Apellis Pharmaceuticals, Inc. (NASDAQ:APLS) Q4 2024 Earnings Call Transcript

Apellis Pharmaceuticals, Inc. (NASDAQ:APLS) Q4 2024 Earnings Call Transcript February 28, 2025

Apellis Pharmaceuticals, Inc. beats earnings expectations. Reported EPS is $-0.29, expectations were $-0.37.

Meredith Kaya: Good morning, and thank you for joining us to discuss Apellis Pharmaceuticals, Inc.’s fourth quarter and full year 2024 financial results. With me on the call are Co-Founder and Chief Executive Officer, Dr. Cedric Francois, Executive Vice President of Commercial, David Epperson, Chief Medical Officer, Dr. Caroline Baumal, 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 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.

Cedric Francois: Thank you, Meredith, and thank you all for joining us this morning. As we close out another year, I would like to recognize the progress our team has made. We achieved important milestones in 2024, strengthening our business while navigating some headwinds along the way. Cipher generated over 120% year-over-year US net revenue growth. We presented positive Phase 3 VALION data with EMPHEREZ in C3G and ICF TGF, we advanced our earlier stage pipeline, and we fortified our financial position. Looking ahead, our strategy is focused on three key pillars: First, to transform the treatment of geographic atrophy with cytoplory. To maximize INBATEI’s impact in rare diseases. And third, present our innovative pipeline leveraging our expertise in complement science.

Starting with pillar number one. SIFO3 is the market-leading treatment for geographic atrophy in the US, with more than 510,000 injections administered through December. Recent regulatory developments within the competitive landscape confirm our view that XIFAV is the leading treatment for GA. So a full free unmatched free supplier being labeled, which includes increasing effects over time and flexible dosing, will enable us to further strengthen several of these market leaderships. Over ten. XIFABI has generated nearly $900 million in sales in less than two years, making this one of the most successful launches in recent history. With only two approved treatment options available and no new competitors on the horizon, we are in a strong position.

Our two key priorities heading into the rest of 2025 are to secure set for this leadership and to grow the overall GA market. We are still in the early phases of growth and estimate that only are seen by an eye care professional. Of those, less than 10% are receiving treatment. Building a new market takes time, but we have the right product, strategy, and team to execute. The U.S. is our primary commercial focus for SENTHOVRA, but we will continue to explore select international markets. We were pleased to receive approval from the Therapeutic Goods Administration in Australia last month, and our regulatory review in Switzerland is ongoing. As we continue to focus our efforts on the Safeword relaunch, we are also working to develop the next generation treatment for GA.

To do this, we are combining Salesforce and APL 3000 zero seven parenocyte RNA. This approach is designed to comprehensively block complement activity in the retina as well as the choroid through local and systemic C3 inhibition. We plan to initiate a Phase 2 trial in the second quarter. Shifting gears then to our second pillar, maximizing the impact of empathy in rare diseases. Embraeri continues to elevate the standard of care in PNH. We also look forward to becoming a cedar in nephrology. Starting with the anticipated launch of mPavenient C3G and primary ICF PGN. We recently filed the supplemental NDA based on the positive Phase 3 VALENT data. These results hit the tri-sector with unprecedented reductions in protein, significant clearance of C3 deposits, and stabilization of eGFR.

Q&A Session

Even more compelling was that these results were consistent regardless of disease type, transplant status, or age.

Meredith Kaya: If approved,

Cedric Francois: we expect to launch in the second half of 2025. Our partner Sobi recently received validation of its application, putting them one step closer to making this life-changing treatment available to patients in the EU. In the second half of 2025, we are also planning twenty CHF Phase 3 trials mPavetti in two new nephrology indications: Focal segmental glomerulosclerosis and late graft function.

Meredith Kaya: Now

Cedric Francois: Lastly, our third pillar, our innovative pipeline. We are excited to be advancing the first-ever gene editing approach targeting the neonatal fc gamma receptor with our partner Beam Therapeutics. We look forward to sharing more about this program and our broader emerging pipeline with all of you soon. We are excited about the future of Apellis Pharmaceuticals, Inc. We have two potential blockbuster products, with SyFOVRI and Abavany, a robust development pipeline of clinical and preclinical programs, and a clear path to profitability. I will now turn the call over to David Epperson, our new Executive Vice President of Commercial. I’m sure many of you are familiar with David from previous earnings calls at investor events. And we are thrilled that he’s now using our commercial organization it?

