Good morning, ladies and gentlemen. Thank you for standing by, and welcome to the Appellus Pharmaceuticals' fourth quarter and full year 2025 earnings conference call. Please be advised that today's call is being recorded. I will now turn the call over to Eva Stronowski, Head of Investor Relations. Please, go ahead.

Good morning, and thank you for joining us to discuss Appellus' fourth quarter and full year 2025 financial results. With me on the call are Co-Founder and Chief Executive Officer, Dr. Cedric Francois, Executive Vice President of Commercial, David Atchison, Chief Medical Officer, Dr. Caroline Bommel, 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 Now, I'll turn the call over to Patrick.

Thank you, Eva, and thank you all for joining us this morning. Before turning to our fourth quarter results, I'd like to briefly reflect on the progress Apedis made over the course of 2025. It was a year of disciplined execution and foundation building for our company. We strengthened our commercial franchises, advanced key programs across our pipeline, and continued to demonstrate the value of our differentiated T3 approach, all while maintaining a strong balance sheet and a clear focus on long-term value creation. These foundations position us well as we move ahead, with clear priorities centered on execution, growth and unlocking the next set of value-creating inflection points for Aperis. At our core, Aperis is a company focused on complement biology, specifically targeting C3, the central hub of the complement cascade. By intervening at this central point where all complement pathways converge, we take a fundamentally different approach that enables comprehensive disease control at the root cause while preserving essential immune function. This strategy continues to differentiate us scientifically and commercially and positions us to address a broad range of serious, complement-driven diseases. Our 2026 focus remains anchored in our three strategic pillars. First, strengthening Saifovri's leadership in geographic atrophy. Second, driving growth with Mpavelli across rare kidney diseases And third, advancing an innovative pipeline that underpins our next wave of growth Starting with Cyphobri Cyphobri continues to be a resilient and durable business In 2025, we delivered steady growth in total injections and we expect SIFOBIT to remain a stable and meaningful revenue stream through 2026. Last month, co-pay assistance programs at third-party organizations began reopening to new patients. While we do not have visibility into how activity may ramp over time, we are encouraged that patients may be able to gain access to treatment. Looking ahead, we are advancing key initiatives to lay the foundation for accelerated growth in 2027, including a best-in-class pre-filled syringe and OCTF, our AI-enabled approach to visualize the functional benefits Sifovir can provide for patients. Together, these initiatives are designed to make treatment more tangible, improve workflow, and support broader adoption over time. Turning now to our second pillar, Empavelli. Empavelli is our near-term growth engine, and its launch trajectory reinforces our confidence in its long-term value. Following FDA approval in July for patients with C3G and primary ICMPGN, the launch has progressed fully in line with our internal expectations, reflecting strong execution and early market receptivity. After its first full quarter on the market, Empavelli achieved more than 5% market penetration, significantly outpacing other rare nephrology launches. We continue to receive outstanding feedback from the community, with growing appreciation of Empavelli's value proposition following the publication of our data in the New England Journal of Medicine. We believe Empaveri's strong efficacy and safety profile will continue to drive adoption and that over time it has the potential to be used by up to 50% of the estimated 5,000 US patient population. Lastly, our third pillar, which is our innovative pipeline. In nephrology, we are building on the momentum of Empaveri and expanding the franchise into new indications, with pivotal trials now underway in focal segmental glomerulosclerosis and delayed graft function. In geographic atrophy, we are further bolstering SIFOVRI's leadership through our next generation strategy, combining SIFOVRI with APL3007, designed to enhance efficacy, patient experience and further differentiate our offerings. We are also excited to advance APL 9099, our category-defining SCRM program. This first-in-class base-editing approach has the potential to disrupt a multi-billion-dollar market and enable a one-and-done treatment paradigm across multiple indications. These programs reflect the breadth, strategic depth, and long-term ambition of our pipeline. With a strong balance sheet and a growing commercial revenue base, we are well positioned to self-fund our pipeline and drive long-term value through discipline's financial execution. And with that, I will now turn the call over to David for an update on our commercial performance.

