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spk16: Good morning, ladies and gentlemen. Thank you for standing by, and welcome to APILIS Pharmaceutical's second quarter 2024 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 will need to press star 1-1 on your telephone. You will then hear an automated message advising you your hand is raised. To withdraw your question, please press star 1-1 again. Please be advised that today's conference is being recorded. I would now like to hand the conference over to Meredith Kaya, Senior Vice President, Investor Relations and Strategic Finance. Please go ahead.
spk17: Good morning, and thank you for joining us to discuss Appellus' second quarter 2024 financial results. With me on the call are Co-Founder and Chief Executive Officer, Dr. Cedric Francois, Chief Operating Officer, Adam Townsend, Chief Medical Officer, Dr. Caroline Baumel, and Chief Financial Officer Tim Sullivan. Before we begin, let me 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 actual results may differ materially. I encourage you to consult the risk factors discussed in our SEC filings for additional detail. Now, I'll turn the call over to Cedric.
spk10: Thank you, Meredith, and thank you all for joining us this morning. We are in a unique position today with one and the potential for two blockbuster drugs in the market, Cyphovri and Mpavini, both of which are making a meaningful difference for patients. The past six months have been a period of continued progress and execution by the Apelis team, but we recognize that there are questions around the competitive landscape for Cyphovri. Given this, I wanted to share some of my thoughts. Cyphovir is the market leader in a category with only two available drugs, one and a half million highly motivated patients, and a long runway for continued growth. That said, there has been a lot of focus on near-term dynamics. Our competitor has recently had tailwinds driven by factors such as its new J-code. They had every incentive to drive the amount in new patient starts as much as possible, and yet we saw approximately half of new patients choose Cyphovry. Following last month's successful ASRS meeting, we believe Cyphovry's clinical profile is being viewed favorably by physicians and will drive more growth in new patient starts over time. The Cyphovry launch has been one of the best launches in recent history, generating over half a billion dollars in sales in its first six quarters and achieving double-digit percentage growth every single quarter. More than 330,000 Sifovir injections are estimated to have been administered to patients, and this strong growth is continuing into the second half of the year. The GA market is growing significantly, and Sifovir has only scratched the surface of its long-term potential. Importantly, the recent ASRS meeting was a strategic turning point for us where our focus and our discussions shifted to Cyphovry's strong and differentiated efficacy profile. We have multiple analyses supporting the efficacy of Cyphovry, and retina doctors are enthusiastic about the totality of these data. The favorable benefit-risk profile of Cyphovry is becoming clearer to physicians with some key takeaways. One, Both monthly and every other month's Cyphovry treatment showed a better efficacy profile than the competitor among patients with non-sub-povial GA at both 12 and 24 months, as detailed in the matching-adjusted indirect comparison post-hoc analysis presented. Note that no head-to-head clinical trials have been performed. Two, Cyphovry is clinically proven to offer flexible dosing from day one, Every other month's treatment with cyphobre provides an even safer and more cost-effective treatment while maintaining its strong efficacy. And three, regarding safety, vasculitis is rare and appears to be a first injection phenomenon. The estimated rate has remained stable at 1 in 4,000 per first injection. During the podium presentation at ASRS, the REST Committee confirmed this estimated rate and agreed that it appears to be only on the first injection. After this meeting, we continue to believe that we are well positioned to continue growth and further cement our market leadership in GA for many years to come. Our singular focus is to ensure that every GA patient who needs treatment has access to Cyphovri. This is how we expect Cyphovri to continue on its path of becoming a multi-billion dollar drug. As for the European GA opportunity, we are focused on the CHMP reexamination process and are encouraged by the progress we made throughout the initial review. This was not an unexpected outcome, given that the process was reset back to day 180 of the initial review and therefore led by the original rapporteurs. We were encouraged to learn that in this recent opinion, multiple CHMP members disagreed with the negative opinion. Additionally, the external advisory experts were aligned on micro-parametry as the best available functional measure of GA. We are humbled by the broad support shown by the European retina community, and while we remain conservative in our expectations for the reexamination, we believe we are well-positioned heading into the appeal. Two new rapporteurs were recently designated, and we continue to expect the final decision to be issued in the fourth quarter of 2024. Moving to Empaveli, which continues to elevate the standard of care for patients with PNH. Empaveli generated $24.5 million in product sales in the second quarter. We continue to believe that patients on Empaveli are experiencing substantial benefits as demonstrated by its 97% compliance rate. Importantly, we are exploring its potential to expand into new indications and become a best-in-class treatment option for additional high unmet need areas. The upcoming Phase III Valiant stop-line readout in C3G and primary ICMP-GN is the next milestone in this process, and we expect to present these data later this month. If the data are positive, we plan to submit a supplemental NDA to the FDA for approval. Regarding the pipeline, we are advancing multiple earlier stage development programs, leveraging our core expertise in complement science to fuel the next phase of value creation for attendees. We look forward to sharing our progress at an upcoming investor day towards the end of this year. And finally, from a financial perspective, we are benefiting from the growing product revenue generated by Cyphovry and Empavedi and have actively taken steps to strengthen our balance sheet. We now have a clear line of sight to positive cash flow, allowing us to invest in future growth without having to rely on the capital markets. Before I turn it over to Adam to discuss our commercial activities, I will close by saying thank you to the patients and physicians who motivate us to develop and bring important treatments to market, and to the Apedis team who have shown unbelievable commitment and perseverance in getting these important medicines to patients, and to our shareholders, many of whom have stood with us through these dynamic periods and provided unwavering support to us over the years. With that, I will now turn it over to Adam.