David Epperson: Thank you, Cedric, and good morning, everyone. Let me start with Saffobri. With over 510,000 injections administered and nearly $900 million in net sales, XIFAI has had a remarkable launch. Our focus going forward is to both strengthen our leadership position and grow the overall market. The recent regulatory update from our competitor provides us more confidence than ever in the strength of SYFYRI’s differentiated profile. Three things now are very clear. XIFAVI has consistently demonstrated robust and increased effects over time. XyphoBrid is the only GA product approved for as few as six doses per year. And cyphobri is the only product in a preferred position with many payers. In the fourth quarter, Sifel remained its market leadership with approximately 94,000 doses delivered to physician offices, including 89,000 commercial doses, and 4,600 samples.

Total market share remained stable at over 60% and new patient share trended positively, ending the year approaching 50%. As of December, are more than 2,300 sites of care that have ordered Cyphobri. Cyphobri’s fundamentals remain strong. In the first two months of 2025, we are seeing continued growth in the number of Xyphobia injections administered, which is the true measurement of demand. There are, however, a few temporary factors expected to affect orders of commercial vials and net revenue in the first quarter. First, the overall GA market growth in the quarter has been tempered due to typical Q1 dynamics like Medicare reverifications and winter storms affecting distribution and patient visits. And second, we have also seen a spike in sample usage over the past two months.

We believe retina specialists are using more samples because of a reported funding gap at non-profit co-pay assistant organizations. Samples used in this quarter as compared to the average quarterly sample volume in 2024. The momentum we are seeing in injection demand to date sets the stage for continued growth in 2025 and beyond. Maximizing the GA opportunity will require a long-term and strategic approach. We need to make sure each patient has access to a retinal specialist who can treat them. We need higher utilization from those physicians who are already treating patients with XIPOVRI as well as adoption by retina specialists who may have initially been hesitant to utilize GA treatments.

Meredith Kaya: And we must continue to further strengthen our formulary positions.

David Epperson: Being the only GA product with preferred status provides a significant competitive advantage. We’re executing across key initiatives to achieve these goals, including broadening our reach to the eye care community, amplifying real-world data through key forums, educating payers on Xyphobia’s differentiated value proposition, and connecting with patients through our DTC campaign. We recently launched Phase 2 of our DTC campaign featuring Henry Winkler. This campaign focuses on increasing awareness of GA, anti-foggery, and ensuring GA patients are able to connect to a reno specialist who can treat them. Now let me shift to Empavelli. The commercial and medical teams are ramping up their efforts in anticipation of Empavela’s potential label expansion into C3G and ICMPTEN later this year.

We are in the process of hiring our field-based team, which will allow us to hit the ground running and make a significant impact in the early phases of the launch. Ahead of approval, we are executing several prelaunch activities focusing on disease state awareness. These include participation in key nephrology conferences, building relationships with key physician accounts, KOL and payer engagement, and patient education. These activities maximize the likelihood of a successful launch in C3G and ICMPGN. They also reinforce our commitment to rare nephrology with our programs in BGF and FSGS.

Meredith Kaya: The commercial opportunity is significant with an estimated 5,000

David Epperson: C3G and ICM PGN patients in the US. Empavelli is the only drug to be studied in a broad patient population. Given the strength of the Phase 3 data, we believe mPavili will be used across all patient groups and disease severity. Physician feedback has been consistent that treatment choice will be based on efficacy over the route of administration given the severity of C3G and ICMPGN,

Cedric Francois: Many patients, even those with mild to moderate disease,

David Epperson: will eventually suffer kidney failure. In PNH, Amphibelli generated approximately $23 million in U.S. net product revenue in the fourth quarter. Compliance rates remain high at 97% and the safety profile remains consistent with our previous updates. We expect continued competitive pressure in 2025, but this should be more than offset by initial revenue generated from C3G and ICMPGN. With that, I will now turn the call over to Caroline.

Caroline Baumal: Thanks, David, and good morning, everyone. I’ll start with Syphovari. We continue to see evidence supporting Syphobri’s strong efficacy and consistent benefit to GA patients over long periods of time. Earlier this month, we presented 48 months of data from our GALE extension study. That’s reinforced Xyphobia’s increasing effects over time. These data demonstrated that early treatment with Xyphobia leads to preservation of retina tissue at magnitudes of approximately 1.5 disc areas on average at 48 months in noncipobial GA patients dosed monthly. For context, 1.5 disc areas is the size of approximately two phobia areas, which is considered highly meaningful by retinal specialists. We are also beginning to see real-world evidence of the benefits of cystovarity treatment.