Thank you, Cedric, and good morning, everyone. I'll begin with SIFOVRI. As Cedric highlighted, 2025 reinforced that SIFOVRI is a resilient and durable business. While full-year revenue was modestly down compared to 2024, largely due to elevated use of free goods, the underlying demand remained strong with total injections growing approximately 17% year-over-year. Sifovir continues to lead the GA market. Physicians and patients value its differentiated profile, including robust efficacy and the flexibility of dosing as few as six times per year. Payer coverage remains strong with preferred status across a broad range of plans. As the GA market continues to evolve, we see meaningful opportunity for SIFOBRI and are focused on three priorities to support continued expansion and long-term growth. First, sharpening our field engagement through physician segmentation, refined messaging, and a greater emphasis on early career retina specialists. Second, reinforcing our data leadership in GA. Sifovary is supported by the most extensive clinical and real-world evidence base in the category, anchored by five-year Gale data. And third, advancing innovation with a best-in-class pre-filled syringe and OCTF. Together, these initiatives are foundational to supporting broader growth in 2027 and beyond. Turning to Impavelli, we are very pleased with the progress in C3G and primary ICM-DGN launch, with early uptake fully consistent with our expectations. Following its first full quarter post-launch, Impavelli achieved more than 5% market penetration. This level of early adoption is particularly notable in nephrology, a specialty known for conservative prescribing behavior and high evidentiary thresholds. As of year-end 2025, we received 267 cumulative patient start forms, reflecting strong early demand and a growing patient pipeline. Demand is being driven by broad engagement across the nephrology community and supported by favorable payer access, with 95% of published policies reimbursing to label or with minimal restrictions. Physicians consistently highlight Ampoveli's compelling efficacy profile, along with the convenience and ease of use of its on-body auto-injector and twice-weekly dosing. With its broad label, Ampoveli is the only approved therapy for approximately two-thirds of patients with C3G and primary ICMPGN in the U.S. As the launch has progressed, we have expanded meaningfully across the prescriber community, increasing both the breadth and depth of engagement. Over time, physicians are gaining experience in treating additional patients, reflecting growing confidence as the launch matures. Importantly, this execution has translated into strong patient pipelines. Early identification and engagement efforts over the first six months have positioned us well for continued growth, and we remain focused on broadening and deepening that pipeline as the market develops. As we look ahead, our 2026 launch priorities are focused on three clear areas. First, strengthening the patient identification through targeted medical education to both improve diagnosis and drive urgency around earlier treatment. Second, expanding engagement with prescribing physicians. We began the launch with a disciplined focus on our top 20 accounts, which represent more than 30% of the overall market and have accounted for approximately one-third of patient start forms. We are now systematically broadening engagement across additional tiers through targeted field activity and peer-to-peer education. And third, deepening adoption across patient segments. We continue to see strong interest from pediatric and post-transplant patients with growing opportunity in the adult population as the treatment paradigm shifts and clinical practice continues to evolve. Overall, the launch is progressing very well. we enter 2026 with strong momentum, and we believe that strength will continue through the year with some quarter-to-quarter variability. We believe Ampoveli is on a clear trajectory to blockbuster status, and that it could ultimately be used by up to half of U.S. C3G and primary ICN-BGN patient population.

With that, I'll turn the call over to Caroline. it thanks David I'll begin with syphovry as the only approved therapy that targets c3 syphovry addresses the central biology driving geographic atrophy which continues to differentiate its clinical profile in the fourth quarter we announced new five-year data from a post hoc analysis of the gale extension study which showed that syphovry delayed progression of geographic atrophy by approximately 1.5 years in patients with non-suprovial ga when compared to sham or projected sham we look forward to presenting the full five-year data set at the MACF Society later this week as one of our eight oral presentations at the conference looking ahead we are advancing two initiatives designed to support clinical decision-making and real-world use. First, our pre-filled syringe, intended to improve efficiency in retina practices. The clinical study is complete, and we are working toward a regulatory submission in the first half of this year. Second, we continue to make important progress with functional OCT, our AI-enabled approach to visualizing functional benefit in GA. We recently shared data at the angiogenesis meeting earlier this month and plan to make the tool available for research use in retina practices in the second half of this year. In parallel, we continue to advance the Phase II study of syphovry in combination with APL-3007 as a next-generation approach designed to more comprehensively block complement activity in the retina and choroid. We expect to share top-line data in 2027. Now turning to Ampavelli in C3G and primary ICMP-DN. Physician feedback and the recent New England Journal of Medicine publication continue to reinforce Ampavelli's differentiated profile. As the only C3 targeting therapy, Amphivelli has demonstrated the trifecta of efficacy outcomes with direct clearance of C3 deposits translating into reduced proteinuria and stabilization of kidney function. These data reinforce our confidence in Amphivelli's mechanism and its potential to redefine treatments in complement mediated kidney disease. We also recently initiated pivotal trials with enfivelli in FSGS and DGF, two additional high unmet knee kidney indications. Both conditions are strongly linked to complement activation and currently have no FDA-approved therapies. Finally, I'll briefly touch on APL 9099, our FCRN program. This first-in-class face editing approach is designed to reduce IgG levels while preserving albumin which we believe addresses important limitations of existing FCRN therapies we expect to submit an IND in the second half of this year and look forward to sharing more details as the program progresses with that I'll now turn the call over to Tim thank you Caroline I'll now walk through our financial results.

