Apellis Pharmaceuticals, Inc.

Q1 2023 Earnings Conference Call


spk02: Good day, and thank you for standing by. Welcome to the Q1 2023 Appellate Pharmaceuticals Earnings Conference 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 this session, you'll need to press star 1-1 on your telephone. You will then hear an automated message advising that your hand is raised. To withdraw your question, please press star 11 again. Please be advised that today's conference is being recorded. I'd now like to hand the conference over to your speaker today, Meredith Kaya. Please go ahead.
spk20: Good afternoon, and thank you for joining us to discuss Appellus' first quarter 2023 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. Caroline Baumel, 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.
spk01: Thank you, Meredith, and thank you all for joining us today. I know that the launch of Cyphovry is top of mind for everyone, so let me jump right in. We received FDA approval of Cyphovry for the treatment of geographic atrophy on February 17th. Cyphovry is the first and only treatment available for GA, a disease that affects more than 1 million patients in the US alone and that relentlessly and inevitably leads to vision loss. Prescribing label details Cyphovry's proven ability to slow GA progression with increasing effects over a 24-month period, flexible dosing, and a well-demonstrated safety profile following nearly 12,000 injections. This approval is the culmination of more than 20 years of hard work and dedication by our team, and we are incredibly proud to bring Cyphovry to patients who, until now, had no treatment options. Cyphovry was launched in the US on March 1st. In that first month, just over 6,000 commercial vials were shipped to physicians and Cyphovry generated US net product sales of $18.4 million for the first quarter. We are continuing to see the strong momentum in the second quarter so far and are really encouraged by this early market adoption. Initial demand by both eye care professionals as well as patients has exceeded our expectations and we view this strong start as a leading indicator of longer term demand. However, let me temper this by saying that GA is a new uncharted category. We have been in the market for two months and are just starting to learn about how various adoption trends may impact demand. So while we are pleased with our progress in March, We anticipate fluctuations in uptake throughout the temporary J-code period. Caroline and Adam will provide more color on what we are seeing in the market, some of the recent functional analyses presented at ARVO, and our progress with the commercial launch. We are also making important steps in our efforts to bring intravitreal pexitacoplan to patients globally, with applications now under review in the European Union, Australia, Switzerland, Canada, and the United Kingdom. Turning now to Empaveli. We are continuing to see strong momentum with Empaveli as we close out its second year on the market. US net product sales were $20.4 million in the first quarter. We were pleased with the approval of our supplemental NDA, which includes the Pegasus and Prince results, and look forward to the potential approval of the Empaveli injector. What really continues to stand out are the compliance rates for Empavedi, which remain around 98%. This is outstanding for a drug this far into its launch, and we view it as a clear testament to how much better patients feel when taking Empavedi. In ALS, we recently made the tough decision to discontinue treatment in the open-label portion of the Phase 2 study following a recommendation by an independent data monitoring committee. The committee's recommendation was not based on any unexpected safety signals. All patients in the study have completed the randomized treatment period, and we will analyze the data as planned. I would like to say thank you to the people living with ALS and their caregivers who participated in this study, and for the partnerships we have built within the ALS community. We continue to advance nearly a dozen clinical and preclinical programs, and you'll hear more about some of these today. Overall, we believe we have only just begun to unlock the potential of complement science and look forward to sharing our continued progress with you going forward. With that, I will turn it over to Adam. Thank you, Cedric.
spk12: I am thrilled with the initial enthusiasm that physicians and patients are showing for SIFOBRI. As I shared on the approval call in February, we have built best-in-class commercial and medical teams with extensive experience in retina. They went into the SIFOBRI launch well-prepared and highly energized, and they have shown flawless execution on the launch to date. On day one, our commercial leaders joined 10 retina specialists as they treated their first patients, providing us an opportunity to gain operational insights and feedback. Many retina specialists posted about their experience on social media, recognizing the importance for patients and the historical nature of the first ever approved treatment for GA. Let me share some of the initial metrics from March. The commercial and medical teams engaged with nearly 2,000 physicians at least once, and we have now seen syphobry orders within every sales territory. 6,000 commercial syphobry vials were shipped to physicians. In addition to commercial vials, we also distributed more than 3,400 samples to physicians upon request, which is an important indicator of future demand. We have also seen several academic institutions put sci-fobry on formulary, which is faster than we expected. And as planned, we submitted our application for a permanent J-code to CMS and expect to receive our code in early October. In summary, the launch is off to an excellent start and we're encouraged by what we are seeing already in Q2. A significant amount of demand has come from private equity-backed groups. However, the majority of demand to date is coming from independent, non-PE-backed practices, which tells us that there is real patient demand across the country. But as Cedric said earlier, while it's exciting to see these initial positive indicators, it is still early in a disease category that has had no approved treatments until Cyphovry. Samples will continue to be an important component of the launch, representing a meaningful proportion of overall files. And we have more to learn about market adoption and how certain factors such as reimbursement and dosing frequency may impact demand. As a result, we should expect some bumpiness in both demand and sales until we obtain the permanent J-code. Looking forward, the teams are focused on continuing to educate both physicians and patients on syphobry and geographic atrophy. We have been particularly encouraged by the patient requests for treatment. The media coverage, especially the segment on CBS Morning, was a strong push for patients to reach out to their physicians and ask about syphobry. We will continue to educate patients with GA through our physician engagement, as well as through our GA direct-to-consumer campaign, which is aimed at encouraging patients to monitor and talk to their eye doctor about vision changes. Now, turning to Empaveli. In the second half of 2022, We expanded our field team and strengthened our partnerships with key centers. Our efforts are taking hold as there were more than 200 patients on therapy at the end of the first quarter. We are gaining momentum in 2023 to date as we received FDA approval of the SNDA with the phase three Prince results and the 48 week phase three Pegasus data. which enables us to have even more robust discussions with physicians about the effects of Empaveli. We are also looking forward to the potential approval of the Empaveli injector, which we believe will significantly improve the patient's experience on therapy. Now, let me turn the call over to Caroline.
