filing. Also, given the December holidays, changes to medical coverage at the start of the year, and finalizing the supply logistics, we had already made the decision to launch in January, which also meant that we would receive our J-code in October. The combination of these factors meant that the impact of the extended review period would only be a six weeks delay to commercial launch, with no impact on J-code timing and the best possible label. The FDA is aligned with our decision to submit these data. We understand that this came as a surprise, and we did not take this decision lightly. There is a significant unmet need in this disease, and patients are waiting for a treatment. But we also strongly believe that this is the right decision. It is the fastest way to get our 24-month data into the label and to deliver the best product profile to physicians and patients. The U.S. approval is the first step in our overall strategy to bring Pepsitacotan to GA patients around the world. We remain on track with our EU marketing authorization application and plan to submit our MAA by the end of this year. Turning now to the rest of the business, the Empaveli launch continues to progress well in its second year on the market with U.S. product sales of $17.7 million in the third quarter. Globally, our partner, Sobe, is also making progress in bringing Aspavedi to people with PNH. Beyond PNH, we continue to advance Ampavedi as a transformative therapy for other rare, complement-driven diseases, AAV-based gene therapy products, and neurodegenerative conditions. And our early-stage pipeline including both our collaboration with BEAM and our internal programs, continue to advance. And with that, I will turn it over to Adam.
spk04: Thank you, Cedric. I will start with our commercial plans for PEC Setter Copeland in GA. The team is excited by the potential of having the 24-month data in the label at launch. Physicians' perceptions of these data has been very strong, based on both recent market research and direct feedback we have been receiving as recently as last week at the Retina Society meeting. In any launch, the label is the most important document that you can have. Having the 24-month data included in the label allows us to have a more impactful conversation with the physician, broadens how they think about using pexetocoplin, and allows them to have a more meaningful conversation with their patients. With a minimal launch delay, it became clear that including these data in the application was the right decision. We have approximately 100 people across our commercial and medical teams currently engaging with retina specialists, working to build a sense of urgency around GA treatment through disease state awareness and education. We will continue this disease state education until approval. I am impressed with the talent of our expanded team who come from both large and small companies and bring significant expertise in launching new drugs within the retina. They are incredibly motivated to bring the first and only GA therapy to market. Now, let me turn to our current commercial product, Empavelli. In the third quarter, we continue to see positive trends across the key leading indicators for this patient population, including approximately 30 staff forms, 40 additional physicians receiving REM certification, high patient compliance rates, and continued strong access among the top 20 payers. This resulted in $17.7 million in U.S. net product sales for the third quarter. As mentioned on the last quarterly call, following Emper Valley's first year in the market, we have expanded our focus to the broader P&H community by further positioning Emper Valley as first-line treatment for every adult living with P&H who could benefit from it. As such, we brought the full field team together during the quarter to focus on three key areas For the second phase of our launch, we refined our target list of healthcare professionals so that we can efficiently call on prescribers who are treating the majority of P&H patients. We further evolved our partnerships with key centers, and we realigned our field structure, including the addition of new team members. We deployed the expanded field force in September, and they are now fully engaging with the P&H community. Separately, as a reminder, our SNDA with the Phase III PRINCE results and the 48-week Phase III PEGASUS data has a PDUFA date in February 2023. If approved by the FDA, this will allow us to further strengthen our promotion of Empaveli for treatment-naive patients and raise greater awareness of our long-term efficacy and safety. Let me now turn the call over to Fede.