Additional details are included in this morning's press release. Total revenue for the fourth quarter and full year 2025 was $200 million and $1 billion, respectively. As a reminder, full year 2025 revenue includes the one-time $275 million upfront payment from the SOBI royalty repurchase agreement. We reported SIFOVRI net product revenue of $155 million for the fourth quarter and $587 million for the full year 2025. During the fourth quarter, we delivered approximately 102,000 SIFOVRI doses to physician offices, including approximately 89,000 commercial doses and 13,000 free goods doses. As previously discussed, reported revenue was meaningfully impacted due to elevated free goods utilization through 2025. Looking ahead, we remain committed to supporting patient access while recognizing the free goods utilization may evolve over time as third-party programs resume activity. Turning to gross-to-net, SIFOVRI adjustments in the fourth quarter trended just above the mid-20% range. In 2026, we expect gross-to-net to be in the high 20% range, reflecting the normal stepwise evolution of the buy-and-bill market. importantly based on our current pricing strategy we expect net price to remain relatively stable through 2026 and we remain confident in our access position as we exited 2025 we took a disciplined approach to inventory management we are comfortable with the current channel levels we therefore expect a modest inventory reduction in the first quarter alongside typical seasonal dynamics including Medicare re-verifications. Overall, SIFOVRI remains a meaningful and durable foundation for appellers. In 2026, we are focused on disciplined execution while advancing initiatives that position the business for renewed growth in 2027 and beyond. Moving to Empervelli, we report a U.S. net product revenue of $35 million for the fourth quarter and $102 million for the full year 2025. As David noted earlier, the launch continues to progress very well, and based on current trends, we believe Ampoveli is on a clear path to blockbuster status. For operating expenses, we continue to maintain a highly disciplined approach to cost management. Operating expenses were $251 million in the fourth quarter, compared with $239 million in the same period last year. For the full year 2025, operating expenses were in line with our expectations and consistent with 2024 levels. In 2026, we expect operating expenses to be modestly higher with incremental investment in the newly initiated pivotal trials for FSGS and DGF, as well as certain milestone payments, largely offset by a decrease in SGMA reflecting ongoing operating efficiency and resource optimization. We ended the year with $466 million in cash and cash equivalents, which we believe provides us with substantial flexibility and the resources to fund the business to profitability. As a reminder, SOBE recently received European Commission approval for Aspovelli in C3G and primary ICM PGN, which triggered a $25 million milestone payment to Appellus during the first quarter of this year. We also remain focused on prudent capital structure management. We have approximately $94 million of convertible debt outstanding, which matures in September of this year, and we are actively evaluating a range of alternatives to address this obligation in a thoughtful and disciplined way. And with that, I will now turn the call back over to Cedric.

Thank you, Tim. As we move through 2026, our priorities are clear. We are focused on disciplined execution across our commercial portfolio, advancing initiatives that support long-term growth, and continuing to deliver meaningful impact for patients. EmpraBeddy is gaining traction in C3G and primary ICMPGN, while SIFO we provide a durable foundation as we position the franchise for its next phase of growth. Supported by a strong balance sheet and financial rigor, we are operating from a position of strength and remain confident in our ability to create durable value for patients and shareholders. And with that, I will now turn the call over to the operator for Q&A.

As a reminder, to ask a question, you will need to press star 11 on your telephone. To remove yourself from the queue, you may press star 11 again. We ask that you please limit yourself to one question and one follow-up to allow everyone the opportunity to participate. Please stand by while we compile the Q&A roster. Our first question comes from the line of John Miller of Evercore ISI. Please go ahead, John.

Hi, guys. Thanks so much for taking my question, and congrats on the progress throughout 25. I'd like to use my one question to ask about MPaVeli launch as we get into 26. You mentioned opening to broaden the accounts there and improve patient identification diagnosis and all of that, but I noticed that one of the things that you didn't mention when you were listing the indications where there was strong growth potential was ICMPGN, where obviously you have a differentiated label, but historically it's been a little bit more challenging to find those patients. Can you talk a little bit about, you know, the breakdown of different indications throughout 2026, where you think the low-hanging fruit is, where we can see real growth in the near term, and what it will take to break open some of those indication subsets that are a little bit tougher to diagnose and get on treatment?

Thank you so much, John, and great hearing you, and thank you, everyone, for joining. So, Empyavedi is on a clear path to blockbuster status, and as you correctly outlined, John, There's not just ICMPGN, there's also the fact that in the Valiant study, we studied MPA-Vedi in the pediatric population, as well as in a post-transplant setting as well. Now, specifically as it relates to ICMPGN, we believe that the epidemiology in total between the two indications is approximately 5,000 patients in the U.S., split more or less 50-50 between those two indications. While we're not providing exact breakdowns as to where in the population things sit at the moment, it is worth noting that in the pediatric population, ICMPGN in the post-transplant segment, we see important pick-up and differentiation, and that of course contributed to achieving more than 5% penetration after the first full quarter in Q4, and contributes to our confidence of reaching up to 50% of those 5,000 patients at peak.

