Apellis Pharmaceuticals, Inc.

Good morning, ladies and gentlemen. Thank you for standing by, and welcome to the Appellate Pharmaceuticals Third Quarter 2025 Earnings Conference Call. Please be advised that today's conference is being recorded. I would now like to turn the call over to Evel Straynoski, Head of Investor Relations. Please go ahead.

Good morning, and thank you for joining us to discuss Appellate's Third Quarter 2025 Financial Results. With me on the call are co-founder and Chief Executive Officer, Dr. Cedric Francois, Executive Vice President of Commercials, David Atchison, 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.

Thank you, Eva. Before diving into our third quarter results and portfolio progress, I want to briefly highlight the unmet need that Aperis set out to tackle and why we are uniquely positioned to address that challenge. Aperis is a commercial stage biotech company targeting the over-activation of the complement system an innate defense mechanism in the immune system that protects the body from acute infection and illness. However, when complement is chronically unregulated, there can be a devastating effect on one's health, driving a broad range of serious, often life-threatening diseases. Most approved complement targeted therapeutics inhibit at C5, a downstream protein in the complement cascade. By only blocking this target, T5 inhibitors do not affect the upstream activity that drives inflammation and tissue damage. Similarly, inhibitors of factor B act earlier in the cascade and narrowly, reducing alternative pathway amplification, but allowing classical and lectin pathway activity to persist, leaving some disease activity unchecked. Appendices science is founded on a simple but powerful idea, to address complement-driven diseases at their source by targeting C3, the central hub where all complement pathways converge. By doing this, we take a fundamentally different approach that enables comprehensive disease control at the root cause. For decades, the prevailing view was that C3 could not be effectively modulated because of its central role in immune defense. Apedis solved this challenge by engineering pexetacoplan, a first-in-class C3 inhibitor that controls overactive complement while preserving essential immune function. The result is both a technological feat in drug design and a transformative clinical advancement for patients. This vision is what sets Aperis apart. We have mastered our core technology and redefined complement therapeutics. The scientific advantage underpins our success to date. Having now translated decades of innovation into two approved medicines across four serious diseases, Aperis is a commercial stage leader with a truly differentiated C3 platform. Cyphovrine is the first-ever treatment for geographic atrophy, having shown robust efficacy in slowing disease progression in the broadest patient population. And Pavelli has demonstrated best-in-class hemoglobin improvement in PNH and the ability to completely clear C3 deposits from the kidney. Together, these achievements underscore our unprecedented clinical innovation, and strengthen Apelis' competitive edge in complement science. Turning now to our business results. The third quarter was a period of further progress where we continued to build on our strong performance. A key milestone was the FDA approval of Empaveli for the treatment of patients 12 years and older with C3 glomerulopathy or primary immune complex membranoproliferative glomerulonephritis, or ICMPGM. This approval expands the addressable market for Empaveli by approximately 5,000 patients and marks a breakthrough therapy that delivers meaningful results across the trifecta of key disease control measures, including proteinuria reduction, EGFR stabilization, and substantial clearance of C3 deposits. With a broad label in hand, We are well-positioned for launch in a space where physicians consistently note that efficacy will drive treatment decisions. David will share more launch progress shortly. Moving to cyphovarine. Geographic atrophy is a devastating disease that progressively and permanently robs patients of their vision. Unfortunately, in managing GA, many retina specialists have adopted a wait-and-see approach. despite Cyphovry's well-established clinical profile that demonstrated robust, sustained, and increasing benefits with every other month dosing. Because of this, only about 10% of patients diagnosed with GA are treated with complement inhibitors today. In the near term, we expect a period of steady, measured injection growth, with the next inflection in growth to be driven by new tools and targeted market education initiatives that we plan to bring to market over the next 12 to 18 months. We believe these initiatives will re-accelerate the adoption of complement treatments and grow the overall GA market. Overall, our focus remains on leveraging our expertise in complement-mediated diseases to positively affect the lives of people living with serious illnesses. With this in mind, We continue to maximize our market opportunities for MPaveli, drive expansion for Cyphovry, and advance our pipeline. I will now hand the call over to David for an update on our commercial activities. David?