spk22: Thanks, Adam. Good afternoon, everyone. In August, we announced our longer-term 24-month results with Pexeta Copeland and had the opportunity to share this data at multiple ophthalmology congresses this fall. The medical team has been engaging with hundreds of retin specialists over these past few months. Like Adam said, the feedback on the data has been outstanding and the possibility of having them in the label at lunch has been very well received. Results at 24 months showed two highly consistent studies demonstrating that treatment with Pexetacoplan resulted in increased effects over time with greater reductions in lesion growth from baseline to month 24. These effects were observed across both the every other month and monthly treatment arms. Then, if you look at the combined data from Derby and OX, pexetacoplin treatment showed an acceleration in the reduction in lesion growth, specifically between month 18 and 24. With reductions increasing to 24% and 30% in the average of month and monthly arms, respectively, the potential magnitude of benefit for patients could be substantial. Within the same 18 to 24-month period, pexetacopalin also appeared to be equally effective across both non-sand foveal and sub foveal lesions in both treatments on. Importantly, we continue to see a favorable safety profile consistent with what we saw at 12 and 18 months. Safety data has now been collected over two years in over 1,200 patients and nearly 12,000 injections. Turning briefly to our systemic pipeline, we are continuing to advance our rare disease franchise to deliver on the broad platform of MPaveli, which includes four later stage studies in multiple complement-driven diseases. A phase three study with Pexetacoplan in ICMPGN and C3G, and the Phase II study in HSTC-TMA are both accurately enrolling patients. In October, our partner, SOVI, announced the dosing of its first patient in the first three studies in colaglutinin disease, or CAD. And finally, we remain on track to report the top-line results from our potentially registration of Phase II study in ALS in mid-2023. Let me now turn the call over to Tim for a review of the financials.
spk15: Tim?
spk07: 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 third quarter 2022 summarized here. As you can see, total revenue was $22.1 million, which consisted of $17.7 million in EpiValley net product revenue and $4.4 million in collaboration revenue from SOBI. R&D expenses were $95.2 million, and G&A expenses were $78.4 million, and we reported a net loss of $191.3 million. As of September 30, 2022, Appellates had $708.6 million in cash, cash equivalents, and short-term marketable securities. Even with this shift in launch timing, we continue to expect our current cash balance to fund our operations into the first quarter of 2024. including the ongoing launch of EMPA Valley, the potential global launch of PEG-C to Copeland and GA, and further development of our pipeline. We remain confident in Appalachia's financial future as we continue to execute on our upcoming milestones. And with that, I will now turn the call back over to Cedric for closing remarks. Cedric?
spk03: Thank you, Tim. This is an incredibly important time for our company. Our position in the P&H market is expanding, We are close to having a second commercial product available that we believe can have a life-changing impact on people's lives, and we continue to advance a robust pipeline encompassing multiple late-stage rare disease programs as well as preclinical programs heading into the clinic. We are on track to achieving our vision of being the global leader in complementary medicine. And let us now open the call for questions. Operator?
spk08: Thank you. At this time, we will conduct the question and answer session. To ask a question, please press star 1 1 on your phone and wait for your name to be announced. Please stand by while we compile the Q&A roster. One moment, please.
spk09: Madhu Kumar of Goldman Sachs, your line is now open.
spk00: Hey, thanks for taking our question. This is Rob on for Madoo. First, what's the timeframe for submitting the 24-month data to the FDA, and how long after this submission should we expect to wait for clarity on the PDUFA data, and if an adcom is still necessary?
spk03: Thank you so much, Rob, for that question. So, in our discussions with the FDA, again, this is classified as an unsolicited submission or amendment. We agreed with the FDA that if this was submitted before the current PDUFA date, that we would get a new PDUFA date that would be sometime in the latter part of February. So, that is where we currently stand.
spk10: Okay, thank you.
spk09: One moment, please. Our next question comes from Kazim Ahmad of BAML.
spk08: Your line is open.
spk13: Hi, guys. Good afternoon. Thanks for taking my question. Cedric, I was wondering if you could share any of the feedback that you might have gotten this weekend. I know that you attended a Retina Society meeting since the press release was put out in time for you to talk about it there. Just wondering what kind of reaction you got from physicians when you mentioned that you would be applying now to have 24-month data in the label. And then, secondly, for the J-code, if your producer date does get pushed to February, when should we expect to see the permanent J-code when you launch? Thanks.
spk03: Thank you, Tati. On the feedback from the doctors, I will hand it over to Federico, who was there with me as well, but it was overwhelmingly positive. And, again, we are doing this. elaborate a little bit.
spk22: Yeah, the feedback was very positive this weekend. You know, with this disease like geographic atrophy, you know, having understanding the effects over time is highly valuable. And, you know, physicians understand that and they, you know, they really welcome our decision and the possibility of having all our data 24 months in the label to start with.
spk03: And then for your second question, Darlene, on the J code, we expect to have the J code early October.
spk13: Okay. Thank you.
spk03: Thank you.
spk09: Thank you. One moment, please. John Miller of Evercore, your line is open.