spk13: Thanks, Cedric, and good morning, everyone. I will begin with Cyphovry. With revenue of about $155 million, sales growth remains strong at more than 12% quarter over quarter. In the second year of a product's launch, quarterly growth rates at these levels are a strong indicator of longer-term demand. We delivered over 79,000 commercial doses and approximately 5,000 samples of Slyfovir in the second quarter. Demand continued to accelerate, with June being our highest demand month since launch through the second quarter. We are particularly pleased to see the continued progress across the many factors driving growth, including new patient demand and a broadening prescriber base. Cedric mentioned some of the competitive dynamics, which I know is on everyone's mind. So let's start there. Our competitor had recent tailwinds driven by factors such as obtaining its new J-code. And so it is expected that they would see their proportion of new patient share accelerate. We also saw an acceleration when Sifovir's J-code went into effect last October. However, We do not believe this is indicative of longer-term market dynamics. We have taken the long view on contracting, as we believe this is a large and growing market and believe that discounting too aggressively now is unsustainable and will lead to price degradation over time. We are also executing our strategic plan in the field to reinforce SIFOBRI's benefit-risk profile. Sifo-V remains the number one chosen treatment for GA with approximately 75% of the treated market as defined by the total number of patients treated. We believe Sifo-V's position as the market leader will continue to be driven by its differentiated efficacy profile and flexible dosing. Importantly, we are also focused on maintaining market leadership whilst growing the overall GA category. we are still in the beginning stages. Our estimate based on claims data is that about 13% of GA patients who have been diagnosed and are managed by an eye care professional are currently being treated. In addition, only a small portion of newly diagnosed and treated patients are referrals, meaning that most patients currently receiving treatment were already being seen by a retina specialist. This suggests that the majority of GA patients have not yet been diagnosed or referred to retina specialists, reinforcing that we have only scratched the surface of the large opportunity for syphovry. As I mentioned on our last earnings call, we are now executing the next phase of our commercial and medical strategy. After the ASRS meeting in 2023, we developed a two-phase strategic plan with a two-year timeline. Phase one was focused on being transparent and educating the retina community about everything we were learning at the time around safety. This past quarter, we shifted to phase two of the strategy, which is focused on strengthening our leadership in this growing market. More than 2,100 sites of care have ordered syphovere. We are now on our front foot. expanding the number of new physicians using syphovere, deepening our relationships with existing syphovere users, establishing strong payer access and reimbursement, and increasing awareness and education for patients. With physicians, we are communicating a clean and simple efficacy message, highlighting syphovere's increasing effects over time, which is critical given that GA is a chronic disease. We are also sharing the micro-perimetry data from the Gale Extension Study, the only data for an approved GA treatment that demonstrates a visual function benefit in a pre-specified endpoint. This allows for a productive benefit-risk discussion with the every-other-month dosing option having a dramatically positive impact for patients, doctors, and payers. We had a successful ASRS meeting a few weeks ago our first big retina meeting leading with these messages, and look forward to the upcoming four congresses. We are also continuing to broaden our reach to more retina specialists, as well as other referring eye care providers who see tens of thousands of GA patients. Reaching these physicians and educating them on the referral process are key to developing the GA market. With Payers, we have secured unprecedented and broad coverage for patients choosing Sifovri. We're thrilled to share that two large national pharmacy benefit managers have recently made Sifovri the only preferred treatment on their commercial formularies. As the preferred product, this means that the new patients with commercial insurance will have full access to Sifovri as the first-line treatment and an exception process will have to be undertaken for non-preferred or disadvantaged products. While payers have several considerations in making such decisions, we believe these decisions were driven by Siphobry's compelling value proposition, highlighting its robust efficacy with increasing effects over time and both monthly and, more importantly, every other month dosing. These two PBM decisions are important milestones, demonstrating Payer's strong belief in syphobry's clinical and economic value proposition, as ensuring broad coverage and seamless reimbursement is critical for retina specialists. And with patients, we've launched the first phase of our branded DTC campaign in the spring, which is focused on encouraging patients to talk to their physicians about GA treatment with syphobry. We're excited to launch phase two of our branded DTC campaign, extending our relationship with the beloved Henry Winkler in the fourth quarter. This is a very large market, and we will be methodical in executing this next phase in order to set ourselves up for the long term. We will continue to execute flawlessly and be focused on getting more doctors, patients, and payers to understand the efficacy and the benefits that the leading GA drug can deliver. Now, let me shift to Emper Valley. In the second quarter, Emper Valley generated approximately $24.5 million in U.S. net product sales. The positive trends across the key leading indicators for the PNH patient population continue into 2024. Specifically, compliance rates remain high at 97%, and we continue to have a very strong safety profile. As we previously said, with the availability of an oral treatment for PNH, we are facing a more competitive market and expect sales to be flat at least through the next 6 to 12 months. We continue to have new patients starting in Povelli treatment, but this has been offset by some patients switching to an oral. Finally, I will echo Cedric's enthusiasm regarding the opportunity to potentially expand Empoveli into C3G and ICMPGM. This market is approximately three times larger than the PNH market, and there are no available treatments. If Empoveli is approved in these indications, we are confident that we can leverage much of our existing infrastructure to rapidly reach nephrologists and deliver Empaveli to the thousands of patients suffering from these diseases. With that, I will now turn the call over to Caroline. Caroline?