Thanks, Hendrick, but I guess if you're going to see 50% penetration at peak and ICMPGN is 50% of the U.S. population, I guess I'm asking, are you going to see equivalent penetration across those different subpopulations, those different subindications, you know, by the end of the day, or are there places that are going to remain more difficult to penetrate?

It's a little early to say that exactly, I think, at this moment in time. You know, it's also important to note that there's quite a bit of overlap between these two indications. There's not kind of a hard separation between them in the sense that you can have a patient with a biopsy one day that, you know, is more leaning towards C3G and on another biopsy can lean more towards ICMPGN, which is why it is so important to have covered all phenotypes of these diseases in the clinical trials that we ran. It's a little bit too early to provide more specifics on that.

Thank you.

Our next question comes from the line of Anupam Rama of J.P. Morgan. Your line is open, Anupam.

Hey, guys.

Thanks so much for taking the question.

For Cyphovry, you've got the five-year GAIL data this Friday that you guys highlighted. What would you have us focus in on within these data? Thanks so much.

Thank you so much, Anupa. Well, the important benefits and the continued safety profile that Cyphovry provides to patients with geographic atrophy, right? So it is by far the largest data set ever generated in geographic atrophy. And, you know, what we found through the course of following these patients for a full five-year period is that patients who are on treatment for five years can save as much as one and a half year of tissue. So, as I think you can appreciate, that's an enormous benefit to a 70- or 75-year-old individual who obviously, you know, in the twilights of their lives depend so much on their vision. So we're incredibly proud and incredibly happy with the data that we have generated and look forward to presenting it on Friday. I don't know, Caroline, if she would like to add something.

Oh, thank you, Cedric. I think what will be meaningful for a retina physician is that we have this extended trial with five years of data that we continue to show increasing effects over time and that retina tissue can be meaningfully saved. And these findings might lead to earlier treatment for patients with geographic atrophy. So we really look forward to presenting this data.

Thank you.

Thanks so much. Thank you. Our next question comes from the line of Tazeen Ahmad of Bank of America. Your line is open, Tazeen.

Okay, great. Kate, thanks for taking my questions, and good morning. I maybe wanted to follow up on that 50% penetration for MFAVELI. How long do you think it's going to take to reach that? I know that a big point of discussion among investors is like the ramp of your launch. Is it going to be more steady, or could it accelerate and become more steep? So, any thoughts you can provide on patient-binding efforts and what you think, realistically, the time to onboard patients will take, that would be helpful. And then, can you just talk about what the competitive dynamics are so far relative to how a doctor is reviewing Emphivelli versus TAPHOLTA? What are the types of patients that they might still be waiting to see if Emphivelli might be better than relative to TAPHOLTA? Thank you.

Thank you so much, Stazine. Well, as it relates to the ramp, you know, I think you correctly outlined that we should expect steady ramp and steady growth as is quite typical in rare diseases. And again, I think, you know, we have seen that happen in the past couple of months and expect that to continue to be the case. Competitively, as already outlined when John asked the question, there is kind of the clear differentiation that we have in kind of unique positioning without competition right now in the pediatric segments as well as an ICM-PGM is of course a huge advantage also in the pediatric population you know I think the disease tends to progress more quickly and what you see in the fields based on what we have seen since the launch is that the appreciation for the efficacy and safety profile of the drug really stands out also the post transcend segments of course that is a very important place most majority of patients with these diseases will have a relapse because this is a genetic condition at the end of the day thank you our next question comes from the line of Timur of Anikov, of Cantor.

Timur, your line is open.

Hi, thank you. This is Timur on for Steve's house. For Empadeli launch, I think you mentioned the strong momentum in C3G in 2026 with quarter to quarter variability. Could you talk about some of the variability factors and do you expect to provide start forms again at some point or any other form of guidance? Thank you very much.

Thank you so much, Timur. I will hand the question over to David Atchison.

Hey, good morning. Hope you're doing well. Thank you for the question. So, on the variability, it's just ultra-rare disease. I think it's important to note that you'll see an influx of potential patients coming in on start forms that does vary, you know, week over week, month over month. So, I think it's just something that we need to pay attention to. But I feel very good about the momentum that we came into 2026 with from the launch last year on the strength of the product and the patients that we're getting on on the brand which is which is very positive um and can you repeat the second part of your question for me yeah i was just wondering about the you know the start forms or any other type of guidance for the product yeah so moving forward uh we continue to report on revenues for sure and start forms but um we're not going to give any additional guidance on start forms that we had in the third and fourth quarter.

Thank you.

Thank you. Our next question comes from the line of Ego Neshamovitz of Citigroup. Ego, your line is open.