spk02: Hey, guys. Thanks for taking the question. I have a question. Have you been in labeling discussions yet with the FDA? And if so, how is that being impacted by 24-month data? And then secondly, previously you had mentioned that the agency was treating 18-month data as primary, despite the fact that the trials were designed for 12 months as primary. Do you anticipate the FDA would instead treat 24-month data as primary now? And how does that work statistically, given the trial wasn't pre-specified for the later time points?
spk03: Thank you so much, John. So our discussions on this amendments preempted the label discussions with the FDA. So to be clear about that, but again, it was a very productive back and forth interaction as it relates to the primary endpoint. So we will have to see. I mean, this is of course. Something that we that we hope based on language that we had before may indeed apply, but there's of course decision from the agency.
spk02: I understand. And separately, did the FDA ever bring up questions around the micro-parametry data in any of your earlier discussions? I ask because obviously that is another important difference between 18- and 24-month data.
spk03: Yeah, thank you, John. So we were very excited about, as you may recall, looking at the micro-parametry around the actual lesion sites where we had a signal for a functional impact of the treatment, but to be clear, the primary endpoint and every efficacy consideration with the FDA was and continues to be showing that we can anatomically reduce the growth of the lesion in these patients.
spk02: Okay, thanks so much.
spk10: Thank you, John.
spk09: Thank you. One moment, please. Anupam Rama of J.P. Morgan, your line is open.
spk06: Hey, guys. Thanks for taking the question. I thought maybe I'd throw the one PNH question that might get asked on this call. On the SNDA for epivele, just wondering what your market research suggests about how including those data from the PRINT study might change the ramp curve and the phenotype of the patient, the PNH patient that is treatment naive that might initiate therapy. Thanks so much.
spk03: Thanks, Anupam. I'm going to hand that one over to Adam.
spk04: Thanks, Anna-Pam. Yep, so obviously the team is thrilled with the progress on the Empaveli launch as we go into Phase 2. So the supplemental NDA with the Phase 3 print stage, it just allows us to have even more robust conversations with the physicians about treatment-naive patients and the benefit of switching to Empaveli. So at the moment, we have about 10% of our patients are actually treatment-naive patients. And we expect that having a much more detailed conversation in the update in the label will allow us to remind people that Emper Valley is the product of choice. So the field-based team is super excited to have that potentially in the label, and I think we'll see some really strong progress there.
spk10: Thanks so much for taking our question. Thank you, Anupam.
spk09: Thank you. One moment. Bill Nadeau of Cowan, your line is open.
spk01: Good afternoon. Thanks for taking our questions. One question that we get all the time, Cedric, is on PECC-City Compliance and the filing is whether the filing was in any way in response to a proposed label where maybe there's some elements that you didn't like. I know you just said that you weren't actually labeling negotiations, but had you seen any proposed label from the FDA? That's the first question. And then the second question, during the prepared remarks, you mentioned that the 24-month data would broaden how doctors think about using pectococcal. Can you elaborate on that? In what ways will the 24-month data change how physicians could use the drug? Thanks.
spk03: Okay, thank you. So as I mentioned earlier, so we went to the FDA with this proposed amendment. This preempted the label discussion. So we proposed that we wanted to include the full 24-month data. The FDA agreed with that. It's also important to point out that after our agreements, we actually did run the press release that we issued on the subject via the agency to make sure that we were in full alignment. And so this is the path that we chose, which we believe will be in the best interest of patients and physicians. And Adam, why don't you tell us why that is so important to you?
spk04: Yeah, absolutely. So thank you, Phil. So obviously the team and the whole of Appellus is actually excited about the 24-month data, particularly the efficacy increasing over time, more consistency between our two studies, and the robust safety. So one thing that we've done is we've tested with retina specialists in the U.S. and ex-U.S. at 12 months, at 18 months, and at 24 months. And not a surprise in our market research, the profile of the drug improved in their perception. And 24 months, we got comments from retina specialists about how they are much more comfortable about talking to a broader set of patients based on the efficacy profile of the drug and the consistency between the two studies. So I expect as we continue to do disease state education until launch, that physicians will have much easier conversations with their patients. And I would expect them to bring more patients into that discussion as a result of the strong efficacy data there. Thank you.
spk22: That's helpful. Thank you.