spk19: Thank you, Adam, and good afternoon, everyone. It has been a tremendous start to my journey at Appellus. Following the approval of Cyphovry, I am proud to see my fellow physicians and peers embracing the transformative potential of Cyphovry on patients' lives. I have attended several retina meetings since the launch, and the feedback from my retina colleagues has been positive. Just last week, we were at the Association for Research in Vision and Ophthalmology, or ARVO, Apellis had a strong presence with eight presentations showcasing our leadership in GA and retina. At this meeting, we shared new phase three post hoc functional analyses. In a presentation given by Dr. Alan Chang, patients with extra foveal lesions who were treated with cyphovary showed a visual function and quality of life benefit. Results demonstrated a preservation of 5.6 letters compared to sham, which is equivalent to more than one line of vision, as measured by best corrected visual acuity, or BCVA, over 24 months. Patients also reported a clinically meaningful benefit on VF225, a validated visual function questionnaire which measures quality of life outcomes such as social function, driving, and dependency on others. And in a separate presentation given by Dr. Ursula Schmidt-Erfurth, patients treated with syphovary demonstrated a substantial reduction in photoreceptor cell loss as compared to sham. Data were also consistent when comparing syphovary-treated study eyes to the untreated fellow eyes. Remember that both retinal pigment epithelial, or RPE, and photoreceptor cells are required for visual function. RPE cells maintain the integrity of photoreceptor cells, which are the light-sensitive cells responsible for vision. We are also continuing to progress our three-year Gale Extension study and look forward to sharing data from this study in upcoming medical meetings. Now that Siphovery is approved in GA, we are exploring other indications where intravitreal PEG-set Copeland may offer value for patients, such as Stargardt disease. We also plan to evaluate the impact of Cyphovir in those patients who are on the verge of developing GA, and specifically the impact Cyphovir has on preventing photoreceptor loss in these early stages of disease. In the rare disease space, we and our partner SOBE are continuing to advance Empaveli in additional indications. We are enrolling patients in a phase 3 trial for immune complex membranoproliferative glomerulonephritis and C3 glomerulopathy, both rare kidney diseases. And Sylvia is enrolling patients in a phase 3 trial for cold agglutinin disease, a rare type of autoimmune hemolytic anemia, and in a phase 2 trial for hematopoietic stem cell transplantation associated thrombotic microangiopathy. a severe and common complication following hematopoietic stem cell transplants. I will now turn the call over to Tim for a review of the financials. Tim?
spk05: Thank you, Caroline. Since we issued a press release earlier today with the full financial results, I will just focus on the highlights for the first quarter of 2023. Total revenue was $44.8 million, which consisted of $20.4 million in Empaveli net product revenue, $18.4 million in Sifovri net product revenue, and the remainder in collaboration revenue from SoBe. A few comments on Sifovri. Like Empaveli, revenue for Sifovri is recorded when it is shipped to the distributor, not when it is shipped to the physician. Therefore, revenue includes both product shipped to the physician and product in the channel. We estimate approximately two to three weeks of inventory on hand at the distributor and expect these to be the inventory levels going forward based on anticipated future demand. We are not guiding on gross to net, other than to say we anticipate it will be within the standard pharmaceutical ranges. And as you've heard already, we are in the early days of the SIFO relaunch and do not expect that one month's results represent the full year's runway. We intend to share more about our learnings in the coming quarters. Turning to the rest of the P&L, R&D expenses were $110 million and G&A expenses were $102 million, and we reported a net loss of $178 million. As of March 31, 2023, Pellis had $765 million in cash and cash equivalents, which includes the recent follow-on offering completed in February. We expect our current cash balance to fund our operations into the first quarter of 2025. including the ongoing EMPA Valley and SIFO relaunches and further development of our pipeline. We remain confident in Appellus' 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?
spk01: Thank you, Tim. This is an incredibly important and exciting time for our company. With SIFO now available for patients, we are blazing a new trail in GA. and our position in the P&H market is expanding. Additionally, we continue to advance a robust clinical pipeline encompassing multiple late-stage rare disease programs as well as several programs heading into the clinic. This broad portfolio gives us a position of strength as we strive to achieve our vision of being the global leader in complement. Let us now open the call for questions. Operator?
spk02: Thank you. At this time, we'll conduct the question and answer session. As a reminder, to ask a question, you'll need to press star 1 1 on your telephone and wait for your name to be announced. To withdraw your question, please press star 1 1 again. We ask that you please limit yourself to one question and one follow up. Please stand by while we compile the roster. Our first question will come from the line of Madhu Kumar of Goldman Sachs. Madhu, your line is now open.