spk02: Thanks, Adam, and good morning, everyone. We are looking forward to sharing the VALIANT data later this month. I'll talk more about this opportunity in a minute. I will first talk about Sifovir, as our team was recently at the ASRS meeting in Stockholm where we had a significant presence with five oral presentations, including a late-breaking abstract on visual function from Gale. We are particularly excited by these visual function data, as this was the first time a geographic atrophy treatment had demonstrated a visual function benefit on a pre-specified analysis. Results showed that with respect to the micropermitory endpoint, Patients treated with pegcetacopelin monthly or every other month developed fewer new scotomatous points over 36 months compared to patients from the sham crossover group. Scotomatous points measure the areas of the retina that have lost all light sensitivity and therefore are no longer functioning. These results add to the largest body of evidence for a geographic atrophy treatment and reinforce the unprecedented effects shown by Sifovir to both meaningfully slow geographic atrophy lesion growth, and by doing so, preserve visual function. ASRS is one of the most important retina meetings of the year, and we had the opportunity to engage with many members of the retina community. This was a highly successful meeting for Sifovir, and we heard repeatedly from doctors about its differentiated benefits. We look forward to continuing to engage with this community at upcoming meetings and to share the ongoing progress of Sifovir in patients with geographic atrophy. Moving to Empaveli, later this month, we expect to share top-line results from our Phase III Valiant Study of Pegcetocoplin in people living with C3G and IC-MPGN. two rare and debilitating kidney diseases caused by uncontrolled complement activation and breakdown of C3. Patients are usually diagnosed in adolescence and about 50% advance to end stage kidney failure in five to 10 years. Treatment options are generally a kidney transplant or lifelong dialysis, neither of which are curative. In fact, Nearly 90% of transplant patients experience disease recurrence, and about half of them end up losing their transplanted organ. The Phase III VALIANT study enrolled 124 patients with either C3G or primary IC MPGN. This is the largest single trial conducted in these populations. and the only phase three study to enroll a broad population inclusive of adolescent and adult patients with native and post-transplant forms of disease. The primary endpoint of the VALIANT trial is a log-transformed ratio of urine protein to creatinine ratio, or UPCR, a key marker of disease progression in all patients at week 26 compared to baseline. We view success in this trial as the achievement of a statistically significant response to the primary endpoint, as well as positive effects in some of the additional secondary endpoints. Physicians have shared that this would be clinically meaningful for these patients. If VALIANT is positive, we plan to submit the supplemental NDA to the FDA for approval. Following the completion of the VALIANT study, patients were given the option to enroll into the VALE long-term extension study. We were highly encouraged to see that 100% of the patients who have already completed VALIANT have now enrolled into VALE. Beyond the VALIANT study, we are continuing to advance our earlier stage pipeline, such as our C3 siRNA that is currently in phase one development and our BEAM collaboration. Like Cedric said, we are excited to share more details about our pipeline programs with you at an investor day later this year. I will now turn the call over to Tim for a review of the financials. Tim?
spk09: Thank you, Caroline. I will now provide an overview of our financials and some comments on our debt refinancing with 6th Street. Additional details are available in the press release that we issued earlier this morning. Total revenue for the second quarter 2024 was approximately $200 million, including $155 million in SIPOVRI and $24.5 million in EMPA Valley U.S. net product revenue. This compares with $95 million in total revenue in the second quarter of 2023. Turning to the rest of the P&L, for the second quarter, cost of sales was $23 million, R&D expenses were $78 million, SG&A expenses were $128 million, and we reported a net loss of $38 million. As I previously stated, we are realizing efficiencies this year related to our restructuring in 2023 and continue to expect our total operating expenses in 2024, inclusive of R&D and SG&A expenses, to be less than our total expenses in 2023. This year, we've been focused on strengthening our balance sheet. These efforts ultimately resulted in a strategic, non-dilutive refinancing collaboration with 6th Street that we announced in May. The deal allowed us to prepay our SFJ debt at a significant discount and to free up substantial cash flow. A quick look at the terms reveals how favorable this deal was. First, this debt facility provides us with up to $475 million, of which $375 million became available immediately upon closing. We can access the remaining $100 million at our option over time. Importantly, this deal was debt neutral to Apellis. We replaced $366 million in payments due to SFJ over the next few years with $375 million from 6th Street. The principal repayment is pushed out to May 2030 when Sifo-V revenues are expected to be closer to peak. Our payments are interest only until then. This deal also substantially improves our liquidity and provides flexibility to access at least $200 million in incremental non-dilutive capital as we continue to invest in profitable growth. And it includes a record low credit spread. The overall terms were some of the best in biotech seen in recent history. In aggregate, since the beginning of the year, we have unlocked over $475 million in non-dilutive capital, including $100 million from the cap call unwind announced in the first quarter. Plus, we have the flexibility to bring in $100 million for an accounts receivable line, which can be increased to $200 million upon the achievement of certain milestones, and $100 million more from Sixth Street, so a total of $775 million in non-dilutive financial flexibility. This, combined with the $360 million in cash and cash equivalents that we had at the end of June 30, 2024, puts us in a strong financial position where we are on a path to becoming cash flow positive and no longer having to rely on the capital markets to fund the business. Importantly, our ability to begin generating cash is possible in both the EU and non-EU scenarios. While we believe the opportunity in Europe is significant, the ramp to peak sales is much longer, and so the main source of profitability in the near term remains growth in the U.S. I will now hand the call back over to Cedric for closing remarks. Cedric?
spk10: Thanks, Tim. We've had a very strong first half of the year. With two successful commercial products, a pipeline of innovative programs in development, and a strong financial position to support the business, I am more confident than ever in our ability to continue creating significant value for our patients and our shareholders. And we will now open the call for questions.
spk16: Thank you. As a reminder, to ask a question, please press star 1-1 on your telephone and wait for your name to be announced. To withdraw your question, please press star 11 again. We ask that you please limit yourself to one question and one follow-up. One moment while we compile our Q&A roster. Our first question is going to come from the line of John Miller with Evercore. Your line is open. Please go ahead.