spk03: And just to add to this, think about it this way, right? The DERVI trial, right? The trial that just a year ago ran into the issues that we're all familiar with. And the piecewise linear analysis from about 18 to 24 of the monthly patients for the slow has a 36% slowdown in the growth and 29% for every other month. So these are just really important data for us. Again, that important effect between month 18 and 24 generates that consistency at 24 months between the two studies, and that is something that we find particularly important.
spk01: Perfect. Thanks for taking our questions.
spk09: Thank you. One moment, please. Stephen Seedhouse of Raymond James. Your line is open.
spk17: Great. Thanks for taking the questions. I just, Cedric, I wanted to go back to a comment you just made about running the press release by the agency to make sure you were in full alignment. I mean, why did you even need to give a press release last week since this was an elective decision on your part? And since, as far as we can tell, as of today, you still haven't submitted anything. The 24-month date, I mean, why not just announce that with earnings? I'm curious what prompted the press release in the first place. Yeah, thank you, Steve.
spk03: Retina Society, right? So we do this for physicians and patients, and the Retina Society is really the last important conference of the year. After this one, angiogenesis, I'd say, would be the next one, which is already in February. So we wanted to have the opportunity to really speak openly about this with the retinal community.
spk17: Got it. Okay. And then how much did competitive dynamics specifically play into this decision? So anticipating, you know, potential competitor and Iverick being on market next year and how that might have changed or evolved, you know, your view of the label and how that's going to position competitively. And then also how much did AAO and the feedback you got there from physicians play into this decision? Thanks.
spk03: So, look, we believe that we have a very exciting product profile at 24 months that we can bring to physicians, that they can then communicate to patients. And, of course, we believe that that positions us well competitively, right? So these are decisions that are never unique colors. I mean, many factors go into it. Competition is just a small part of that. But we wish our competitors the best of luck as well as they move forward towards… And just lastly, are you anticipating…
spk17: Without this amendment, would you have anticipated both the foveal subgroup and every other month dosing in the label regardless, or does this specifically enhance the probability of both of those being included in the label?
spk03: The answer to that is yes.
spk17: Okay.
spk03: All right, thank you. And as it relates to AAO, so look at the American Academy of Ophthalmology. As you may recall, in the month of September, we did the whole analysis to really better understand what the functional impact was of these treatments, which, as you know, because these measurements are so complicated, can be difficult to do. So at AAO, we had very exciting data on the microperimetry. But in the meantime, I think a little bit lost in the noise, quite frankly, was how good the 24-month data really was. And, you know, again, something that we believe we want to harp on, but as I said, it was a great opportunity to do that again, and we look forward to continuing that in the next year.
spk10: Thank you.
spk09: Thank you. One moment, please. Chris Howerton of Jefferies, your line is open.
spk05: Great. Thank you so much for taking the questions. I guess the first one I had was with respect to the 24-month data. If you guys could comment on the relative importance of those data being in the label itself versus a high-quality peer-reviewed journal article. And then the second question is maybe just a clarification, Cedric, in terms of, you know, how does the conversations change at the Retina Society? Because wouldn't they have already known the 24-month data, and it's really just their perception of it being in the label or another venue? So just help us understand the rationale there specifically. Thank you.
spk03: Thank you, Chris. I'm going to hand it over first to Adam to talk about the label versus article and why the label is so important.
spk04: Yeah, thanks, Chris. Good to talk to you. So obviously we have 100 field-based employees out there talking about disease day education. And they're going to be our most important voice as we get a potential approval. And the label, in my experience, is the most important document that we could ever have at Appellate. It allows those field-based teams to have a really robust conversation based on the label language with physicians. So I think that's a critical mass for us here. We're going to make sure that those conversations are as robust as possible, and that's our quickest and most nimble way of getting the data out there to the 2,600 retina doctors that we will target. Obviously, a publication of the data also supports, but we can move very quickly post-approval to have those conversations
spk03: Thank you, Adam. And then for the Retina Society, it was a great conversation. Philip, maybe you want to elaborate a little bit on that. So basically, the conversation changes at the Retina Society based on the 24 months. The implication there was that for these doctors, they know the data, but the ability to have a simplified message towards their patients for these retina docs is important. And it's important to point out as well that at Retina Society, you have the KOLs. But if you talk about the doctors that are actually practicing in rural America and all the places where we need to go as well and transmit the message, there it will be incrementally important to have this available to us.
spk05: Okay. Thanks so much.