Thank you, Cedric, and good morning, everyone. I'll start with MPaveli and the recent approval in C3G and primary ICMPGN. We are now two months into the launch, and I am very pleased with our progress so far. Feedback from the nephrology community has been outstanding and we are carrying that momentum into Q4. In the U.S., we estimate there are approximately 5,000 C3G and primary ICMPGN patients, notably Empaveli's broad label makes it the first and only treatment approved for a comprehensive list of patient populations, including adult patients with C3G, adult patients with ICMPGN, pediatric patients with C3G, primary ICMPGN patients age 12 years and older, and patients with post-transplant C3G disease recurrence. Empaveli is the only approved therapy for approximately two-thirds of this 5,000 patient population, and we believe it offers highly differentiated efficacy for the other third where patients have an alternative. Together, the broad label and the strong clinical data position the launch of Empaveli for the long-term success. For the first time, patients can be treated with a first-in-class C3 targeting therapy and the only complement therapy that has demonstrated its ability to preserve kidney function by controlling all three markers of these diseases, including proteinuria reduction, EGFR stabilization, and substantial clearance of C3 deposits. Infaveli is delivered through our compact, single-use, on-body auto-injector. Patients can self-administer in the comfort of their own home without ever seeing a needle. Early feedback from the market has been exceptionally positive, highlighting its ease of use and the convenience of the twice-weekly dosing. The PK profile of Empaveli allows patients the flexibility to take treatment on their own terms, avoiding twice-daily dosing required by the oral alternative. Ahead of the launch, we scaled our field-based teams to approximately 100 people, ensuring coverage of every U.S. nephrologist managing these patients. Our extensive pre-launch engagement with physicians and patient identification efforts have built a strong foundation for a successful rollout. As communicated in our approval call, the launch metric that we will be reporting early in launch is patient start forms. Through the end of September, we received 152 patient start forms for Empaveli. Included in this number are the approximately 50 patients from our Expanded Access Program, or EAP, who are in the process of converting over to commercial drug. We remain on track to have these EAP patients on commercial drug by the end of this year. As a reminder, it generally takes four to six weeks for a patient to start treatment. We see opportunities to potentially accelerate this timeframe as we gain more experience in our launch and as payer's policies are updated. During the quarter, we made meaningful inroads with high volume prescribers and are confident in the continued growth of adoption. Of the 20 most influential and high volume accounts in the space, 19 have a REM certified prescriber and the majority of these centers have submitted start forms. clear evidence that our launch efforts are translating into real-world adoption across priority accounts. On the access front, we are encouraged by payers' recognition of the value of Impaveli in C3G and primary ICMPGN and by the speed at which these patients are successfully gaining access. Furthermore, our dedicated Appellate Assist team is closely working with patients and prescribers to navigate the expected prior authorization requirements to minimize delays and support a smooth start to therapy. These have been incredibly encouraging early weeks for our rare disease launch, and we are excited by the strong engagement from both physicians and patients. We are learning a great deal about prescriber habits, and once physicians are educated on the differentiated profile of our therapy, they quickly become strong believers in its disease-modifying potential. We believe we have worked through most of the one-time wave of early adopters and EAP patients and expect to receive 225 cumulative start forms or more by the end of this year. Looking ahead, we are confident in the long-term growth potential of Defaveli as awareness deepens and patient access continues to expand. Moving on to Sifovri, we are encouraged to see continued market leadership with a total estimated injection growth of 4% during the quarter, in line with our expectations. Sifovri maintains its leading position, accounting for an estimated 52% of new patient starts during the third quarter, and more than 60% of the overall market. As commercialization matures, we've moved past the early adopter phase and expect steady, measured injection growth for the near term. Importantly, we believe that the long-term market opportunity remains significant with blockbuster potential. Today, only about 10% of patients who are diagnosed with GA are being treated, and specifically for retina specialists, on average, just one in five patients with GA in their practice are treated with a complement inhibitor. This leaves substantial room for growth by expanding the total number of prescribers and by increasing adoption within existing practices. To drive this opportunity forward, we are focusing on disease awareness and education, laying the groundwork for the next wave of growth through initiatives that include engaging with early career retina specialists who see a disproportionate number of new patients, enhancing education around the importance of early intervention and maintaining patients on treatment, and refining our messaging to better-equipped field teams in their outreach and discussions. I will now hand the call over to Caroline to share additional color on these initiatives and provide an update on our pipeline. Caroline?