spk07: Hi, guys. Thanks so much for taking the questions. I would love to start with – I'll start with this. Do you expect the share of new starts currently around that 50% mark to grow again post a successful ASRS? And then I guess the corollary to that is your guidance to cash flow positivity, you just mentioned, doesn't assume anything more than US GA launches, but does it assume more than the existing share of new starts in the U.S.? ?
spk11: Thank you so much, John. Great to hear you.
spk10: So, you know, that is, of course, the most important question, right? I mean, is the new start in the second quarter? As we have discussed, there were tailwinds for iSurvey. But as we now move forward, what really stands out and what is very encouraging to see is the very large market and the fact that Cyfovri is leading on efficacy, flexible dosing, and economic value. So as we move forward now, We plan to recapture the lead on those first injections and take advantage of this very large market with an important unmet need. Adam, do you want to add something?
spk13: Yes, thanks, Cedric. Hey, John. So, yeah, we're in phase two, and we're already encouraged by the growth and the demand we're seeing into July. We're on the front foot. We're talking about efficacy. We're talking about every other month dosing. These are huge differentiating factors for this great drug. we can see the future, and we can see that we will continue to be the number one GA drug in this market.
spk09: Tim? In terms of cash flow, our revenue was $199.7 million, and our cash OPEX, if you take out stock-based comp and depreciation, was just under that, so that was $199, a little bit less than that. So really on a total OPEX basis, on a cash basis, we are net neutral. So the differences right now are working capital and, of course, interest expense. So it really doesn't take much in terms of growth for us to become cash flow positive. We're not guiding to when that will happen. But given the size of the market and the growth in this market, I don't think that's something we worry about.
spk11: Great. Makes sense.
spk07: And I guess my follow-up would be your language on EU approval seems more positive now than it has in the past. You mentioned that you're well-positioned heading into this appeal, and I think that's a little bit more positive than the previous messaging we heard where all of our assumption was that this was not the base case. But how do you feel now versus how you felt last time you head into an appeal session? Do you really feel like the likelihood of an approval without further trials or without further resubmission is much higher now?
spk10: Thank you, John. So the expectation should remain the same. What is, of course, the one nice takeaway from the fact that the procedure was reset was the ability for us to introduce new data, and that includes the pre-specified endpoint function, which is, of course, something really important. encouraging, and really speaks to the appeal of this drug to patients. So, again, in terms of expectations, that has not changed. You know, the process has gone according to plan. We've been disciplined, and we look forward to the to share what the results are.
spk04: Thanks so much.
spk16: Thank you, and one moment as we move on to our next question. And our next question is going to come from the line of Anupam Rama with JPM. Your line is open. Please go ahead.
spk18: Hey, guys. Thanks so much for taking the question. You guys noted that for Cyphery, June was your best month since launch. Maybe you could give us a little more color on what you were seeing on a month-by-month basis in the quarter. You know, was the ISRV sort of JCODE impact more like first half of the quarter dynamic and then you saw re-acceleration of SIFO regrowth? Or how do we think about like what the dynamics were within quarter? Thanks so much.
spk10: Thank you so much. I will hand it over to Adam, but I think again what stands out here and what we're super excited about is how large this market is, the fact that it's growing. The fact that iZervate does well in a duopoly that will be here for a long time, and us having a drug that is meaningfully differentiated on efficacy and dosing flexibility, that is really what we are focused on. But Adam, you may want to add something.
spk13: Yeah. Hey, Adam Pan. So yes, June was the highest month of the quarter and also the highest month launch date. Across multiple metrics, we saw that Q2 was a very successful quarter for us. across multiple months, right? We continue to grow accounts, now getting to 2,100 sites of care. We saw double-digit growth for the quarter. We're fully into phase two of our plan, and I think some of the initial steps of that happening in June is what we can witness there, right? Talking about efficacy, talking about flexible dose, and I think that's what we're really pushing hard as we now move to the next quarter.
spk11: Thanks so much for taking our question. Thank you.
spk16: Thank you. And one moment as we move on to our next question. And our next question comes from the line of Sylvain Richard with Goldman Sachs. Your line is open. Please go ahead.
spk20: Hi, this is Srinath Rao for Sylvain. Thank you so much for taking our question. So on the competitive dynamics, what are the factors which are driving the competitive dynamics
spk10: and physician dynamics in the ga market following the permanent j code for eyes away and could you speak to the market share that you're seeing at this point and how you expect that to evolve over the near term thank you so much for that question so we are the market leader we plan on continuing to be the market leader and that confidence is based on stability around the safety which was really important and where srs was a real turning point for us, right, was for those that were there, it was a quiet meeting on that front, and the discussion very much shifted towards the efficacy profile. And there, the majority of doctors clearly see the differentiation of cyphovry versus the competition. So, as we now move forward, the focal point will more and more become efficacy, the differentiation, the long-term data, the mass amount of data that we have with cyphovry, and then the real and important benefit of every other month dosing. So the convenience that that offers to patients, also the fact that half the number of intravitreal injections is twice as safe as monthly injections, all of these things are going to come more into focus. Adam, if you want to add something.
spk13: Sure. Yeah. So obviously, if you go back to RJ code, we also noticed tailwinds when we had RJ code. It unlocked certain new accounts. So the competitor had some tailwinds, and even with those tailwinds, we maintained approximately 50% of new starts and market leadership at 75% of the total market. That is down, as Cedric said, to a real successful execution of phase two of our strategic plan, plus some positive comments moving forward from ASRS. Now, you also asked about market share. So we track market share based on vials going into physicians and then being injected into patients. And so we think that's the most robust way of measuring market share, and we had a 75% market share. Now, as this market grows, We will continue to push incredibly hard on our efficacy message, our dose inconvenience, and the economic value. And we think that that will maintain our leadership movement.
spk20: Really helpful. Thank you.