Hi, Greg. Thank you. Can you talk a bit about the pre-filled syringe? I just want to get a sense of how much it matters for the retinodox in terms of the practice flow and efficiency. And when you say renewed growth in 2027 for syphovary, is the driver behind this statement, the launch of the PFS? And then more specifically on the practice dynamics, you know, since the space is very limited for the physicians for the fridges to store the drug, is there an advantage to the PFS in terms of practice dynamics and storing the drug with that presentation?

Thank you, Miguel. Those are excellent questions, and the PFS will make a huge difference for us. And we have, of course, our chief medical officer with us here, Carolyn, to speak a little bit more towards that.

Thank you. So, the pre-filled syringe is really a practice-enabling innovation. And this is going to offer convenience and efficiency to retina physicians. And, you know, from my experience as a clinician and also from being heavily involved in development of our pre-filled syringe, And this is going to support the ease of clinical use in patients with geographic atrophy. So we really think that this is going to be transformative for physicians and their patients. When it comes to specific about the design, I think that retina physicians put their input heavily into how we design this, including the box, the complete package, and will be very, very pleased with how it fits into the refrigerators. We also have some other things that will be helping to be transformative for SIFOVRI with renewed growth, and that's functional OCT, which was mentioned in the call.

Thank you. Thank you.

Thank you. Our next question comes from the line of Salveen Richter of Goldman Sachs. Please go ahead, Salveen.

Good morning. Thanks for taking my question. I was wondering if you could provide any further cover on the recent improvement in co-pay dynamics for SIFOVRI and how you think about the quarter-over-quarter cadence of sample use and kind of the sales trajectory as you input this into your trajectory.

Thank you so much, Selvin. Tim, can you let me know?

So, as you probably saw, Salveen, the patient assistance organization is open for reimbursement for co-pay assistance with geographic atrophy patients. This time, we don't really have any sense of what that means in terms of dynamics from a free goods perspective. As you recall, last year, we had 12% to 14% fluctuating on a quarterly basis. But really, what this represents is an important advance for the patients who have been unable to pay for their treatment in geographic atrophy.

Our next question comes from the line of Colleen Tussie of Baird. Colleen, your line is open.

Thanks for taking our questions. Congrats on all the progress. Realize for the Nephrology Phase 3 studies are just recently coming up and running now, but any color you can provide on the expectations for enrollment there. Do any of these centers have pre-existing experience with Emphivelli and just how that enrollment might pan out?

Thank you so much, Colleen, for that question. So we're very excited about these two-phase triclinical trials in FSGS and DGF, where we think the potential can make a huge difference at the Devon C3G and ICMPGN. It's still a bit early to give projections on what the enrollment will look like, but the excitement around kind of continuing the trajectory in the kidney is very strong. What really stood out from the Valium study is the exquisite target engagement and the control of the complement pathways that we see in the glomerulus, which we believe will translate in a- Great, thank you.

Thank you. Thank you. Our next question comes from the line of Phil Nadeau. T.D. Cohen, your line is open, Phil.

Good morning, thanks for taking our question. We wanted to focus on SIFOVRI revenue trends for Q1 in 2026. Tim, putting your comments together, it sounds like you expect typical seasonal factors for Q1. Last year, sales were down 37 million quarter-over-quarter in Q1, 25, versus Q4, 24, although there was a big impact of free product in that downtick. So how will the seasonal factors in Q1 at 26 compared to Q1 at 25? And then more generally for 2026, it sounds like you guys are suggesting relatively stable revenue for CIFO oversight. I want to make sure I understand that, that we should be modeling something full year 2026 similar to full year 2025.

So, yeah, I think the one thing to remember, there are a couple of seasonal dynamics in the first quarter, one of which we tried to manage a little bit. So, as you'll recall, last year we had a fourth quarter spike in revenue that was as a result of some inventory build across the channel. So, that included at the physician offices as well as at the distributor. We really did our best to manage that this year. So, we think there may be a bit of a modest swing in the first quarter, but much more muted than last year. We also typically have some seasonal dynamics like weather and re-verifications. in the first quarter so bearing that in mind you know you know we think you know across the year that's the main seasonal quarter for us there's a little bit at the end in the fourth quarter but as you as you rightly point out we expect sort of a modest cadence to growth over the course of the year that's helpful thank you thanks thank you our next question comes from the line of Annabelle Cimini of Stiefel.

Your line is open to Annabelle.

Hi, this is Jayad on for Annabelle. The sponsor where you visit the psychotherapy doses delivered, it was about quarter over quarter, I think you mentioned due to some seasonality, but there was an improved split favoring commercial doses, agnostic of the pay, the co-pay assistance funds coming back, do you expect that split to be more favorable for commercial doses going forward in 2026?