spk08: Okay. Thanks for taking our question. So maybe to follow up about some of the comments Adam made around future quarters, like what do you think is a way to think about this lumpiness in a very practical way? Do you think this is a way to think about a kind of like growth and decline or kind of a flattening? Or how should we look at kind of where the launch will be in terms of lumpiness? Is it lumpiness across the quarter or kind of lumpiness into the April kind of numbers you have so far? Suggest some variants on lumpiness. And then I have a follow-up afterwards for Tim.
spk01: Thank you, Madhu. Great to hear you.
spk12: I will let Adam comment on this. Thanks, Manu. Thanks for your question. Obviously, we're thrilled with the first quarter sales and the 18.4 million. And more importantly for me, the 6,000 commercial demand files, that's a real strong indicator with the 3,400 samples that also went out about demand. And we're continuing to see that momentum into 2Q so far. So everything's progressing really well. I will say, obviously, keep in mind that GA is relatively new. It's uncharted category. We've only been on the market for two months, and we're starting to learn about the various adoption trends, and some of those may impact demand. We have a little bit more to learn around reimbursement, dosing frequency, et cetera. So that leads to a little bit of the bumpiness until we get to our permanent J code in October. Now, Tim, you might want to comment a little bit on one way of running that forward from a forecaster's
spk05: Sure. So the way we think about it is, you know, the first quarter numbers really are kind of a five-week month, if you will. So if you take that 6,000 or so vials and divide that over five weeks, it's roughly 1,200 vials per week. And we look at this as sort of an average weekly growth rate potential in terms of forecasting. So you can do what you want with that. Obviously, there is a portion of the vials that we recognize as revenue that's in a distributor because those are included in our revenue numbers. And we'd like to, you know, basically the distributors like to keep roughly two to three weeks on hand. So as you grow that sort of those vials that go out to the retinal specialists on a weekly basis, you also have to grow that inventory a little bit. But that's how we like to think about it. But again, each week is different and we've seen some lumpiness as Adam said, but we have seen continued strong demand in April.
spk08: Okay, great. So maybe to follow from that, So as you think about this one Q number, which is basically one month of sales, how does this shift or kind of refine your perspective about a path to breakeven for Appellus as a company overall?
spk05: Yeah, sure. So we obviously forecast a number of different scenarios. This is the best case scenario. And when we guide to our kind of cash runway, we take a conservative view. Again, it's early, so we're going to continue to evaluate this. But, you know, again, like I said, that's a conservative number, that first quarter of 2025. So, you know, we'll see.
spk08: Okay, I guess maybe one more to follow up on that. Is there any kind of external leverage you think you guys have that could kind of move things further or could actually get you to have a little more clarity on kind of a path to break even?
spk05: Yeah, I think we've been really creative in terms of how we finance the company and how we've managed our, you know, I think we've managed our expenses, especially in terms of the, you know, when we finance and how we've kind of built out that commercial infrastructure relative to when our approval came. So, look, I think we're pretty careful about this, but I don't think we can guide specifically on, you know, how we're going to bridge that gap to profitability. But, you know, we're pretty confident it will be the right thing for shareholders when we do that.
spk08: Okay, great. Thanks very much, everybody. Thanks, Madhu.
spk02: Thank you. One moment for our next question. Our next question comes from the line of John Miller of Evercore. Your line is open, John.
spk11: Hi, guys. Thanks for taking my question, and congrats on a great first quarter number. I think you actually gave a lot of great color on the dynamics there, but I'd love to dive into that Arvo presentation, actually. I would love to get a sense for how you view the impact of functional post-hoc analyses on the commercial market from here. And maybe if you could provide a little bit more color on where those functional analysis cutoffs came from. Where did 250 micron cutoff for folio, postfolio come from, et cetera? And did you run the time to event analysis like your competitor did?
spk01: Thank you, John. Well, I'll start off by giving the word to Caroline to talk about
spk19: Thank you, Cedric. You know, we've always believed that there is a link between the functional data and flowing the growth of geographic atrophy. And sometimes post-hoc analysis are necessary to confirm that, especially within the noise of the measurements that we get in patients with GA. In our post-hoc analysis, we showed that there was a functional benefit with regards to visual acuity and quality of life measurements demonstrated in such over-treated eyes with extra foveal lesions. And this is really consistent with what I would expect as a clinician, that we would be able to show this benefit in patients before the lesions affected the fovea. 250 microns, well, that is the size of the fovea-lay vascular zone. And, you know, why didn't we do the same analysis as Iveric? I think that we're pleased that they were able to do the type of analysis that they did to show their benefit. And we have our recent functional analysis, and we also have micro-perimetry data that was presented at Argo last year that confirms our functional benefit.
spk12: Hey, John. It's Adam. Just following up. Obviously, the commercial team is laser-focused on executing against our label. So all of our focus is there and targeting our 2,600 retina doctors around the U.S. So while this is great data, I think there's a great usage from educating the medical community, but our sales team is focused on executing our plan and talking about our 24-month data and everything that's within our label.
spk11: Just as a quick follow-up, guys, will you be including that functional analysis in your XUS filings? I know there's been a lot of attention from the EU, especially on functional data.