spk16: Thank you. Thank you. And one moment as we move on to our next question. And our next question comes from the line of Yigael Notramovitz with Citigroup. Your line is open. Please go ahead.
spk04: Hi, great. Thank you very much for taking the questions. Shifting over to PTG and ICMPTN. I just wanted to get your thoughts on how you expect the position types for the Copeland in this market, assuming valiant is positive, and what do you think we need to show on proteinuria, as well as some of the other secondary endpoints that Caroline mentioned to be competitive with the emerging oral options?
spk10: Okay, yeah, sorry, we had a hard time hearing you here. Tim, who has excellent hearing, translated for me. So, look, we are very excited about the opportunity in C3G and ICMP-Gen, as you know. This is something that has been a little bit below the radar screen of most, but a really large and important opportunity for us. We have seen the results from the NOBL study, where we have the histopath data, which is really testing class ever seen within this disease. We also have, you know, already, while this drug is not on the market yet, seen the excitement around science for this drug. And we have seen in the NOBL study approximately 50% reductions in proteinuria. So, you know, that is, of course, the goal for us is to meet statistical significance on the primary endpoint and then to really pay attention to the transgender population. So, yeah, I hope that answers your question.
spk04: No, that's helpful. And then I guess another question, in terms of the design and value, we are combining C3G and ICMPGN into one study. Obviously, the competitor is doing separate studies for both indications. Do you see that as being a a significant difference in terms of how physicians will interpret and implement the data when both drugs are approved?
spk10: Yeah, that will depend on the data, right? So I think you bring up a very important point, which is that the way in which the study reads out should be viewed in the context of, of course, what we have seen with FabAlta. We decided to include in one study both C3G and ICMPGN with the hope that the data would be good enough for both to find their way into our labels. So we're going to see if that's the case or not. And we're going to see how the data stacks up against what has already been disclosed by Novartis in the past months. Great. Thank you. Thank you.
spk16: Thank you. And one moment as we move on to our next question. And our next question is going to come from the line of Steve Seedhouse with Raymond James. Your line is open. Please go ahead.
spk12: Thank you. Good morning. Thanks for the update. First question, I just, regarding a new line item on the balance sheet for long-term inventory, a $23 million entry, has there been any change to the expected sales trajectory in the next 12 months versus prior? Are you anticipating that entry will be gone in subsequent quarters or is it going to grow? And then also, what is the shelf life of the raw materials, I guess, that comprise that entry?
spk09: Yeah, thanks, Steve. So that entry was put in place because we have to do our ordering for our inventory long in advance, and we had planned for the potential success of ALS. There's also a couple of other factors, which include the delay in the EU for cypovery and also our expected ordering from SOVI. So we had to plan for all that well in advance. And so much of that, in fact, most of it has to do with infidelity. We don't know exactly how long that line item will last there, but most of that inventory has a shelf life of three years or more. So we just put that in place because of the dynamics we talked about, but it's primarily info-valued.
spk12: Okay. Good to know. And then just on the dynamic of patients maybe switching between iZervay and Cyphovrii, Do you have good visibility into both directions of switching there? And has it been, if so, has it been sort of a net positive, net negative, or net neutral in terms of unique patients on either drug? Thanks.
spk13: Hey, Steve, it's Adam. So, yes, we have some visibility to that. Now, obviously, with all analysis that we can do, it's only a subset of the total market. So, obviously, last year, we did see some switching from Cypovery to Isovay. We saw one or two accounts switch the majority of their patients. And what we have seen moving forward is we've actually seen some switching from Isovay to come back to Cypovery. And our assumption there is that's based on the efficacy and the flexible dosing of this drug. Switching tends to be a very small piece of the market, and it goes both ways based on our data set. As we look forward into Q3 and beyond, right, we're really, really encouraged by all of the metrics we're seeing about strong demand across multiple metrics. That includes switching as a piece of it, a small piece of it. That includes new starts and our plan to execute everything to push new starts. It includes more physicians writing Cyphovry for the first time and increasing the number of accounts that are using Cyphovry. We're really, really positive on what we're seeing so far, and we think a lot of that's down to this strong efficacy, the leading efficacy, flexible doses, and economic balance. Hopefully, Steve, that answers your question.
spk11: Yes, thanks so much, Adam. Thank you very much.
spk16: Thank you, and one moment as we move on to our next question. And our next question is going to come from the line of Colleen Cousy with Baird. Your line is open. Please go ahead.
spk15: Colleen Cousy Great. Thanks. Good morning, and thanks for taking our questions. Can you provide any thoughts on when you might provide revenue guidance for SIFO REITs?
spk09: Tim Stenzel Sure. Thank you. So, obviously, we're not providing it for the remainder of this year, and it's something we'll reconsider for next year, but we're not guiding on one guide yet.
spk15: Thank you. And then for the EU review, I think you said the rapporteurs have been selected. Can you provide any commentary on the background of the new rapporteurs and if either of them were a dissenting voter from the most recent review?
spk10: Thank you so much, Colleen. So we don't provide details on that. As mentioned, we consider the odds of success to have remained stable, the process to have gone very much in line with what we had expected, and hopefully In the fourth quarter, we'll be able to come back with positive news.
spk15: Understood. Thanks for taking our questions.
spk10: Thank you, Colleen.
spk16: Thank you. And one moment as we move on to our next question. And our next question is going to come from the line, as Phil may do, with TD Cowan. Your line is open. Please go ahead.
spk03: Morning. Thanks for taking our questions on the competitive environment. First, I'm a promoter in Japan. Can you talk a little bit more about what you're seeing from your competitors in terms of the cap and a little bit more about what else is going to be happening? And second, the dynamics of the competition, what do you think the position in center level overall are students becoming eye survey versus eye focus positions, positions using both centers versus the other, or are they using both?