Sure. So thanks for the question. So what we really felt happened in the fourth quarter was a touch of seasonality. You know, when you look at the amount of doses we had, it was 89,000 and sort of their roughly 90 days in a quarter. We had a couple of, you know, a longer holiday stretch that may have impacted things. So it was really, you know, not a significant change from a commercial doses perspective, you know, in the context of that seasonality in our view. But from the free goods perspective, we saw a range of 12 to 14 percent over the course of 2025 that bounced around. And so this was, I think, pretty much in line with what we expected in the fourth quarter. As you may recall, sometime in the third quarter, the patient-tool-tay assistance organization was open for existing patients, and that may have led to a small downtick in the total free goods in the fourth quarter, but it's really hard to say. Thank you. Thanks.

Thank you. Our next question comes from the line of Ellie Merle of Barclays. Please go ahead, Ellie.

Hey, guys. Thanks so much for taking the question. Two for me is, what are you looking to see in the Phase 2 data by SilverA in combo with APL 307 next year, and how are you thinking about what would be meaningful there? And then just a clarification on the C3G ICM-PTN comments. The 50% penetration that you mentioned, I'm sorry if I missed this, but I guess, is this the base case that you'll treat 50% or are you saying that half the population will become challenging to treat? You're trying to understand that 50% comment. Thanks for the color.

Thank you, Eli. Great hearing you. So the Gallup study is a study we're really excited about. What we do there is a subcutaneous injection with an siRNA product against C3 and that lowers the systemic levels of C3 by approximately 90%. What that does is it translates to actually a lowering of the C3 levels in the eye as well and it gives a stoichiometric advantage to Sifovary to do its job. We believe that this study, if successful, will allow us to treat every three months instead of every two months and to increase the efficacy, which is already important of course, from Sifovary to numbers well above that. What well above that means, we will define at a later time point. But I think, again, kind of really exciting study for us where I think we can, again, change the paradigm in geographic empathy as we have done before. As it relates to the C3G and HCMPGN populations, so we said we believe that up to 50% of the epidemiology would be patients that could end up being treated with Empavelli what I think is important in that context is again that we I think we're very good at having a conservative estimates of the epidemiology for C3G and ICMPGM it is noteworthy that you know our only competitor in this space as an epi that is meaningfully higher and the fact that we have more than five percent penetration in the fourth quarter which means that we had a very very strong launch among the strongest launches in rare diseases and maybe a conservative epi on our side or a combination of both so again we feel very good with where anti-veti is headed with what we did in Q4 and the trend that we continue to see as this launch progresses thank you thank you a nice Next question comes from the line of Lachlan Hanbury-Brown of William Blair.

Please go ahead, Lachlan.

There you go. Thanks for the question. I guess for Amphivelli, you previously talked about there being an initial bolus of patients and then it sort of settles down into more of a steady state, monthly or quarterly growth in new patients. I'm wondering sort of where are you at that? Are you through that bolus and into the steady state now, or are you still working through some of that initial bolus of patients that you were expecting and that you reached the steady state later this year.

Yeah, thank you, Decom. I will hand that over to David A. to answer.

Hey, good morning. Thanks for the question. So, yeah, like we talked about last year in the Q3 launch through Q4, that bolus of patients typically hits early in the launch and get on product, you know, shortly after the launch, and we saw that happen in the fourth quarter, which was great to see. Now we're at that steady state place that we talked about in the prepared remarks and what Cedric mentioned in the opening portion of some of the questions here. So, I would be confident in the continued steadiness of what we're going to see moving forward.

Great. Thank you. Our next question comes from the line of Judah Frommer of Morgan Stanley. Please go ahead, Judah.

Yeah. Thanks for taking the question. Maybe just one on the commentary around the ability to fund yourselves through the profitability. Just curious how pipeline could impact the timing and trajectory of that, specifically maybe 9099 and 3007. What are the pushes and pulls there that could move that profitability closer or further out?

Yeah, thank you, Jude. That's a great question, at least for the moment. We've incorporated all of that into our thinking when we talk about the fact that we may have, you know, a small increase in total operating expenses this year, as you'll see in 2024 and 2025. It was pretty flat overall. We may have a small increase over the course of this year, you know, with our FSGS study and our GGF study really ramping up And then some of these new programs that you mentioned, like the BEAM program coming online towards the end of the year in terms of, you know, potential larger cost structure. But ultimately, you know, we've been pretty good about managing our operating expenses, and it really comes down to, you know, to the revenue growth that will make that happen. You know, we look at the world, at least today, from, you know, from an operating expense and net revenue perspective. And if you look, you know, taking adding back stock-based compensation, we've been pretty close to an operating adjusted EBIT neutral level over the last year. And, you know, we expect that to come more into focus over the course of this year.

Thank you.

Our next question comes from the line of Douglas of H.C. Your line is open, Douglas.