spk09: Thank you. One moment, please. Colleen Cusey of Baird, your line is now open.
spk14: Hi, good afternoon. Thanks for taking our questions. Can you comment on how you received the feedback from the FDA on the alignment for the 24-month inclusion? Was that in writing? And how likely do you think it is that the FDA will accept the amendment? And then just given the especially short timelines of the original timeline for your NDA review, do you have a sense of if the FDA review was tracking to schedule prior to this amendment?
spk03: Thank you, Colleen. So, first of all, with respect to the first question, This was a verbal conversation with email feedback specifically on the press release that I mentioned earlier. So this was a very smooth process, to be honest with you, and we expect there to be no issues in the weeks to come where we will submit and where we will get a new PDUFA date. So then the second question, sorry, Colin, because you were breaking up a little bit, was on review tracking.
spk14: Yeah, just do you have a sense of if the NDA review was tracking to schedule prior to this amendment?
spk03: Yes, it was. So it's worth mentioning here, Colleen, again, that this was a very concentrated review timeline, right? So we had a priority review, but a priority for a type 3 NDA submission, which meant, as you know, six months from the time of submission. So everything has to be squeezed into a very short timeline between the end of July and now. And that was, as I've mentioned before, a very smooth process. But then in the end, the decision that we decided to file this amendment.
spk14: That's helpful. Thank you. And one quick follow-up. Does this change at all your thoughts on the likelihood of the FDA hosting an advisory committee meeting?
spk03: It does not. So there was no mention or discussion of an outcome.
spk14: Great. Thanks for taking our questions.
spk03: Thank you.
spk09: Thank you. One moment, please. Justin Kim of Oppenheimer, your line is open.
spk12: Hi. Good afternoon. Thanks for taking the question. Maybe just taking a step back and thinking about the landscape with some recent and upcoming data updates for systemic applications of complement. Just curious if the team had any updated thinking on targeting IgA nephropathy, perhaps with earlier stage modalities such as an oral factor B, and any of the implications of some of the siRNA combo data that's upcoming at ASH as you think about getting into clinic also next year.
spk03: Thank you so much, Justin. So, as you know, IgA nephropathy is not a focal point for us. Right now, our nephrology programs are C3 glomerulopathy and immune complex membranoproliferative glomerulonephritis. The data looks intriguing with the TACO band, of course, and we continue to look at that. I think it's a further testament to the broad potential that complement control has across a wide range of therapeutic areas. So, and the SIRNA, that's another program that we are very excited about and where we are now nearing up on an IND in the near future. Great. Thanks. Thank you.
spk09: Thank you. One moment, please. Egal Nakamovitz of CIDI.
spk08: Your line is now open.
spk21: Hey, Cedric and team. Thanks for taking the question. So I just wanted to follow up. Could you just elaborate a little bit in terms of what specifically happened internally at Appellus that enabled your regulatory team to apparently accelerate the preparation of the full 24-month data, which obviously enabled you to move faster with the EE timelines, as I understand, which then triggered a chain reaction, which allowed you to have more time to submit the 24-month data now. As I think, if I'm correct, the original expectation is that you would not be able to move quite as quickly as you ended up moving with the preparation of the 24-month data. If you could just help me sort that out, that would be great. Thank you.
spk03: Thank you, Igor. So it was a combination of multiple factors, as we outlined in the script. But on one hand, the launch timelines, which changed and which were planned for the beginning of January, the first two weeks, more or less. And then, as you mentioned, the fact that At least in September, we did not want to prioritize the filing of an amendment over the preparation of the European filing. But all these things, of course, go hand in hand with each other. The filing of Europe moved forward very well and very quickly, and the possibility of doing an amendment without hurting that effort became clear. So when we realized that the only penalty to pay here was plus or minus a few weeks, six weeks, on the current plans for the launch without a delay on the J-code and the possibility to file that amendment, that was a strong message for us. Of course, combined with the fact that our commercial team in the meantime is working very hard and considered this to be very important.
spk21: Okay, got it. That makes a lot of sense. And then maybe just to help everyone who's less familiar with the J-code process, can you just explain specifically what's the reason why that six to seven week delay between starting on January 1st versus starting the launch on you know, end of Feb, doesn't impact the timeline to getting the full permanent J-code by October. Can you just walk through the reason why that doesn't matter? Thank you.