Thanks, David. Let me start with syphovary and geographic atrophy. As the only approved drug that binds to C3, the central protein of the complement cascade, Sifovir potently inhibits the damaging downstream effects of complement overactivation, forming the basis of its strong clinical profile. Patients with GA are on an irreversible path to blindness. As Cedric and David mentioned, there is ample opportunity to advance the understanding of GA within the treatment community and to instill the urgency to treat patients early to save retina tissue. To support this, we are developing artificial intelligence tools that will help physicians gain a better understanding of what GA patients experience, as well as the benefit of treatment with Sifovir. We are also working to provide more convenient administration through the development of a pre-filled syringe. We believe that both of these key initiatives will broaden the prescriber universe within the overall GA market and drive higher utilization of Cypovery over time. Turning now to Mpivelli in C3G and primary IC MPGN. The treatment community's response to the recent approval has been incredibly positive, and we are confident that it will be the preferred treatment option for these patients. We're excited to share seven abstracts at next week's American Society of Nephrology meeting, further demonstrating Empaveli's profound and durable benefits and underscoring our commitment to the rare nephrology community. Building on this momentum, we are expanding Empaveli's development into two other rare kidney diseases, primary focal segmental glomerulosclerosis, or FSGS, and delayed graft function or DGF. Similar to C3G, FSGS is a rare kidney disease that progresses to kidney failure within 5 to 10 years for about half of patients. DGF is a complication in kidney transplantation that negatively affects the long-term survival of the kidney and the overall patient outcomes. The complement pathway plays a significant role in both diseases. and there are currently no FDA-approved therapies for either. We are well underway with our planning activities and expect to initiate pivotal trials in FSGF and DGF by the end of the year. With that, I'll now turn the call over to Tim for an update of the financials.

Thank you, Caroline. Total revenue for the third quarter was $459 million, including the $275 million upfront payment from SOBI in connection with the Aspa Valley Royalty Purchase Agreement. Cyphery net product revenue for the quarter was $151 million. We delivered approximately 101,000 doses of Cyphery in the quarter, including 86,000 commercial doses and 15,000 free goods doses. In line with our expectations, we saw 4% sequential growth in overall total injection demand during the third quarter, driven predominantly by free goods. While we are encouraged by the continued growth in total injections as a leading indicator of demand, we did see an approximate $15 million headwind to our reported revenue due to the elevated use of free goods, which was slightly higher than our expectations. Through the first three quarters of the year, we estimate that free drug has been a nearly $40 million headwind to syphilvery revenue. Looking ahead to the fourth quarter, we continue to expect modest syphilvery total injection growth within the low to mid single digit range. Turning to gross to net dynamics, Adjustments during the third quarter for syphilis remained within the low to mid 20% range, consistent with our guidance through 2025. As we move into Q4, we expect growth to net to trend slightly above the prior range. This reflects the normal stepwise pattern of growth to nets over time, with modest degradation and some quarter-to-quarter movement that's typical in the buy-and-go market. Importantly, this reflects expected dynamics rather than a structural shift. and we remain confident in our pricing and access position heading into 2026. From a channel perspective, we anticipate a modest channel build during the fourth quarter, consistent with seasonal patterns expected at year-end. That said, we continue to target stable inventory levels quarter over quarter, and we'll provide further commentary during our year-end update. Taken together, our current view is that the fourth quarter SIFOVERY revenue will be broadly in line with what we recorded in the third quarter. Looking beyond these short-term dynamics, as Cedric and Caroline mentioned, we have several compelling opportunities that are largely within our control to reinvigorate SIFOVERY's growth over the next 12 to 18 months. We remain confident in the meaningful long-term potential of SIFOVERY and look forward to updating you on our progress in bringing these initiatives to fruition. Moving now to Empaveli, total net product revenue across indications, which includes PNH, C3G, and primary ICMPGN, was $27 million during the third quarter. We believe we are now through most of the initial wave of early adopters, and looking ahead, we expect the nephrology opportunity to normalize into a gradual ramp. Turning to expenses, we've maintained a highly disciplined approach to cost management, prioritizing the commercialization of Cyphovry and Amphivelli, while continuing to fund the next phase of innovation for Appellus. Operating expenses were $235 million in the third quarter, down from $244 million for the same quarter last year. We continue to expect our full-year operating expenses to be in line with the OpEx levels we saw in 2024. We ended the quarter with $475 million in cash and cash equivalents. Supported by the $275 million upfront from our SOBE royalty in transaction this quarter, our strong cash position gave us the flexibility to discontinue factoring during the quarter. As a result, we now carry the incremental balance in receivables on our balance sheet rather than in cash, and we expect to realize cost savings of approximately $5 million on a go-forward annual basis. We continue to expect our cash position will be sufficient to fund the business to sustainable profitability. With that, I will now turn the call back over to Cedric. Cedric?