spk01: Absolutely, we will. So, you know, it is part of the bigger functional story. More functional data will come. to see if it relates.
spk11: Thanks so much, guys. Congrats again.
spk02: Thank you. One moment for our next question. Our next question comes from the line of Tezeen Hamad of B of A. Your line is open.
spk18: Hi guys, good afternoon and congrats from me as well on a really good start to the launch. I'm just wondering how much details do you get about the granularity? So you shipped 6,000 plus files. Do you get in real time updates on how many of those files are actually being used? And is it your expectation that the initial grouping of patients that are going to be put on the drug will be every month dose versus every other month, and then have a follow-up. Thanks.
spk01: Thank you, Tazine.
spk12: Adam? Yeah. Hey, Tazine. It's Adam. So, obviously, what we do see in this initial phases of the launch is vials ordered by a retina practice, and then the link to that is the revenue number that you've seen. So, initially, All of our feedback is based on an interaction from either someone from the medical affairs team or the commercial team having a discussion with the physician. But we don't see that level of granular detail of, you know, how these vials are used or what type of patients they're used in. What I can tell you is that, you know, we expect physicians to carry only one to two weeks of stock in their fridge. So my belief is the vast majority of those demand vials, as I call them, the 6,000 commercial and the 3,400 samples, in the first month are likely going into eyes relatively quickly. The second part of your question was what type of patients and is monthly or every other month likely to be dominant? So what we are hearing anecdotally is it's the type of patients that physicians are using Sifo-Re4 as we expected within the initial phases prior to launch. You tend to hear physicians say that they're treating a patient who's blind in one eye and GA is progressing, vision loss in the second eye, wet AMD in one eye and GA in the second eye, and bilateral GA. That was consistent with our market research. And we are also hearing that every other month, it's a bit of a game changer in this disease. And every other month is the dominant player at the moment. So hopefully that answers your question.
spk18: Okay. Yeah, that's helpful, Adam. And then just with the recent news that Astellas would be managing the next complement launch, if it does get approved, what's your view of them being your competitor in this market? Thanks.
spk01: Thank you, Tessie. Well, first of all, we're happy for both Astellas and for Iberic, and we wish them a very good and productive partnership together. From our angle, it doesn't change anything. We are very focused on the job at hand at making Sifovir available to every patient in need in the U.S. for now and other countries in the future. So, importantly, you know, we have the every other month dosing, of course, which gives us, we believe, an important competitive advantage that we view materializing in the months to come as well.
spk21: Okay. Thank you.
spk02: Thank you. One moment for our next question. This question comes from the line of Anupam Rama with JP Morgan. Your line is now open.
spk04: Hey, guys. Thanks so much for taking the question, and congrats on the initial launch here. I have a quick question on syphilis sampling. When a physician asks for samples, like how many samples do you give per patient, and I guess what is assumed in terms of that patient transitioning to commercial drug, you know, the timeframe? switch to commercial drug. Thanks so much.
spk01: Thank you. I'm great hearing you, Adam.
spk12: Yeah. Hey, Adam. Thanks for your question. So, obviously, samples are a really important component of our launch, and they're going to represent a meaningful proportion of overall files. Now, physicians tend to request samples, and the reason why they do so is that they want to understand the patient's clinical experience with the drug, gain experience with the drug, and also learn how to administer it as it's a new drug in this class. A few things, obviously, only a physician who has a medical certification can file to receive samples, and they have to form their request to do so. So they tend to know the level of samples they need based on how they want to use it, and we expect it's an important piece of our business moving forward as we progress towards the permanent J-code. Now, I do think the majority of samples lead to commercial vials in the end. Caroline, from your perspective, is there anything you want to add?
spk19: Well, I think samples are important for physicians. They fill a gap and also gives us an experience with how to use the medication. And my colleagues have been really pleased to have this option available. They're excited to finally have this treatment for GA. I think the flexible label meets all of their needs, and they're really having a great interaction with Appellus. That's my input so far.
spk21: Thank you. Thanks so much. Thank you. Thank you.
spk02: One moment for our next question. This question comes from the line of Colleen Cousy with Baird. Your line is now open. Great.
spk18: Good afternoon. Thanks for taking our questions, and congrats on the quarter. So of the 6,000 demand vials, as Adam called them, and the 3,400 samples, how many different prescribers does that cover? Kind of what's the breadth of prescribers you're seeing in this early stage?
spk01: Thank you, Colleen. Handing it over to Adam.
spk12: Yes. Hi Colleen, it's Adam. So obviously we're targeting 2,600 retina physicians and we continue to do that. The commercial and medical teams, they've engaged already 2,000 physicians at least once. And the thrill for me is that actually every sales territory has actually ordered a commercial vial of Sly Fovry. So we're getting usage across the whole of the country. We're also seeing usage from private X-ray-backed practices, but the majority is coming from independent practices. So again, a good mix of the type of center that's using. Now, the challenge we have initially in the early stages of this launch is that we only see vials going to centers. So we don't have a physician-by-physician knowledge of who's using, apart from anecdotal. But physicians are wanting to speak to us, and we're already getting through our 2,600 target list. I think there's a wide spread of physicians who are using across the country.
spk18: That's helpful, thank you. And then just as a follow up, can you remind us your strategy for distribution? How many distributors you're working with and could we expect more to come online in the future?