spk10: Hey, Phil, I don't know if it's our line or yours, but we have a very hard time hearing your question. Sorry, let me try again.
spk03: Yeah, so first on discounting, what are you seeing in the marketplace on discounting, and what is Apellas' own strategy on discounting? And then second, on competition, can you talk about on the physician center level, Are centers choosing one or the other, or are they going patient by patient in using iZervate versus SecoBridge? Thanks.
spk11: Thank you so much. Adam, do you want to take that?
spk13: Yeah. Hey, Bill. Thanks for repeating the question. So contracting is obviously a standard process in this market, and we're taking a really strategic and thoughtful view on how we contract in this market. This is a large and growing market, and we've only just scratched the surface of moving patients into the market. So if you look forward to how big this market can possibly be, we want to maintain as much value as is possible. So we've been incredibly thoughtful on contracting. Then to your second part of your question. So at an account level, we have seen that there are many SIFO ovary advocates and fans. And these physicians are choosing SIFO ovary for its leading efficacy, flexible dosing, its now well-documented safety profile, and the robust real-world evidence. And that comes consistently when we interact with physicians at conferences and various other interactions too. Now, no surprise, there are always some Competitor physicians also, who tend to be choosing the competitor for its safety profile. One thing we have noticed, and I don't know if Caroline wants to comment afterwards, is a lot of physicians will have a discussion about cyphobry, for example, with their patient and explain the efficacy profile and the flexible testing. And some physicians will have the same conversation on either. So the patient voice is also important in this discussion and we truly believe that efficacy will drive patients to want to choose something. Caroline, anything you want to add?
spk02: Thank you. Hi, Phil. I think when it comes to physician use, we just had an ad board yesterday and speaking with my colleagues at ASRS, they're very driven to have less than monthly dosing, which is is consistent with the high efficacy. And they're really also driven by our data that goes into the third year of use, that patients have completed the Gale study, some patients with over five years of continuous use of Cypovery. So to them, the most important thing is to give the maximum efficacy with the least burden for patients.
spk03: That's helpful. Thank you.
spk16: Thank you, and one moment as we move on to our next question. Our next question comes from the line of Akesh Tiwari with Jefferies. Your line is open. Please go ahead.
spk21: Hey, this is Amy on . Thanks so much for taking our question. So, you've alluded to a safety update second half of this year. Just wanted to get a sense of what that could entail. Also, given iZervay has half the amount of PEG and a shorter half-life compared to Cyvovery, Are you working with ASRS or other doctors to run studies looking at dose titration or spaced out dosing regimens for Cyphovir? And when can we get an update on that?
spk10: Thank you so much for that question. So first of all, the safety is now very clear and well established. So what was really important for us was at ASRS that the ASRS REST Committee agreed with APEDIS on the rarity of these events. one in 4,000 on the first injection, and the fact that this is primarily a first injection phenomenon, right? So those are important facts. And of course, then you place it in the broader context of the safety, where Cyphovir stacks up very well against iZerva, specifically also because of that every other month dosing that is available. So, you know, based on an enormous denominator of 330,000 injections, we know very well what the safety profile is. I don't think there's going to be much more discussion around that. What we will talk a lot about now is what the efficacy really looks like. And I think that is where the discussion is going to go. What was really gratifying to see coming out of ASRS is that everything is becoming more quiet and more reasoned within this field. So only 13% of patients with GA right now have been treated. These patients are desperate for treatment. They are going blind. Understanding the safety profile and the efficacy that they get in return is really important and is going to drive the growth of this market for many years to come. So that is something that really stood out. In terms of mitigations, for something as rare as this event, you know, it is a question, what can you do? What should you do? It's, of course, you know, when it happened, it's not good, but, you know, Intravitreal injections carry a risk. Every time you do an intravitreal injection, there's a chance of 1 in 3 to the 5,000 of getting infections and osteomyelitis as well. That is normal with any type of drug. So this is really something that we're looking forward to. I don't know if Caroline wants to add something.
spk02: I think the retina community has really appreciated our transparency with this and our partnership. I mean, we are driven by science and we're driven by what's going to be best for patient care. And that is the continual feedback. And I will tell you that the community would have no problem giving different sort of feedback if that was indicated. So they're really pleased with this. And they're really excited to continue to work with us and develop more data for our patients to give them the best care.
spk10: And we're really feeling that momentum this quarter, right?
spk11: I mean, it's really, I think SRS was a real turning point for us.
spk16: Great. Thank you so much. Thank you, and one moment as we move on to our next question. And our next question is going to come from the line of Ellie Marie with UBS. Your line is open. Please go ahead. Hey, guys. Thanks for taking the question.
spk00: Just a quick one on SIFO-RAE and then a question on VALIANT. Sorry if I missed this before, but can you confirm if volumes were up in July versus June for SIFO-RAE? For Valiant, just how are you thinking about what's clinically meaningful in the pre- versus post-transplant setting? And then any difference in efficacy expected between these two settings? And just commercially, how you're thinking about the relative size of the population opportunity for PEG-SETA co-plan in the pre- versus post-transplant patients? Thanks.
spk10: Thank you so much. Adam, do you want to take this first?
spk13: Sure. Yes. So we're really thrilled with the strong growth because it's continuing into – July, and we expect it to continue for the rest of the quarter and onwards. We're seeing it across multiple metrics, and I think it's down a lot to flawless execution of phase two of our plan. We are now on the front foot, and we're pushing hard. So we're thrilled with what we're seeing into July. We expect that to continue. We're going to work hard to make sure.