Thank you, Tim. We have made important progress in 2025 to date. We achieved our third approval in just four years, bringing a first-in-class C3 treatment option to people living with C3G and primary ICMPGM. many of whom had previously been living without any available options. Early feedback across the patient and nephrology communities has been enthusiastic, reflecting recognition of Empaveli's compelling efficacy profile and its value as a new treatment option. Additionally, CIFORB continues its market leadership and delivers a durable, meaningful revenue stream with opportunities for renewed growth over the long term. Combined with the cash from our SOBI deal in June, we have made steady progress on our path towards profitability. We look forward to building off the solid foundation we have laid for ourselves in the fourth quarter and into 2026. And with that, I'll turn the call over to the operator for questions and answers.

Thank you. Ladies and gentlemen, to ask the question, please press star 11 on your telephone, then wait for your name to be announced. To withdraw your question, please press star 11 again. We ask that you limit yourself to one question only. Once your question has been asked, you will then be removed from the stage. Please stand by while we compile the Q&A roster. Our first question comes from the line of John Miller with Evercore ISI. Your line is open.

Hi, guys. Thanks so much for taking my question, and congrats on all the progress and a strong CPG launch. I guess I'll ask my question about that. Do you still expect, past this first bolus of patients that you were talking about, that kidney is going to be a distributed or slow set of indications to penetrate? I think this has been your commentary and the competitor's commentary in the past. Do you expect that to continue, or is your strong penetration into these top practices indicative of the launch could be more rapid than people expect.

Thank you, John. Great to hear you, and I will hand that question over to David.

Hey, John. Thanks for the question. Appreciate it. So, first of all, we're really excited about where we are with the launch for MPVELE and C3G and primary ICMPGN. The team has done a great job, and I do suspect, you know, as we get through the end of this year that the bullets that we had talked about will be through that, and you'll see steady, consistent growth going into next year. That's our expectation.

Can we take the next question, operator?

Our next question comes from the line of Anupal Rama with JP Morgan. Your line is open.

Hey, guys. Thanks so much for taking the question. Just a quick one on syphoverein and on sampling. I think samples are on the higher end of this 10% to 15% range that we've all previously talked about. Should we expect this to now be more stabilized, or is there a chance that this continues to creep up as you expand the market? Thanks so much.

Hey, Anouk. Great hearing you. Again, I'm going to hand that over to David.

Hey, Ana Palm. Thanks for the question. So a couple things real quick. We definitely review where we are with samples in the PAP program or free goods consistently to make sure the programs are being utilized the way that we want them to be. Also, though, we are, as you know, as a company, very in tune to making sure patients have access to products. So as things continue to grow, we'll have programs available for patients.

Thank you. Our next question comes from the line of Steve Seedhouse with cancer. Your line is open.

Good morning. Thanks for taking the questions. Just wanted to ask a few specifics on C3G. So first, can you break out just of the 150-odd patients, how many are C3G, how many are ICMPGN, pre- versus post-transplant, adult versus adolescent? And then also, do you know if anyone has switched from Febhalta to Empivelli And do you have a sense of your market share in C3G, just how many patients are on Fadhalto versus Zantabella? Thank you.

Thank you, Steve. Great questions. This is David. So you're right. We have 152 start forms. Roughly 50 of those came through our EAP program. Consistently to label, we've seen start forms come through across the broad label, which is positive, and for both indications. And we are seeing Fab-Alta switches as a result of the information we've gotten from physicians as a result of our efficacy, in some cases some tolerability, and the ability for them to dose twice weekly with Empaveli versus twice daily with the competitive product.

Thank you. Please stand by for our next question. Our next question comes from the line of Yigal. with the city group. Your line is open. Check to see if you're on mute, you guys.

Sorry about that. Hi, can you hear me? Yeah, so this is also, thanks for taking the question. This is also a specific question on the launch. I think, David, you mentioned that 50 of the patients are in the process of converting to commercial drug. These are the ones rolling over from the clinical trials. It's just not clear. Are those actually on drug at this point? Are they still in process? And then the incremental other 102, could you just comment on, you know, what fraction of those have started Mpivelli and approximately how long they've been on the drug since the end of July? Thank you.