Hi. Thanks for taking the question. Just on Cyphobri, David, just a couple of questions. I think last year you indicated there was sort of an initiative to help patients sort of end up on the right plan, which sort of improves their coverage of Cyphobri. I'm just curious sort of as you come into the new year if you've sort of seen meaningful progress on that, and then also I'm just curious in terms of the free goods, Are you seeing those patients sort of typically sort of get dosed with free goods and then they see that they can't get covered or can't get patient assistance and drop off? Or are you seeing sort of a persistence of it? I'm just sort of trying to understand that in terms of understanding sort of how patients are coming in and sort of identification for the market.

Thank you, Doug. David will answer the question on Cypherry, and I will – the first question, and I will then talk a little bit about the free goods.

Hey, Doug, thanks for the question. So on the re-verification piece and just kind of patients coming over on insurance plans and what we did last year, so we put a lot of effort in last year with our field reimbursement team to make sure that we can help offices get educated on which plans would be specific to patients that have a gap, right, where they couldn't get covered for a geographic atrophy treatment or specifically SIFOVRI. So we did a lot of work on that. Our appellate assist, which is our hub, has also been integral in playing a part of making sure education to both the patients and the offices during the reverification period of their insurance, which happens in the fourth quarter, coming into this year, helps them understand where they've got opportunities for treatment for benefit and payment. And all of that happened coming into this year. And I can tell you the re-verification process is winding down. It's been relatively smooth. I cannot tell you how many patients actually changed plans or moved over, but we did what we could to continue to educate so people had access to additional information. I'll hand it back over to Cedric.

Thank you, David. Well, as it relates to the free goods, I kind of want to highlight something that is really important, and that is that in 2025, we made a deep commitment as a company to support the retina practices to deal with, you know, at the end of the day, a lot of patients being in a position where they could not afford the co-pay on their products and to make sure that these patients would not go without treatment, right? So that is our medical commitment to patients, and that is what we did throughout the years last year, but we will always continue to do when it is needed. So that is really important and will continue to be important for us. I think within the context of next year as well, I think it is hard to overstate how impactful the disruption was on the workflow in the retina practices when this occurs, right? So that is something that we had to find a new place of settlement that was important. And during that period, there was inevitably kind of, I would say, a lowering of how many new patients would come on treatment with geographic atrophy because within these retina practices, that is easy to essentially punt, right? So, that dynamic is also something that you should expect to see change over time. I think what is really important and gratifying to see right now is that within the retina world, we're starting to find a new cadence and a new place of stability after what was a very difficult year for these physicians and patients.

Great. Thank you, Sajdurk. And it's great to hear about the commitment to providing drug treatments.

Thank you. Great hearing you.

Thank you. Our next question comes from the line of Derek Achila of Wells Fargo. Your question, please, Derek.

Hey, good morning, and thanks for taking the questions. You made some comments on, you know, kind of the patient pipeline for Emphivelli and C3G and ICMPG. And I guess what level of visibility do you have there?

You know, is it as granular as, you know, understanding where the patients are at certain sites you know outreach to those patients and then just a second question on you know PFS just kind of curious is it more of expand the market or is it also share games you know against the other competitor things thank you so much Derek well first of all as we list to the pipeline I think that is one of the most one of the more gratifying aspects of the launch that that we have seen first of all of course there was the epidemiology which as you all know was difficult to estimate and feeling that we really don't hit hit the bull sign in terms of estimating that and arguably conservatively estimating that then of course the very good you know one of the best rare disease launches that we are having in the kidney here with that penetration within the first full quarter but then as you mentioned also the pipeline so if you take the number of patients that we actually identified which then flow into start forms and from start forms into being on treatment that upstream pipeline today is larger than it was before the launch in spite of of course many of these patients now having transitions to start forms and being on full treatment so that tells us that again we got the epi right we continue to identify these patients and why we expect this launch to be one of steady growth and then as relates to your second question with the pre-filled syringe I think it will be a very important driver of share we have plenty of examples from the wet AMD space with anti-vegef products where it has been proven proven over and again that having a pre-filled syringe on the market makes the very important competitive advantage for a product that is one that we are working towards you You know, of course, we expect our competitor at some point to come out with a pre-filled syringe as well. But right now, we have a head start that, you know, we're very happy with and that will allow us to position ourselves well. As it relates to share, it will also make a difference. The fact that you fit better into the workflow of a retina practice makes it much easier for physicians to treat these patients. Makes it also much easier, quite frankly, for physicians to just try the products, right? I mean, it is not, instead of taking something, having to draw it from a vial through a filter needle into a syringe, et cetera, you take it out of the fridge and you try it, right? So, important differences, and I don't know, Carolyn, if you want to elaborate on that, but we're very pleased with where we are.