spk12: Yeah, thanks Colleen, it's Adam too. So we're not public on our distribution strategy, but we have all of the distributors that meet the needs of all of our 2,600 physicians. and all of the coverage plans that they may have. So, we're very happy with our distribution process at the moment, but we're not public on it.
spk18: Got it. Thanks so much for taking our questions, and congrats again.
spk01: Thank you, Colleen.
spk02: Thank you. One moment for our next question. This question comes from the line of . From Citigroup, your line is now open.
spk10: Hi, Cedric and team. Congrats on the very strong launch. Just a really basic question, just so I'm clear. The WAC is $21.90 per vial, and you've done $6,000 or maybe a little more vials. So that's getting me to $13 million. So I must be missing something. Can you just clarify how you're getting $18.4 from the just over $6,000 commercial, please? Thanks.
spk05: Sure. Hey, you guys, Tim, I'll take that. So we recognize revenue when the vials are shipped. They go to the distributor, and then the distributor will, you know, when the doctor requests them, the distributor will ship them to the doctor. And so the $6,000 is that second step, but we recognize revenue with the first step. So there are some that stay at the distributor level that we've already recognized as revenue. But we won't tell you what those vials are.
spk12: And you got this out of, just as a reminder, right? We expect our distributors to keep between two to three weeks of inventory on hand and physicians about one to two weeks.
spk10: Okay. So there's another two to three weeks of distributor revenue that's not in the 6,000. Okay. And then regarding the sampling, can you give us a sense as to what percent of the 2,000 physicians that you've engaged with so far have actually requested samples?
spk12: Yeah, so we've seen samples being used across the vast number of those 2,000 physicians that we've seen there across all of our regions in all of our geographies.
spk10: Okay, and then we've talked in the past about the dynamic with so-called recalendaring some of the wet AMV patients to make room for cyphover capacity. Have you seen any evidence of that practice yet?
spk12: Yeah, we've seen and anecdotally heard that physicians are looking at managing both their wet AMD patients as well as their GA patients and managing the calendars there. Caroline, anything you want to add from your experience?
spk19: Well, I think that this has fit really nicely within the treatment paradigm that we already have with anti-VEGF. And so it's well into that. Doctors or physicians are really enjoying our educational materials for patients, the brochures that they have. and able to explain this to patients. And patients are really enthusiastic about this treatment. They recognize that their vision was going down before, and we want to save and reduce the burden of GA. But as retina physicians and retinal surgeons, we know how to adapt to treat our patients, and I have no doubt that my colleagues will be able to adapt to these increased injection burdens, finding new ways to do that.
spk10: Great. Thank you. Thank you.
spk02: Thank you. One moment for our next question. This question comes in the line of Steven Seedhouse with Raymond James. Your line is now open.
spk14: Thank you. Good afternoon and congratulations. I wanted to ask, there have been various news reports, of course, discussing strategic takeover interest in Apellis. So, Cedric, any comments you wanted to make on that subject and Apellis' strategic priorities? Thanks.
spk01: Yeah, thank you, Steve. Well, there's always a lot of speculation. Of course, we are, you know, in a stage of commercialization that draws a lot of interest, but we are squarely focused on making Cyphovri available to every patient in need in the U.S.
spk14: Roger that. Can I follow up and just ask the – when is the first update from Gale coming, and what would that initial data sort of entail, if you can just get us current on that? Thanks.
spk01: So, we are going to be presenting a full update on Gale at the ASRS conference at the end of July. Very excited about sharing, you know, what happens to increasing effects over time that you know, mentioned already, it's a 24-month data, so this is going to be the 30-month update on the subject as they continue to be done.
spk21: Thanks so much.
spk17: Thank you.
spk21: Thank you. One moment, please.
spk02: Our next question comes from the line of Phil Nadu with TD Cohen. Your line is now open.
spk13: Good afternoon. Let us add our congratulations on the initial launch of Cyphovry. A couple questions from us. First, Adam, I think you mentioned that you expect physicians to keep one to two weeks of inventory on hand. So with 1,200 vials approximately per week, you should have seen some reorders during March. Would you be willing to share the proportion of those 6,000 that were reorders versus first-time orders?
spk12: Hey, Phil, thanks for the question. Yes, we've seen reorders, but we're not going to go into the details of those reorders
spk13: Got it. And then second question, there were recent reports about endophthalmitis. It seems like something that's going to happen at a background rate. How should investors put into context any future errors, database settings of endophthalmitis or other side effects?
spk01: Thank you, Phil. I'll let Caroline answer that question.
spk19: Thank you. There was a single case of culture-positive endophthalmitis, and that was deemed related to the intravitreal injection procedure. This is well within the reported rates based on the number of intravitreal injections performed thus far. And as you had mentioned, it was misquoted as blindness and FAERS, and this is being corrected. I'd say that overall, we are encouraged by the safety profile thus far with Cytovery, and this has been consistent with the clinical trial.
spk13: Perfect. Thanks for taking our questions and congrats again.
spk02: Thank you. One moment, please. Our next question comes from the line of Justin Kim of Oppenheimer. Your line is now open.