You bet. Thank you for the question. So you're correct. There's roughly 50 patients on EAP. Our goal is to make sure all of them make it to commercial product by the end of the year. And of the rest that have come in for new start forms, we are still working through the process with many of them. Remember, it takes four to six weeks for those patients to typically get from start to finish and get product. And that process is also being worked up as we move through the end of the year.

Okay. Thank you.

Thank you. Our next question comes from the line of Salveen Richter with Goldman Sachs. Your line is open.

Hi, good morning. Thanks for taking our question. This is Elizabeth on for Salveen. Just one from us on that four to six week time frame from start to finish of getting product of Empaveli to treatment. When do you think we could start to see kind of an acceleration there? And what do you think that could normalize as? Thank you.

Yeah, thank you very much, Elizabeth. So a couple things to keep in mind. That's typical for most, you know, rare disease launches, in particular where you have a REMS and vaccinations and a start form that has to go in from a physician. The other thing that we're continuing to work through is the policies that are being written at the payer, which also takes some work early on in the process to make sure that that transition from four to six weeks comes down to less than that period. So we're working through that now, and we'll have details as we move forward.

Thank you. Our next question comes from the line of Akash Tawiri with Jefferies. Your line is open.

Hi, this is Kathy on for Akash. So, SOFRI REV stayed flat at $1.61 million quarter-by-quarter and injection growth was 4%. So, one, do you see this as a floor for SISO before other components like long-term efficacy data or PSF come into play? And then two, one, can we assume a return to growth for syphobry, or do you think it stays at this level given you're not assuming patient funding gets resolved near term?

Hi. Thank you, Kathy. So this is Tim. So from a growth perspective, this quarter we feel very good about the underlying demand growth of 4%. As we mentioned in the prepared remarks, the bulk of those That increase in demand came from free goods. So that was a headwind that we've been experiencing for the last three quarters or so, and the headwind has amounted to approximately $40 million over the course of the last three quarters. Now, over the long term, beyond these short-term dynamics, as Cedric and Caroline mentioned in their prepared remarks, we have a lot of compelling opportunities to reinvigorate CyphoVis growth. Those include the pre-filled syringe, among others, and we'll get, you know, more visibility to you on those, you know, at the beginning of the year.

Thank you. Our next question comes from the line of Colleen Cussey with Bayer. Your line is open.

Great. Good morning. Congrats on the progress, and thanks for taking our questions. You spoke to some learnings of prescribers' habits. and C3G and ICMPGN at this early stage of launch. Can you elaborate on that a little bit and what the implications are for the launch? Thank you.

Yeah, this is David. Thank you. And I'll hand it over to Caroline, too, if you have any comments on the medical side. I can tell you that we've been very pleased with the fact that we have a very open label. And we've seen patients come through that are aligned to all of the indications for both indications and the label, which is very positive. What we're learning now is making sure that we get through the process and education with the top 20 accounts, and also make sure that we are continuing to canvas and have the conversations with all of the accounts beyond that. So it's a new indication and a new product for folks, and they're learning how to adjust to it, but we're excited about the launch so far.

And what we've been hearing from physicians is that they are excited about our data, the robustness of it, reduction in proteinuria and our 52-week results will be presented at the American Society of Nephrology amongst other abstracts that we have highlighting the reductions in proteinuria.

Maybe one last thing here from me. This is Cedric. It's been really gratifying to see how well we kind of we're prepared and understand the landscape. We're very happy with the demographics that we have calculated, the ramp forecast we've created. So, you know, it's gratifying to see the results from clinical trials translate in the real world the way it does.

Thank you. Our next question comes from the line of Ellen Hortz with TD Cohen. Your line is open.

Hi, guys. I'm on peripheral this morning. Congrats on the quarter. Just one question from us. On syphovir, has there been any progress with the Good Days Copay Assistance Charity? Is there any visibility on when and if it can be funded to assist GA patients? Thanks.

Hi. Thank you for the question. This is Tim. So there's been some progress in the sense that we understand that the The largest of these groups is open for existing patients, but unfortunately not for new patients, and you can check that on the website. But as far as we know and as far as our guidance that we gave in terms of this quarter, we don't expect anything to change with respect to the patient assistance organizations.

Thank you. Our next question comes from the line of Jade Momin with CIFL. Your line is open.