An independent analysis of real-world data concluded that by month nine of treatment, Cyfovary reduced the annualized growth rate of GA by over 40%. Separately, another analysis of real-world data following cyphovretreatment showed stable visual acuity over multiple injections. While there are always limitations to independent analysis, these results add to the extensive clinical dataset for Cyphobri and strengthen confidence in its treatment benefit. As Cedric mentioned, we are also developing a next-generation treatment for GA. We believe combining SifuVri and our siRNA APL 3000 and seven may provide comprehensive complement blockade in the retina and in the choroid. Specifically, SYKOVRI inhibits complement in the retina and APL-3000 and seven is intended to target systemic complement activity in the eye.

With less C3 present in the eye following a higher degree of efficacy contribution from SYKESOVERAGE. Last month, we shared Phase 1 data with EPL-3000 and seven in healthy volunteers showing greater than 90% knockdown of C3 products as measured by the remaining levels of protein in the blood. We expect to initiate a Phase 2 study with Xifonfri and APL-3000 and seven in GA patients in the second quarter. Shifting to Empovelli. The Phase 3 VALANT results provided further confidence in ImpeLE’s ability to control complement and provide a meaningful difference to patients with rare kidney diseases. Based on these data and a strong rationale for complement inhibition, we plan to initiate two pivotal studies with Empavelli in the second half of this year.

One in primary focal segmental glomerulosclerosis or FSGS and one in delayed graft function or DGF. The complement pathway plays a significant role in both diseases and there are currently no FDA-approved therapies. SSGS is a rare kidney disease that causes scarring of the glomeruli. Similar to C3G and ICMPGN, FSGS results in end-stage kidney disease within five to ten years for approximately half of patients. There are an estimated 13,000 primary FSGS patients in the United States. DGS is a complication in kidney transplantation where the transplanting kidney fails to function and typically requires dialysis within the first week of transplant. This negatively affects the long-term survival of the kidney and overall patient outcomes. In 2023, there were an estimated 21,000 transplants in the US using deceased donor kidneys.

DGS occurred in 30 to 35% of these transplants. FSGS and DTF were chosen due to their high unmet need, significant complementary involvement, and our ability to move directly into pivotal programs with potential approvals by 2030. Given our leadership and expertise in complement, we are uniquely positioned to bring treatments to patients with these devastating diseases.

Tim Sullivan: I will now turn the call over to Tim for a review of the financials.

Caroline Baumal: Tim?

Tim Sullivan: Thank you, Caroline. I will now provide an overview of our financials. Additional details are available in the press release that we issued earlier this morning. Total revenue for the fourth quarter of 2024 was approximately $13 million, including $168 million in CyphoVre and $23 million in Empto Valley, US net product revenue. Total revenue for the full year 2024 was $781 million, a nearly 100% increase as compared to 2023. Turning to the rest of the P and L. For the fourth quarter, cost of sales was $40.9 million, R and D expenses $76.4 million, SG and A expenses were $121.5 million, and we reported a net loss of $36.4 million. Regarding Ciprovery, gross to net remained stable relative to the third. We anticipate gross to net to be in the low to mid-twenty percent range through 2025.

We took a 1% price increase on January first that is intended to help offset some of the ASP erosion while managing customer reimbursement. We continue to execute against our strategy while maintaining financial discipline. We made strong progress from a financial perspective in 2024. As you can see on Slide seventeen, our total revenue in 2024 nearly matches our non-GAAP expenditure. With $411 million in cash and cash equivalents at the end of 2024, we remain confident in our financial position. We anticipate operating expenses in 2025 to be relatively stable compared to 2024. We expect our existing cash combined with our future product sales to be sufficient to fund our core business to profitability. I’ll now hand the call back over to Cedric for closing remarks.

Thanks, Tim. We have started 2025 from a position of strength

Cedric Francois: and are focused on building on the success of Cipher, preparing for our second commercial launch with EMPAVETI in C3G and ICMP, progressing our pipeline, and solidifying our financial position. By doing this, we remain confident in our ability to create significant value for patients and shareholders over the coming years.

Meredith Kaya: Please standby while we compile the Q and A roster.

Cedric Francois: And our first question

Meredith Kaya: will be coming from

Jon Miller: John Miller of Evercore ISI. Your line is open.

Jonathan Miller: Hi, guys. Thanks so much for taking my question and congrats on all the progress.

Cedric Francois: One on emphysema and the kidney indications, I guess, and a quick follow-up on that. Obviously, your primary endpoint showed really great results with the spot test and new ACR, but the competitor had a 24-hour endpoint. I know you said in the past that you looked at 24 hours, but we haven’t seen it yet.