spk07: Hi. Thanks for taking the question and congrats on the quarter. Maybe just following up on the observed initial adopters of therapy for staph ovary, is there a lag in reaching patients with GA in a single eye and nothing in the lateral eye? Is that driven by the fact that these patients might not be seen by a retinal specialist and maybe even just being seen by an optometrist or an ophthalmologist?
spk01: Thank you so much, Justin. Great to hear you. Adam, I don't think I can share too much.
spk12: Yeah, thanks, Justin. Good to talk to you. So, yeah, based on our initial research we did prior to launch and the feedback we're hearing from physicians, the prioritized patients that I described earlier in the call tended to be the first wave of treatment purely because they sat on the books of retina physicians. So, your assumption can be quite accurate that a lot of these physicians that have, you know, GAN1I that might be a Extraphobia and not impacting vision might tend to have been sent back to their ophthalmologist or their optometrist. Now, moving forward, we believe that, you know, you might have seen that we're doing some direct-to-consumer work with Henry Winkler, and we're launching the GA One Weight Campaign. It's a really important part of our marketing strategy. We think that a lot of people basically believe, particularly the elderly, that vision loss is just a natural part of their aging. And what we want to do is we want to drive those patients to go and see their eye doctor. So our GA won't wait campaign is going to be a really important tool for us to educate patients and move patients to go and see their physicians. And we're really thrilled that Henry Winkler has decided to partner with us because of his really emotional story of looking after his father-in-law as his father-in-law went through vision loss. So that will help us, and that addresses the piece of your question about patients not naturally sitting with the retinotoxin.
spk07: Okay, great. And maybe just to follow up, you know, maybe thinking about safety for Empaveli, any updates on the meningococcal infection profile and if there's any update on there given sort of the profile to date?
spk01: Yeah, no, thank you so much. So with Empaveli, I mean, unfortunately, we have crossed into north of 1,000 patient years of dosing. case of a new cochlear infection. And Adam, I don't know if you want to add something to that, but we're extremely happy with what we've seen so far.
spk12: No, it's great. Thank you, Justin, for asking an Empavelli question. I think it's a massive, massive fan of all things Empavelli and PNH, and I think we're making great progress there. So as Cedric said, you know, we still know cases over 1,000 patient years, and we still see really, really high compliance, 98%. It shows me that the to be a strong driver within the P&H market. So I'm thrilled with what that team is doing, and they continue to make great growth quarter on quarter. All right, great.
spk07: Thanks so much, everyone. Thank you.
spk02: Thank you. One moment for our next question. This question comes from the line of Derek Aquila. With Wells Fargo, your line is now open.
spk06: Hey, everyone, and congrats on the quarter. Well done. Just a couple questions from us. So maybe just first off, I was kind of wondering if you got any feedback from physicians kind of on how the patient journey and the logistics are working in the practices. So, you know, how has SIFO re-impacted their practices, and are you finding areas to optimize, you know, for future in the launch? And then the second question, and maybe I missed this earlier, How long do you plan to actually run the sampling program? Thanks.
spk01: Thank you so much. Well, I will hand the physician feedback one to Caroline, and then Adam will talk about the sampling.
spk19: Well, the physician feedback has been really positive. It's amazing that Appellus and my colleagues as a company, relatively new to the retina space, has contacted and impressed so many of my colleagues You know, I don't know anyone who doesn't know the members of the Pellis team who contacted them for medical and sales information. So I think that that's all helped bring the patient's story into light, and patients are really pleased with their initial interaction with Cyclovir.
spk12: Yeah, I think you said it nicely there, Caroline. Hey, Derek, it's Adam. So, yes, sampling, we still believe it's going to be pretty important for us during this launch phase, particularly before we get a permanent J-code in October. And as I said previously, just in case you did miss it, some of, you know, physicians want to gain a bit of experience. They want to try the drug, make sure that, you know, when they've got a patient in the chair that they understand how everything goes, et cetera. So it's going to be an important tool for us. I do see samples as a sign of demand.
spk06: Got it. And maybe just one follow-up to my first question. So, I guess, you know, is there any kind of pushback or issues with, like, the time in the chair for these patients as, you know, again, the communication, the education around SIFO ovary? I just, you know, kind of compared to wet AMD, you know, we've heard some feedback on that. So, just kind of curious what you're hearing as well. Thanks.
spk19: Well, this is really an opportunity to change the treatment paradigms. I mean, I think back to when we initially had treatments for wet AMD. It was the same sort of thing. We had to explain to patients they were having an injection. We had to educate patients. And we were able to completely change wet AMD from a blinding disease to something where we see patients earlier. We have all eye care providers involved, and we can save vision. So, you know, now that we have SipoVir, it's the first treatment for GA, we're able to start the treatment paradigm for GA and and kind of roll it back so we can start to treat these patients earlier, get all eye care providers involved, not just retina docs, but cataract docs, optometrists, you know, geriatricians, and treat these patients. And I haven't really heard anything, but of course, anything new takes a little bit of education for patients in the community.
spk12: Hey, Derek, it's Adam. I'll just jump in on there too, right? So obviously, we were doing disease stay education from the end of last year. So we've done a really solid job with our field teams to educate physicians, centers, and also patients compliantly around geographic atrophy. Anecdotal feedback from all the physicians that we've been speaking to have been using is that patient-physician conversation goes incredibly well. These patients are educated, they're very comfortable within the chair, and physicians are doing a really solid job of describing syphovary in the disease. So So far, those conversations have been going very, very well.