Hi, this is for Annabelle. Two questions. The first one is for CDGIC-BGN. For that one-third shared market with Tabhalta, how do you expect prescribers, how do you expect that market to vibrate? What type of patients with our physicians starting Tabhalta in and what type of patients would be preferred for Empaveli.

Yeah, thank you for that question. This is Cedric. So I think that, look, the efficacy profile that was established in the VALIANT trial across all of the patient populations that we have tested and that we've spoken about, that is really what stands out there. So this is something that we believe is going to be really important in a segment of physicians that cares deeply about differentiated efficacy. So yeah, I think we have, with the broad label that we have, we have an opportunity to really kind of go through segment by segment. We've talked before about the fact that post-transplant patients are a particularly interesting group for obvious reasons. Most transplanted patients will relapse Now, it takes a little bit of time to get on protocols, et cetera, but that's a very exciting group of patients that we're looking forward to being able to help. And then, of course, patients that are advanced, at risk of going into end-stage renal disease, and then the fact that we have pediatrics in our label as well and be able to offer something to patients 12 years to 18 years is very attractive to the nephrology community as well.

Thank you. And about one more on Fipro briefly. It's been on the market for a couple of years now. And if you go by the patterns and what A and B, we might start to see patients drop off at this stage. What are you seeing as far as persistence on treatment?

Compliance. Oh, thank you for the question. Well, with our every other month dosing, which is very in line with anti-VEG treatments, we're hearing from our physicians that patients are being compliant with treatment. And there will be some long-term data coming out from our open label extension next year.

Great. Thank you, guys.

Thank you. Our next question comes from the line of Latchin Hanbury Brown with Wim Blair. Your line is open.

Hey, guys. Thanks for the question. I noticed the new patient share ticked down a few points this quarter. I was wondering if there's any underlying dynamic that changed in the quarter that drove that, or is that just sort of noise fluctuating a few percentage points, and it's kind of reached a point of stability here?

Yeah, great. Thanks for the question. This is David. So first of all, we're very confident in where we are competitively. And just a reminder, we're 52% on MBRXs, and over 60% we continue to hold MBRXs. and have held for TRXs. You know, you're exactly right. What sometimes you'll see is a fluctuation in NBRXs up or down, but we're confident in the consistent numbers that we've seen in reporting today.

Thank you. Our next question comes from the line of Derek Archela with Wells Fargo. Your line is open.

Hey, good morning, and thanks for taking the questions. Maybe just two from us. First on Cyphery, I guess, how do you think about pre-filled syringe? The checks that we've done on that, you know, it seems like docs would be pretty enthusiastic. So, you know, when could that be made available? And how do you think that, you know, changes the growth trajectory? Is it more, you know, shifting share or expanding the market? And then I didn't know if, you know, I joined late. So just in terms of empathy, you know, start forms, any comments on trends post the quarter?

Thanks. Hi, Derek. Great hearing you. Thank you so much. Yeah, the pre-filled syringe is something that is really important in the context of the retina physicians. It improves the flow in their practices, makes it easier to handle the workload. We have been working on a pre-filled syringe. That pre-filled syringe is currently being tested in the clinic. We're not guiding on timelines to when it will actually be available for competitive reasons, but the quality of the syringe that we have has met the high expectations that we've had and super excited about going to market with that. I think it's also worth mentioning here that within kind of the type of physicians that treat patients with geographic atrophy, there are a lot of physicians that occasionally use Cyphovry, not on a regular basis. Those are physicians that I suspect are going to be excited about kind of moving towards a more routine involvement of GA patients into their practices. But even for those physicians that have not yet embraced Cyphovir as a treatment for their patients, we know that many of them are waiting for the pre-filled syringe to start treating this terrible disease. I don't know, Caroline, if you want to add something.

Well, as a retina physician, I will say that it really increases convenience, consistency, and safety to have a pre-filled syringe. And the requirements are very high for quality, and I'm really, really pleased with where we're headed with this. There was another part to the question.

So Derek, just the last part of that question, thank you again. So from a launch perspective, obviously we feel great. Beyond the guidance that we gave in terms of the start forms for the prepared remarks, I don't think we're not guiding any further than that, but we're happy to look forward to giving you an update at the year-end call.

Thank you. Our next question comes from the line of Byron Amin with Piper Sandler. Your line is open.