Jonathan Miller: Do you plan on presenting that publicly? I assume it was included in the submission to the FDA. Do you have a sense of which metric the FDA is most focused on? Some commentary, that would be great. Hi, John. Thank you so much for that question. So that we’re very excited about. The submission with AMPAVITY, of course, and looking forward to feedback in short order. The 24 hours was consistent with what we saw with the spots but the endpoint, of course, was the spot. Think what is really important here is not just the proteinuria, right, but the consistency that we had across all the phenotypes of this disease and across all kind of three important metrics that exist. There is, of course, a protein area, which had such a highly clinically meaningful reduction we also had the EGFR stabilization.

And in addition to that, and I cannot overemphasize that, the impressive results on the histo pathology. Right? I mean, so when you look at these kidneys, you see the c three deposits go away. You know? Melting like snow in the sun quite frankly over the course of a couple of months. And after six months, as much as 70% of patients have no more detectable c three deposits. So that’s something really important to bear in mind. We’re excited about the submission, about what we can do for And submission of our publication will come out soon as well. Alright. Thank you. Maybe just as a quick follow-up, given recent news coming out of the agency, I’d love to get a sense of your confidence level that you’ll be able to launch in the second half of 2025, that the agency will be able to meet its PDUFA requirements, and you’ll get a timely review.

Yeah. So of course, we have no control over macro, but at the current point in time, there is no indication at all that’s if there is any type of delay.

Jonathan Miller: Thanks so much.

Meredith Kaya: Thank you. And one moment. For our next question, Our next question will be coming from Tazeen Ahmad of Bank of America Securities. Of America Securities. Your line is open, Tazzy.

Tazeen Ahmad: Great. Thank you. Good morning, guys. I have a couple of questions regarding size ovaries. So just based on the metrics that you’ve cited or really trends in the first quarter. How should we be thinking about results in the first quarter relative to four q? It be that sales would be lower this quarter for the reason that you mentioned? And then regarding the beneficial status in Medicare Advantage Do you think that that’s gonna have an early and noticeable impact on new patient share in the year, or do you think that’s something that would happen more gradually? And then I have a follow-up. Thanks.

Cedric Francois: And hand it over to David. Hey, Tasim. It’s David. Hope you’re doing well. Thank you

David Epperson: you for the question. So like we talked about in the in the call, some of the things that we’re seeing in Q1 are transit impact to what we think will, impact net revenue, And while they are, you know, anticipated to be temporary, we do think that Q1 will be lower than q four as a result. And we’re not gonna guide on anything for q one beyond that. But that’s that’s where we are currently least with with what we’ve seen so far. Oh, it’s it the other thing to note too, by the way, is one of the things that is is really positive for us is that the good news we’re seeing injections which we talked about in the in the call as well, grow in q one versus q four. Which is is very positive for us. And we expect so is that you know, once we get somebody’s temporary Impacts against the q one numbers out of the way. We should see and continue to see and expect to see 2025 to have growth.

Tazeen Ahmad: Okay. And then my follow-up is about the label change that was made, for the competing product. How important is it that the label for iSurvey will say monthly in injection relative to every other month? Because it does seem based on our doc track that up until now, Docs seem to have adopted every other month. Do you think that that practice will change?

David Epperson: Yeah. So, look, I I think it’s a little bit early here, right, in regards the label change. I think there’s still some things here that that folks are still trying to figure out. I will tell you, myself and Caroline, which I’ll hand to in a second for some comment, we were at the Maculus Society when this came out, which is a prestigious meeting that’s held in Florida. And the general talk and discussion was around site vote rate. And the every other month dosing. I think the more important part was to follow on to that, which is we had a lot of robust data that was presented at that meeting. That really helped us to solidify even further that Cigna’s consistent increased effects over time is gonna have impact And is it having impact?

That was a lot of the discussion. Plus, we’re the only product that is can be treated, and it’s in the label for as few as six doses a year. And we’re the only product that has preferred positions with payers. That was a conversation in Maccles Society. So, I’ll hand it over to Caroline for additional comment.

Caroline Baumal: Thank you. Hi, Tazeen. You know, what I hear from my colleagues and what I know from being a physician is that efficacy and convenience are really important driving factors for for patients, physicians and payers. And we have consistently demonstrated efficacy with every other month dosing. This has not been demonstrated with iServe in a clinical trial.

Tazeen Ahmad: And

Caroline Baumal: you know, the FDA did not approve them for every other month’s dosing. So our label includes all of our benefits, our efficacy efficacy, increasing effects over time in a flexible dosing regimen that includes monthly and every other month dosing.