spk06: Super helpful. Thanks, guys, and congrats again.
spk02: Thank you. One moment for our next question. This question comes in the line of Ellie Merle with UBS. Your line is now open.
spk15: Hey, guys. Thanks so much for taking the question, and congrats on all the progress. Maybe just a couple on Europe. Just first on the regulatory review, can you any color that you can provide on how the European review is going and any feedback that you've gotten and the latest there in terms of your confidence on European approval? And then second, just in terms of the commercialization strategy in Europe, I guess how should we think about the commercial opportunity and strategy ex-U.S., versus the U.S. and any key differences there. And then just on the ex-U.S. commercial preparations and build-out, can you comment just where you are on that front, both in terms of the Salesforce build-out and your commercial preparations, but then also from a spend perspective, where you are in terms of the ex-U.S. build-out? Thanks.
spk01: Thank you so much, Ellie. Great hearing you. Well, look, I mean, Europe is the next frontier, the rest of the world as well. I mean, we have... as well. European regulatory process is going as we had expected and going very well. We expect an approval there early next year. And I think it's important to point out that we established our commercialization force in Europe many, many years ago. So Adam has been with us, I believe, longer than four years now. And as soon as he came in, we established our force in Zug, Switzerland. This is important because in Europe, as many of you know, the work involves many, many layers. So there is a whole level of awareness that needs to be established, not just with the retina doctors, but also with regulators, which of course EMEA has its supporters, but you know, regulators, the payers, and quite frankly, also kind of the political landscape for people to understand what this disease is and how we are going to bring this to the market. And Adam will talk a little bit more about how we have gone about that.
spk12: Hey Ellie, it's Adam. So yeah, obviously 5 million GA patients worldwide. And if your assumption is one to 1.2 million of those are in the US, you can see there's a massive opportunity for us ex-US. So as Cedric beautifully said, right, we've been building out the commercial and medical affairs infrastructure. Our corporate European office is based in Zug in Switzerland. That's where our strategy is driven from. And we started to put feet on the ground from a medical affairs and country leadership perspective in the UK, France, Italy, Nordics, and more importantly, our first potential launch outside of the US, Germany. And we also have footprints in Canada and Australia. So we're getting ready for this launch. We're also going to do it in a very appellate way, right? We're going to be super thoughtful in when we onboard people and we'll wait for milestones as we go through the European regulatory process. We've been really lucky in attracting very talented people to join our teams. So we're ready to go as we work towards a potential approval towards the end of the year.
spk21: Great, thanks.
spk07: Thank you, Eddie.
spk02: Thank you. One moment for our next question. This question comes from the line of Annabelle Samami with Steeple. Your line is now open.
spk16: Hi, thanks for taking my question and great quarter. Congratulations. So I want to go back to the functional data that was presented at Arvo. Clearly it's the first evidence of function that you demonstrated in addition to the anatomical data. So I guess the first question is what was the reception that you got from the physician population at Arvo? And I guess given that the benefit was seen in patients who are earlier or have lesions that are further away from the center, so technically extra foveal. How does that square with your current strategy of targeting patients? Do you think that there's going to be a shift to maybe go earlier since you're seeing the functional benefit there? And then the follow-up is, I noticed that you mentioned that you're going to be exploring the drug in patients that are at risk of developing GA. Is this different from intermediate disease, which I thought that you had moved away from a little bit? So, yeah, just if you could help us understand any change in strategy based on the interesting information you presented at ARVO. Thanks.
spk01: Thank you. Thank you, Annabelle. Well, I will let Caroline comment on the reception, but I think it's important for people to remember that visual acuity is only the measurement of central vision. visual function is much, much more than just your ability to read a Snellen chart. And I always give the example, imagine walking through New York, looking through a straw. You would have 20-20 vision on a Snellen chart, but obviously your function and your ability to operate would be severely impaired. So with that context in mind, the visual acuity is determined by the presence of photoreceptors within the fovea. So when we look at visual acuity and you look at extra foveal patients, that means that these patients at baseline in the study still theoretically have the ability to have central vision. And then the question, does that central vision get impaired over time? And can we slow that down? So in that sense, it was a very important study. But again, within the limitations of how we measure function, just focused on that element of visual acuity. You may recall that last year in September, we presented data on microparametry. That is something that looks more at the periphery. So then the question as it relates to intermediate AMD versus the risk of GA, you bring up an excellent point, which is that one of the most appealing features of site for ovary are the increasing effects over time. So the ability to slow down the progression of the disease increases when you go into year three. So the longer you treat, the better it appears that this drug is able to slow down the progression of GA. And hence, the ability to treat as early as possible is important. Intermediate AMD is a term that gets used randomly and not very precisely, all the way for patients who have just bruising in the eye to patients that may have kind of the early onset of geographic atrophy. What we did in an intermediate AMD, and this is direct neither an indication or an endpoint. I cannot overemphasize that. So in that context, what we want to do is go treat as early as possible before you actually have the presence of geographic atrophy. So we can do that now with OCT imaging, and that's where we want to go next to study what safe ovary can do. So Caroline, if you want to maybe briefly comment on the feedback that you got on the functional endpoint.