Yeah, hi, guys. Thanks for taking my questions. You know, this morning, Estella just revised ISRV sales guidance downward by $200 million. And so they're clearly seeing headwinds in GA market growth. Given that data point and, you know, your low-to-mid single injection growth that you project, do you feel it's due to undertreatment? And what shifts that dynamic with retina physicians?

Yeah, I mean, so I'll start. So I'll just confirm what you're saying, which is that we do see – a significant headwind for these patients who are trying to get treated and want to get treated but can't afford it. So it's had a huge impact on the market in general. And at least our discussions with retinal specialists suggest that many of them are not treating GA patients or not even having the conversation they should be having with GA patients because this has created a logistical as well as a financial headwind. I hope that answers your question.

I think what can shift the dynamics with physicians also are multiple things that we're working on at Appalachia. We're the science company. We have robust data. We're working on educating physicians using artificial intelligence, which they can also use for patients. We're working on a pre-filled syringe, and we have multiple new things coming forward to impact physicians and patients.

Great. Thank you.

Thank you. Our next question comes from the line of Judah Frommer with Morgan Stanley. Your line is open.

Yeah. Hi, guys. Thanks for taking the questions. Maybe just a couple follow-ups. I guess on patient start forums for C3G and ICMPGN, can you comment on just how they came in versus internal expectations? Sounds like they came in reasonably well. And then on just the sampling for SIFO-VRI. Any commentary you can make on how much of that is self-driven versus competitive dynamics on sampling? Thank you.

Yeah, thank you so much. For the expectations with C3G and ICMP-Gen, as I outlined earlier, this is very much in line with what we had expected. We have high expectations. We also feel very good about the demographics that we have established. That number of 5,000, we believe, robust conservative estimates for the number of patients that are out there and could be helped with our product. Then your question on safe phobia, I'm sorry, but you were breaking up.

I can answer it. It's on the samples in the free goods. So your question was, is there a competitive dynamic? I don't think that's necessarily the case. What we do know is if someone's reaching for a free good, that's true demand. It's a patient that wants to be treated. It's a physician that wants to treat the patient. And we have those programs in place and monitor them regularly to make sure that they're, you know, within the guidelines that we want to have followed, but they're accessible because patients that want to go on treatment, we believe, should be able to do that.

Thanks. Thank you. Our next question comes from the line of Ryan Deschner with Raymond James. Your line is open. It's open. Thank you.

Thank you very much. Can you remind us when the actual date Empaveli was first made available to patients for the C3G ICMPGN launch? And then also, do you have an update on the rough timeline for a top-line readout from the Phase 2 study for syphobry and APL3007? Thanks.

This is David. I'll answer the first part of the question. We launched the product in the week of July 28th, and I'll hand the other portion of the question over on

Yeah, so thank you for that question. So the trial is enrolling. We're very excited about this trial. As a reminder, with 3007, what we do is combine CyFovri with a subcutaneous injection that is an siRNA product, which brings down the systemic levels of C3 by approximately 90%, and the objective there is to go from every two months to every three months dosing and to then obviously, of course, see an outsized effect on the efficacy side. We're not guiding in terms of when that study will be completed. It's currently enrolling and has a one-year endpoint readout. Thank you.

Thank you. Our next question comes from the line of Douglas Taw with HC Wainwright. Your line is open.

Hi, good morning. Thanks for taking the questions. Tim, I think it was you that sort of mentioned that, you know, sort of there's an issue with some practices, you know, sort of just having with the lack of, you know, co-pay support, sort of a backlog or sort of operational challenges with practices if, you know, because they're not able to easily put patients on treatment. Is that in terms of just the headache within the practice in terms of, you know, just the time it takes to sort of adjudicate benefits and follow that patient, or is it just this sort of patient having an unrealistic expectation of starting treatment and then having themselves sort of put off and sort of having to deal with the frustration on that side?

Yeah, it's really a very complicated situation for the physicians as well as for the patients, right? You know, kind of figuring out who can afford co-pay, who cannot. I mean, there's a lot that goes into it. There's a lot of chair time that is lost by the physician in that process. And as Tim outlined earlier, what we've seen this year is, of course, you know, kind of a lot of slowdown that was driven by these dynamics, not just on the GA side, also on the wet AMD side. where a lot of practices have temporarily paused, even bringing on new patients to avoid having those discussions. So these are all things that are headwinds that we'll have to find a new place of settlement, but we are working hard on it. We can help practices with availability and access, of course, but the foundation is something that we're separated from, of course.