Yes, you know, this is a real innovation, and this will be highly meaningful to physicians to have this way to treat their patients efficiently. So I speak from my personal experience and what I've heard from colleagues that I think that this will help to expand the market for geographic atrophy.

Thank you, Caroline. And worth noting is that the pre-filterings that we have from a CMC perspective, from a quality, from – is absolutely has been spectacular for us and outpaced our own high internal expectations. So, we're really happy not just with the data which we're bringing into the market, but also with the quality of the pre-float syringe.

Great. Thanks very much.

Thank you. Our next question comes from the line of Ryan Deschner of Raymond James. Please go ahead, Ryan.

Hi. This is Anthony on for Ryan. So, we wanted to ask, can you walk us through how the specialists can potentially use OCTF and their practices, how this could increase the size of the GA market, and then if you have like an approximate timeline for when you anticipate having appreciable amounts of real-world OTCF data for analysis, and if possible, I have a follow-up.

Thank you so much, Anthony. Well, we're touching on Caroline's favorite subject here. So, for those on the call not familiar with OCTF, OCTF is functional OCT, And it is a technology that we developed in collaboration with the University of Bonn in Germany, where we used our, what is the largest data set of microperimetry data ever generated in the retina, where we used that technology to essentially take an OCT and translate an OCT image into what a real functional mapping of the retina is. In other words, what is the retinal sensitivity in a patient across the retina? And what really stands out when you analyze patients with geographic atrophy over time is the impressive loss of retinal sensitivity that these patients experience. And from a timing perspective, what you should expect to see this year, and it started at angiogenesis two weeks ago, is that we will redefine for retina specialists and for family members of patients what it means to have this disease. And why is that so important? Because right now, a lot of people believe that geographic atrophy happens on the border of a lesion. And that is not the case. It is really a penretinal neurodegenerative condition, and we can now image that. And commensurate with that, of course, we can image and quantifiably visualize what the benefit is of being on treatment with Cyphorii. In the first step this year, we will be focused on, again as I mentioned, raising the awareness around how impactful geographic atrophy is on patients, and then it becomes our mission to make this available in the retina practice so that a physician, in a one-on-one interaction with the patient can actually do that analysis assess the patient and again track what the benefit is of being on treatment with that for each of that patient Caroline is in love with this technology speaks about that every RATENAC conference and maybe want to add a couple of words physicians are really excited for this technology finally to have a way to link structure to function

This was shown at our recent presentation at angiogenesis, and I had multiple people reaching out to me after. But what I would say is that this will help with earlier diagnosis of GA. It will help physicians support the patient's journey. It will help physicians better understand this disease, and we expect it to support adoption of Cifovary, which is, you know, the currently approved agent with every other month's dosing, support their use in patients, and help keep patients on their treatment schedule, you know, with up to every other month by showing them and showing their family members how they're doing. We also hope that it helps highlight other diseases, including wet AMD and other things that we're evaluating as a research tool. Thank you.

Thank you very much. Thank you for the in-depth explanation.

Sorry. Thank you. Our next question comes from the line of Douglas McPherson of Mizzouho. Please go ahead, Douglas.

Hi there. Good morning. Thank you so much for taking my question. I'm interested in the sort of competitive dynamics of the market. Firstly, are you seeing the complement inhibitor class to 3GA, seeing that hold steady or perhaps growing modestly? And then I think you're holding pretty solid at 60% market share. As far as new patient starts, what proportion are you seeing versus competitor? And have you seen any impact of the five-year GAIL update in November? Have you seen any impact on that, on new patient starts or on compliance?

Thank you, Doug. Good hearing from you. So as a class, we believe that, you know, it's hard to believe that it's still the early days of what can be done for patients with geographic atrophy and of course with the differentiation of our products and the enormous amount of data that we generated including over as you mentioned the full five-year period we are really well positioned to continue to shine competitively I will hand it over to David Atchison to talk a little bit more about market share yeah thanks for the question so you're correct we're holding standing at 60% market share which we're confident in, and we feel really good about where we're coming into 2026.

I can tell you that we're really confident in the competitive strength that we have, including the Gale data that we just talked about and came out this week. I think it's important for us to note that nobody else has that data, and it's a big strength for us to have that kind of data with the patients that are in the long-term study. And our focus, quite frankly, is really being disciplined on execution and to continue to innovate with what we're doing with the brand. and to continue that leadership reinforcement moving forward within the space. So, you know, the market share is part of that, but it's certainly driving innovation is a part that will continue to drive uptake, market growth, and our share growth as well.

Thank you. I would now like to turn the conference back to Cedric Francois for closing remarks.

Thank you very much, and thank you all for your thoughtful questions. We look forward to updating you on our progress, and I believe that we're speaking with many of you later today as well thank you so much and I hope you have a great rest of the day this concludes today's conference call thank you for participating