spk19: Thank you, Cedric. I would say the feedback was very positive. And because it really is consistent with what we would expect as a clinician. For example, when we see patients and they have GA through the fovea, or any patient who has a severe disease, the visual acuity measurements can have a lot of noise and be really variable. And so we would expect to have more stable and reproducible visual results as the lesion gets further away from the fovea. And that's why we were able to demonstrate this. The other thing that's notable is we had a really big trial looking at GA patients, the second largest study in GA, and we enrolled a really heterogeneous group of patients in this. So that's why we're able to demonstrate this more easily with our extra foveal patients. The reception was really positive and clinicians were really excited about this data.
spk16: Okay, I guess to just follow up on that point, Would that mean that you might want to target a different population in the four categories that you had mentioned? So maybe those that do have lesions that are further away from the center and just really be able to get the maximum benefit for those patients?
spk01: Well, again, Annabelle, if the benefit to the patient's focus is only on visually but we know for a fact that many patients who have foveal involvement at the start of the study, so-called sub-foveal patients, also will benefit from slowing down photoreceptor cell loss. So, you know, that is something that we clearly established and studied in our 1,200 patients that we studied in Derby and Oaks.
spk16: Okay, great. Thank you. Thank you.
spk02: Thank you. One moment for our next question. This question comes in the line of Joseph Stringer of Needham & Company. Your line is now open.
spk09: Hi, thanks for taking our questions. Two quick ones from us. Just curious if you can walk us through the immediate impact on both demand and sales when the permanent J code becomes available at the start of 4Q this year. And then on growth to net, knowing you're not guiding for it, but you, I guess you sort of guide for a normal range, but do you expect this to remain relatively constant as you progress through the launch?
spk12: Hey, Joey. I had a hard time hearing your first question, but I think it was about permanent J-code. So a few things about that is obviously a permanent J-code gives physicians and guarantees that confidence of getting reimbursed in a timely manner. So I do think that that will have a nice impact for us as we get to that stage of the launch in October. At the moment, obviously, we're working claim by claim and working for reimbursement claims. And one thing that I think is probably good for us to know, and you guys to know, is since launch, as of today as well, our understanding is that there have been more than 50 paid claims. So obviously, the permanent J code has a real solid impact for us as we get there in October, but We're doing pretty well to make sure that we're working through claim by claim. Now, the spin side to that is that the majority of the challenges we've seen tend to be basically process-related. And we also anticipate that that will smooth as we get over time. This is the first time some of these payers are seeing these GA patients come through their system. And it's manually done during the temporary JCOPE period. So that will improve post-impermanent JCOPE. Considering I didn't hear your question, I'm hoping I answered it.
spk05: Yeah, and I can answer the gross to net question. Did he answer your first part?
spk17: Oh, yes.
spk05: Very helpful. Thank you. So on gross to net, you know, we won't be guiding on gross to net, and it will change a little bit over time. What we're willing to say is that it's within pharmaceutical margins, which you can, or it typical pharmaceutical gross to net, which is in the 10% to 20% range, and I realize that's very wide. In our 10Q, we do add additional disclosure that we haven't in the past, but it does blend Empaveli and Cyphovri, and we give, you know, detail on chargebacks, discounts and fees, government and other rebates, and also returns on a year-to-date basis. So you can get a sense on a blended basis what that looks like, but we're not going to break it up by individual product.
spk09: Great, thanks for taking our questions.
spk17: Thank you, Joey.
spk02: Thank you. One moment for our next question. This question comes from the line of Douglas Tao with HC Wainwright. Your line is now open.
spk03: Hi, good afternoon, and thanks for taking the questions. Adam, you've spoken a bit about seeing demand from sort of smaller individual practices versus the PE-backed ones. Could you maybe provide a little more color in terms of what you think that means and ultimately how it will play out across both of those different practice sets? Thank you. And congrats on all the progress.
spk12: Thank you so much, Douglas. So, yeah, so actually I see it as a really strong leading indicator for us that we're seeing usage across the board of retina practices. So those who are private equity backed and have a, you know, a different process potentially on how they order and use Cyphovry. But the majority is coming from, you know, independent retina practices all across the U.S. And as I said before, a metric for me as a commercial guy, I'm thrilled that each one of our sales territories has had commercial sales. So for me, this is a sign of demand that we're not just getting the initial PE-backed usage. We're also working appropriately with those retina centers and independent retina centers to work through to get patients on the drug. So I can only see that progressing as we get broader within our target list and we continue to drive repeat prescription, et cetera. So I think it's a really strong sign across the board. So it's a great metric for us.
spk03: Okay, great. And if I can just a quick follow-up. In terms of samples, do doctors need to request samples for an individual patient, or are doctors able to keep samples just around in their offices?
spk12: Yeah, great question. So, yes, doctors need to request samples, but they don't need to request them for individual patients. So, they can request samples and then use them as they appropriately see fit.
spk03: Okay, great.
spk17: Thank you so much.
spk02: Thank you. I would now like to turn the call back to Cedric Francois for closing remarks.
spk01: Thank you so much. And in closing, thank you all for joining us today. We are around later today and tomorrow. If you have any additional questions, feel free to reach out to Meredith. This was a great start to the year for us, and we look forward to sharing more in the months to come. Thank you.
spk02: Thank you for your participation in today's conference. This does conclude the program and you may now disconnect.

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