spk10: And then as it relates to valiant, so pre- versus post-transplant. So as you may recall, Elite Forest, the The post-transplant segment is a very intriguing one because it's easy to take biopsies and to track on histopathology what your drug does in that population. It is also a population that was kind of deprioritized by our competitors, and it's one that we happily embrace because what is best for a transplanted kidney is best for kidneys with this disease, period. So this is really something that has many advantages for us to focus on. But on the other hand, should our data be really good and valiant, there is a real opportunity to differentiate from FabAlta. And, you know, in a disease as serious as C3G or ICMPGN, you know, efficacy is what will really, really matter more than convenience, right? Whether you take a pill or a subcutaneous, if you have a real differentiation on efficacy, that is what will stand out. I also want to point out, of course, we've always talked about the remarkable safety profile that we've seen in PNH and the other indications for Mpavedi. has been used that is on the market, combined with this extraordinary compliance rate of 97%. Empa-Veti, which has the same active ingredient as Cyphovri, is an amazing drug, and hopefully in Valiant we will see a new indication emerge for that drug.
spk16: Great, thanks. Thank you, and one moment as we move on to our next question. And our next question comes from the line of Annabelle Simonyi with Stifel. Your line is open. Please go ahead. Hi, all.
spk01: Thanks for taking my call. So, I guess in our channel checks, we're happy to find that consensus among these physicians we spoke to is generally in line with your comments that physicians give syphilis that edge on efficacy. I guess my question is how are they responding to the micro-perimetry data? Because it's not something that they typically do in their offices. How can they use that with their patients practically so they can show patients benefit over time and keep them motivated? And I ask that, I guess, for retention beyond that, say, 18 months, a two-year timeframe where patients may start dropping off. Do they have the tools right now? And are they starting to adopt some of these tools so they can demonstrate to their patients that this is working? Thanks.
spk10: Thank you, Annabelle. Adam is going to first answer the first question.
spk13: Thanks, Adam Bell. So I appreciate your comments on efficacy. We also did a recent piece of market research, and we noticed in our sentiment to our market research that our efficacy perception is increasing, and there's a gap between us and the competitor in our market research. So it seems to confirm what you said. I'll hand over to Caroline on microphone.
spk02: Thank you, Adam. Physicians are really excited about the microprimitary data. And in showing them, they see the trend in the microprimitary data that's followed over time and that it reaches this pre-specified endpoint. I think that most physicians realize that microprimitary in many ways is analogous to a visual field testing. And they appreciate that it shows a benefit in a clinical trial. But in the real world, they like to use OCT, which also has shown benefits using our AI algorithms combined with the University of Vienna. So I think the fact that we have this pre-specified endpoint, though, is very highly meaningful. And it will mostly be used to date in clinical studies, although some people are using microtermetry in the real world. In the real world, we can use imaging to show this to patients, and we have cases that we've shown to physicians. In fact, we showed one at ASRS where a patient in the observed fellow eye, the geographic atrophy grew three times as much compared to the treated eye. So cases like this are highly meaningful, and that was in Matt McCumber's video talk at ASRS.
spk16: Great. Thank you. Thank you. And one moment as we move on to our next question. Our next question is going to come from the line of Francois Brissebois with Oppenheimer. Your line is open. Please go ahead.
spk05: Hi. Thanks for the question here. So I was just wondering, so in terms of function we've discussed, but on convenience and the importance of that and the economic value, can you help us understand a little bit
spk10: from you know the convenience is that as advantages to the physician as it is to the patient i'm just trying to understand if convenience and economic value here have a correlation or or not thank you francois well there's three pieces to that question right there's the convenience to the patient convenience to the physician and then the convenience quite frankly to the payer so when we start with the convenience to the patient having every other month dosing available is really, really important. Our competitor, sure, there is some off-label use with every other month, but our competitor has only monthly. We're going to find out at the end of this year if they actually ever get every other month in their label. This is a huge point of differentiation that we will benefit meaningfully from should it end up the way we think. The advantage to physicians is of every other month is, again, the flexibility. And, you know, I'm going to let Caroline answer, like, her view on that, and then have Adam dive into the payer aspect of the cost, the value.
spk02: Well, certainly to realize the anatomic benefits of Cypovery, we've seen that every other month dosing is meaningful. And I think that with our flexible every 25 to 60 days in our label, patients can come every six to eight weeks and still realize these meaningful effects. And certainly in the U.S., physicians love to have that plus minus one to two weeks with their dosing. And it's more likely for patients to come in and complete this. We know that with monthly dosing from our anti-VEG experience, it's really very, very difficult to complete that, and patients will often drop out because they cannot maintain that. Adam?
spk13: Yeah, thanks. So, obviously, we're thrilled that some payers are starting to look at this category and selecting Siphovery as a preferred choice. So, this decision was basically made on its robust efficacy profile, and particularly the increasing effects over time And I think it's really basically simple, right? Cyphovir is efficacious with monthly and every other month doses. And this is good for patients and is economically supportive for the health plan. And I think that's going to be important for us as this market continues to grow and become bigger and bigger.
spk10: And, you know, context there is that the flexibility is everything, right? Some patients with aggressive lesions want to be dosed monthly. We have seen very clearly in Gail as well. But there are advantages to treating monthly, right? I mean, it is more intense from a dosing perspective, of course. But in terms of reducing the lesion growth, there is an advantage to monthly. So that flexibility, the huge amount of data that we have, both, you know, in its absolute, but also longitudinally over time, we have three years now, we will have more data coming. All of that's incredibly valuable.
spk05: Okay, and just lastly on the Valiant data, just because it's coming up very shortly here, you guys discussed in terms of success and expectation, you know, stat sig on the primary. But on the secondary, in terms of is this the positive trend on, you know, some secondary endpoints or all? And is this what the regulators need to see from conversations? They're just trying to understand more on the secondary endpoints importance here.