I'll also add that it particularly affects GA patients because there is a generic alternative in the wet AMD space. There is no generic alternative in the GA space.

And if I can, on the kidney launch, I'm just curious. I know, you know, obviously something that you sort of, people have been wondering about in terms of the identification of patients with C3G and ICMPMG, since it does require a biopsy. Have you seen evidence that now there are is an available treatment like Empivelli or such an efficacious treatment that clinicians are biopsying more regularly or more aggressively than they were in the past? Thank you.

Well, that typically happens when there's a new treatment available for something when there was no previous treatment. that there are patients that come out of the woodwork, and clinicians are also more motivated to make the diagnosis so they can more effectively treat this disease, which does ultimately end in end-stage renal failure. Thank you.

Thank you. Our next question comes from the line of Greg Sinonovich with Mizuho. Your line is open.

Hey, good morning. Thank you for taking my question and congrats on the progress. Just wanted to go back to Empaveli. I might have missed it before, but any way you can provide a sense of the breakout in terms of the revenue and what came from P&H and what came from the new rare kidney indications and how the 152 and new patient start forms, how that might have contributed to whatever contribution there was to Empevelli revenue from the new rare kidney indications. Thanks.

Hey, Greg. Thank you for the question. This is Tim. Yeah, so you can look at our PNH revenue for the last few quarters. Last quarter, we reported, I think, $20.3 million in Empevelli revenue. And that market has been relatively static. So I think You know, from the perspective of revenue, you can maybe back out a little bit there and, you know, look at the fact that we probably are also putting a little bit into inventory at the distributor. So, you know, on a combined basis, we don't break out that in terms of revenue, and we don't plan to break that out because it is hard for us to do that. And then from, you know, can you repeat the second part of the question? I apologize.

Yeah, just, you know, if we do, and thanks for that clarity on maybe assuming, you know, $20 million-ish or so from P&H and then maybe some inventory bill, but whatever the balance is for Empaveli revenue in the quarter from the new rare kidney indications, just trying to get a sense of if you did provide us with 152 in terms of the patient start forms, how much of that is kind of translating into that that balance of revenue specifically in rare kidney and just trying to get a sense of what fourth quarter might look like, understanding that you're not providing, you know, sales guidance per se.

Yeah, we're not providing sales guidance. We did give you some guidance on sort of an expectation around start forms for the year end, which was 225. So, you know, look, I think the way to think about this probably is, you know, looking at the, you know, the time to getting on drug from start form to getting on drug is approximately four to six weeks. And I would just work backwards from that. Okay.

Thanks so much.

Thank you, Greg.

Thank you. Our next question comes from the line of Lisa Walter with RBC. Your line is open.

Oh, great. Thanks so much for taking our questions and congrats on the kidney launch. I was just wondering if you could provide us any color on the pivotal trial design for FSGS and DGF. Thanks so much.

Thank you so much. So these trials have just started. We're not providing details beyond what's available on clinicaltrials.gov, but we're really excited about the opportunity that we have in FSGS and DGF. FSGS, as a reminder, affects about 13,000 patients in the U.S., similar in terms of severity to the patient and the patient's kidney to what we see with T3G and ICMPGN. And we're looking forward to hopefully having a treatment available for these patients. With delayed graft function, we are looking into a three-month treatment with Empaveli to protect these kidneys that typically come from deceased donors. of which there are 21,000 per year, and about probably 30% of those patients will suffer from that so-called delayed graft function, which is an increase in creatinine in the week post-transplant.

Thank you.

Thank you.

Ladies and gentlemen, we have time for our one last question, and that will come from the line of It's a follow-up question from the line of YeGale Notramovitz with Citigroup. The line is open.

Oh, thank you. Thank you. Just one quick follow-up, please, on the pre-filled syringe. Cedric or Tim or David, I'm just wondering, is that going to be offered also as samples, or will it only be restricted to just commercial drug for the pre-filled syringe?

Thanks. This is David. So we will launch with commercial product, and then over time we'll have samples available as we get into the launch.

Okay. Thank you.

Thank you. I would like to turn the call back over to Cedric for closing remarks.

Thank you so much, and thank you, everybody, for your thoughtful questions. This concludes the APELIS third quarter earnings call, and I hope you all have a wonderful rest of the day.

Ladies and gentlemen that concludes today's conference. Thank you for your participation. You may now disconnect.