spk03: Yes, thank you, Igor. That's a great question. So essentially, permanent J-codes get issued by quarter. And so to get the supply logistics in place and be there on time to ship your first vials is what drives that. And that is what led us to realize over the past month or two months that In all likelihood, the beginning of October was going to be the permanent J code for us. And in that context, launching, you know, in the first half of January or the second half of February does not make an impact or a difference for the J code.
spk21: Got it. Okay. Thanks.
spk09: Thank you. One moment. Ellie Merle of UBS, your line is now open.
spk16: Hey, guys. Thanks for taking the question. Just after all the interactions with the FDA, can you just speak to your confidence that GA lesion growth is still considered an approvable endpoint? I guess any reason to think that the FDA or someone within the FDA, even perhaps higher than Wiley Chambers, might be questioning the clinical meaningfulness or expressing any doubts And then just in terms of, like, the approval itself, I guess, who at the FDA signs the ultimate approval? Is it sort of with Wiley Chambers and the ophthalmology division, or could it become with someone higher? Thanks.
spk03: Thank you, Ali. So, as far as we know, nothing has changed. So, there has never been a mention at all that there is a change in the approvability or the process, and how the lesion growth is the primary endpoint. So, that is absolutely not something that I think anyone should be concerned about. So then the approval process, I believe, again, I'm kind of getting on the border now of how I understand the regulatory process to be, but at the end of the day, the division makes the determination, then Dr. Chambers signs off on it, and I believe that there is further sign of higher up in the FDA, but I don't think that that is typically a place where problems emerge. I'll speak of it that way.
spk16: Understood. Thank you.
spk03: Thank you so much.
spk09: Thank you. One moment, please. Annabelle Samimi of Stifle, your line is open.
spk11: Hi. Thanks for taking my questions. Just touched on it a little bit before, but can you just help us understand whether the FDA is going to be reviewing the 24-month data with any statistical rigor as it is the 18-month data, which is accepted, I guess, as a primary endpoint, or is it just going to be reviewed for informative purposes and then placed on the label for information so you can talk about it. I guess if that's the case, why not just wait for a publication because it seems like a lot of the physicians know this data already. They've seen it multiple times now. So I just want to understand, you know, how FDA is going to be looking at this data versus the other data that you've already submitted. Thanks.
spk03: Thank you, Annabel. So, yeah, of course, we are hopeful that, you know, that language that we got at 18 months makes us hopeful that the 24 months may indeed be considered the primary endpoint. So, you know, that in combination with the strength of the data, and again, I cannot overemphasize how powerful about getting into zip code of 30% that's extraordinary right I mean the fact that it increases the longer you treat these patients it's a really important message and creates a lot of hope and remember I mean you know at least for now I think we should all hope that that continues to go beyond year two as well the reason why this is the primary endpoints with the FDA is is that this is not a disease of two or one years, right? This is a disease where patients are affected for five or ten years, sometimes decades, right? And the long-term impact of this disease is terrible, and we're hoping to mitigate that.
spk11: So just to follow up on that, are these, I guess, are these patients or is the Okay, let me just sit back. How often does the FDA just change the endpoint? I mean, I guess that's the question. I mean, they went from 12 months to 18 months to 24 months. So is the statistical rigor as intense at 24 months as it was at 18 months as it was at 12 months? I guess that's another way of asking the question.
spk03: Well, all we know, Annabelle, is the communications that we get from the FDA, right? So we don't write those rules, and we go along with them. So that's all I can say.
spk11: Okay. Thank you.
spk03: You're welcome.
spk09: Thank you. One moment, please. Joey Stringer of Needham, your line is open.
spk18: Hey, this is Chen for Joey. Thank you for taking our questions. So, our first question is, what is your current thinking on any potential partnerships, either in the U.S. or ex-U.S., for taxative call plan in GA? And our second question is, could you help frame expectations for Paxeta-Copeland phase 2 ALS study next year. So what is the clinical meaningfulness on the, say, AFS primary endpoint? And would this trial potentially be considered registrational?
spk03: Thank you. Thank you, Zoe. So on partnerships in geographic accuracy, we are and have been preparing to launch this as well as the XUS. So that has been our plan and continues to be our plan. As it relates to the ALS study, this is, of course, a high-risk, high-reward study, right? So the likelihood of meeting the primary endpoint in that study, like all ALS studies, is going to be low. But should we meet it, of course, it would be of high, high clinical and human meaningfulness for the company and for patients. Okay.