spk10: Yeah, the secondary endpoints, you know, need to trend supportive. of the primary endpoint. We have seen this with FabAlta, where none of the secondary endpoints were met. But where we believe there is still a path forward for FabAlta, they were specifically asked to submit the data at one year, as you may recall, after having the six-month primary endpoint. Those are all things. Secondary endpoints are more contextual, but very important to provide support to what we measure with the primary endpoint. area reductions.
spk16: Thank you. And one moment as we move on to our next question. Our next question comes from the line of Doug Oso with HC Wainwright. Your line is open. Please go ahead.
spk19: Hi, good morning. Thanks for taking the questions. I'm just curious, Adam, in terms of the patients that are now being treated, I think in the past you indicated that like 90% of them were already on the books of retina specialist. I'm just curious if that continues to be the case. And then in terms of the DTC work that you've done, for the most part, I think the Henry Winkler campaign has sort of been an unbranded campaign. Does there come a point where you might consider, now that you're quote on, you know, sort of in phase two, switch to a branded DTC effort to sort of focus on the competitive dynamics and the attributes of Cypher-3 versus Isurvei?
spk13: Yeah, thanks, Doug. So, yeah, this is obviously a large and growing market with 13% market penetration for the current approved therapies. And most of those patients, in fact, the vast majority of those patients were already on the books of retina specialists. So they're tapping into the patients that have GA that they were perhaps seeing that had other complications, for example. One thing, phase two of our plan is super critical, and DTC is also a part of it, is that we are going to educate ophthalmologists and optometrists on geographic atrophy as a disease. And once you start to educate those physicians, they will be able to potentially refer viable patients to retina specialists for treatment. We see this as a really big market, and actually facilitating that education is only going to help us So DTC, Doug, yes, Henry Winkler was diseased at education. It was incredibly well received by patients, but also by physicians. We did transition as part of phase two to branded DTC. So Henry was educating the world about go and get your eyes checked. And branded DTC is talking about syphobry and the benefits of the efficacy that syphobry can cause so that patients are educated on the disease. and then they can go and ask to have a conversation about . As we progress moving forward, we're going to push DTC with a real strong approach on actual cyphomery, and there's some exciting things happening with Henry moving forward.
spk19: Great. Thank you so much.
spk16: Thank you, and one moment as we move on to our next question. Our next question comes from the line of Brian Amann with Piper Sandler. Your line is open. Please go ahead.
spk08: Yeah. Hi, guys. Thanks for taking my question. Maybe if I could start with, you know, the competitive dynamic. Estella earlier today on their call, you know, stated that they're seeing eye survey capturing majority of new patients starts. Are you seeing similar trends from your treatment use market research data?
spk13: Yeah, so we are seeing through our data set, which is not market research. We use a data set that actually tracks vials into a physician site and then into a patient. So we believe in the robustness of this, but we could do market research, and I think you get some bias when you do market research, which you have to take into account. And with the headwinds the competitors had, we were still maintaining approximately 50% share of new starts. And I think that's really, really strong considering it was the quarter of their J code. So that's how we look at the data set. We believe 75% market share of total market is a very robust number. And we look to the future of how big this market can be and being the number one GA product in it.
spk08: Great. That's helpful in terms of data point. And then maybe if I could have a follow-up. So on the quarter, it seems commercial units grew about 10% quarter over quarter. If you take out samples, sales grew about 12% quarter over quarter. So is the remainder from lower gross to net in the quarter? And what should we expect for gross to net for the third quarter?
spk11: Sure. So gross to net
spk09: And obviously, we don't say exactly what gross net is. It did go up slightly this quarter, but was really well within the range of where it was last quarter.
spk11: And in terms of the files out, you know, those are the accurate numbers, and we don't guide the whole board on those. Great. Thanks for taking my questions.
spk16: Thank you. And one moment. And our last question is going to come from the line of Greg Suvanovich with Mizuho Securities. Your line is open. Please go ahead.
spk06: Okay, great. Thanks. Thank you for taking my question. I just wanted to follow up on earlier in the year comments around seasonality and how that impacted the first quarter in particular. And just wondering as you've got second quarter now behind you, if you can provide us any commentary on what you're expecting, if anything, around seasonality impacts in the third and fourth quarter, just as we think about modeling SIFOV revenue on a go-forward basis? Thanks.
spk13: Yeah, thanks for the question. So, obviously, seasonality is an important metric to measure here. Every time we go to a big retina conference like ASRS a couple of weeks ago, right, a large proportion of physicians are there. So, there are multiple retina meetings moving forward. where physicians will be out attending those conferences and learning about our efficacy data. Caroline, anything you want to add from your retina physician perspective?
spk02: That the retina physicians are really looking forward. We have some upcoming exciting presentations. And they want to offer patients a product that's going to be effective with increasing effects over time. So they are very motivated and looking forward to working with us on analyzing the data.
spk06: And just as a follow up, just anything on like purchasing patterns, you know, seasonally, third quarter versus fourth quarter? Bigger picture.
spk09: I don't think we've had enough experience yet to really say that, at least in our, you know, in terms of this market. Anti-vegetarianism isn't anything that stands out particularly. I mean, obviously you have August, and that can be a full month just because of vacations.
spk11: There's nothing really dramatic. Okay. All right. Thanks very much.
spk16: Thank you. And I'm sure, as I said, there's no further questions, and I would like to turn the conference back over to Cedric Francois for any further remarks.
spk10: Thank you, operator. Thank you, everyone, for joining us this morning. If you have any follow-up questions, please feel free to reach out to Meredith, and we look forward to hearing and speaking with many of you today. Thank you.
spk16: This concludes today's conference call. Thank you for participating, and you may now disconnect.
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