spk22: Thank you.
spk10: Thank you.
spk09: Thank you. One moment, please.
spk08: Douglas Bao of HC Wainwright, your line is now open.
spk20: Hi, good afternoon. Thanks for taking the questions. A lot of my questions have been answered. But just curious, Cedric, in terms of the Retina Society meeting, I'm just curious, in terms of feedback you got from physicians, what was it that they most were impressed by the 24-month data? Was it safety? Was it efficacy? Was it the acceleration? I'm just curious in terms of the feedback, or maybe said a different way, what about it did the 24-month data do to change their perception that they already didn't think from the 18-month data? Thank you.
spk03: Thank you for that question, Doug, because honestly, this is why we did it, right? I mean, the The data between month 18 and 24 is absolutely remarkable and groundbreaking in the retina. I mean, we are starting to understand how this drug works in this disease. We're seeing that with those increased effects over time. Again, getting into that zip code of 30% slowdown, 30%, right, by the end phase of those two years, which is incredibly important for these patients. We also are starting to see the functional impact on these microparenteral analyses that we ran. So all of these things are important. And last but not least, of course, something that was first presented at AAO, where on the OCT images in these patients, we can also specifically look at the rate at which photoreceptor cells are lost, to really hone in on these cells that detect vision in the retina, and where we have extraordinary results as well. So all of that was very positive and important, and we are starting to really understand how this direct works, and we look forward through this major amendment to being able to talk about many of these things in the label with the broader community.
spk20: And maybe just as a quick follow-up, Cedric, of those points, was there anything that really sort of captured the imagination of the physicians at the Retina Society meeting? Thank you.
spk03: Yes, I would say what captured most of their imagination in the This gets a little bit technical, but the work that was done by our collaborator, Dr. Ursula Schmidt-Erfurth in Austria, where, again, looking at these OCT images, she looked at the photoreceptor cell loss specifically, so not the supportive cell that you have in the retina. And there, in this blinded analysis that we did, at the one-year time point, both in Derby as well as in Oaks, requires more to be done, of course, but I think that retina docs, looking at that and understanding how the mechanism works is very helpful. And Adam would like to add something to that as well.
spk04: Yeah, Doug, I just thought it would be interesting for you, you're asking about the Retina Society meeting, but also our 24-month data market research. I'll summarize the overall feedback from that market research, which is with retina specialists, opinion leaders, as well as those that potentially don't go to those type of meetings. At 24 months, there was a really strong conviction towards the therapeutic effect, and Derby's near-miss at month 12 became irrelevant to those physicians that we used within the market research. From an efficacy perspective, they were impressed by the longevity and the consistency of the efficacy curve separation across both studies. And they started to really appreciate the robustness of the clinical data. And, you know, we continue to get quotes during that market research such as, it's impressive that the effect of treatment is increasing with time. It's just really impressive. We kept getting that impressive word was the one that came out. The effect was already proven after six months, but we're speaking about reductions of about 30% after 24 months. That type of feedback
spk20: Okay, great. Thank you very much. That's super helpful. Thank you so much, Doug.
spk09: Thank you. One moment, please. Our last question comes from Madhu Kumar of Goldman Sachs.
spk08: Your line is open.
spk00: Hey, guys. It's Rob on again. Just one other question we had was, Is there any impact from the IRA, the Inflation Reduction Act, in moving the approval potentially back to 2023?
spk03: Thank you so much, Rob. You're double dipping here. I like that. No, so this was not a consideration in our decision-making process. And look, it's understandable that this comes late. It generates confusion. But when the circumstances are there, and they always evolve, and they're never kind of one circumstance, but several things, when we get to a point where we truly believe that it's going to be better for patients and for physicians, sometimes you have to make difficult choices. And doing it now close to the Vesuvia is not ideal, but we believe it's going to be serving us very well as the next year comes. So thank you for your question. And is there anybody else after you, operator?
spk08: That's all. That concludes our Q&A.
spk03: Thank you so much. So in closing, thank you all for joining us today. We are around later today and tomorrow. And if you have any additional questions, please feel free to reach out to Meredith.
spk08: Thank you for your participation in today's conference. This concludes the program. You may now disconnect.
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