Meredith Kaya: One moment for our next question. Our next question will be coming from Anupam Rama of JPMorgan. Your line is open.

Anupam Rama: Hi. Thanks for taking the question. This is actually Malcolm

Cedric Francois: last several months and their updated label, what are you hearing from payers on the potential for preferred tiering for a Cytobera?

David Epperson: Yep. Welcome. Thank you. It’s David. Thanks for the question. So we’re really fortunate to have a number of payers and sizable plans that have us in a preferred position. I think it’s a little hard to forecast what that looks like. But I will tell you, when we look at and have conversations with the payers, it really comes down to every other month dosing, the fact that we have it in the label with the efficacy that matches up to that. So those those are the things to keep in mind. And we’ll see what happens in the future, but I can’t really predict what’ll happen moving forward with the payers. At least at this point in time.

Anupam Rama: Great. Thank you.

Meredith Kaya: Thank you. One moment for our next question. Our next question will be coming from Salveen Richter of Goldman Sachs. Your line is open, Salveen.

Salveen Richter: Good morning. Thanks for taking my question.

Cedric Francois: Could you give us a little bit more color on how we should think about the cadence of the SYFOVRI launch year in 2025, just given that the commentary on 1Q being lower than 4Q, but there’s growth in 2025 and also in the context of you know, a potential label update for a survey and and the formulary status and and expansion ex US. Thank you.

Cedric Francois: Thank you, Saline. So I think first of all, really important to bear in mind. Injections continue to grow. Right? And that is a reflection of the unmet need in this disease. Remember, fewer than 10% of patients with geographic atrophy have been treated and only about half of patients are currently being seen by accurate professionals. The opportunity there to do good for patients and to generate revenue is enormous as it has always been. So that is as far as the overall market is concerned. Competitively, quite frankly, I think we are in an enviable position right now. You know, last year, of course, we went through several motions. But at the end of the day, I think it’s important to bear in mind that the CRLs for our competitor, you know, beyond whether it’s resolved or not now, really called out the shortcomings that our competitor has most notably the fact that there is or that there was a twelve-month limitation initially which a lot of physicians did not know.

And then, of course, also the lack of data for every other month dosing. So I think it was important to kind of level set the knowledge around two products so that physicians can take the right decisions. So we’re very excited about where 2025 is heading. And beyond as well.

Meredith Kaya: Thank you. And one moment for our next question. Our next question will be coming from Yigal Nochomovitz of Citigroup. Your line is open.

Yigal Nochomovitz: Hey, Cedric and team. Thanks for the question. I had a question on the combo trial with o seven and cifobri. How are you thinking about the phasing of the dosing there?

Cedric Francois: Given the intravitreal and the systemic

Yigal Nochomovitz: are you gonna interweave them? Or can you just talk more about the strategy for that combo dosing? And then will this phase two have any

Cedric Francois: comparison arm or is it just gonna be a single arm study? Thank you. Thank you so much, Yigal. So we’re super excited about our three zero zero seven program. And you are asking as usual, an excellent question, which is we stopped carefully to how to implement this in a physician setting. Right? So the idea there is that with a subcutaneous ejection, if you lower the systemic levels of c three, So turning off the faucet if you want, and you give a stoichiometric advantage so dosing advantage. To say, Fulvary, which you still need NDA. To control the enzymatic activity of the complement cascade We will synchronize those injections to every two months and every three-month administrations both of which so the intravitreal and the subcutaneous, both of which would happen in the physician’s office.

So I think that’s something really important. There will be a dosing component to this as per usual so that we can explore those two separate cosologies. You know, in the broader strategic context, I mean, we’re looking forward to this year to you know, growing the market in GA. Truly establishing ourselves, you know, as as we are the market leader, but growing that share that we have and then also to what we subjectively, of course, but I believe will be one of the, if not the most exciting developmental program geographic atrophy by the end of this year and into 2026.

Yigal Nochomovitz: Thanks. And maybe one for for Tim. Just on Empavelli, obviously, you have a a ton of really interesting larger indications coming down the pipe. As you’ve alluded to, the C3G, the

Cedric Francois: CCMB MPGN, FSGS potentially, GF FVAGF. So you know, as far as the patent looks like, do you have any comments on how you might Extend that. Even further given given the potential for

Tim Sullivan: a very significant revenues on these follow-on indications. Yeah. Sure. If I heard you correctly, you asked if there was a way to kind of extend our exclusivity. Is that I understand that from a patent perspective?

Yigal Nochomovitz: Yeah. So Mhmm.

Tim Sullivan: If we have composition of matter through kind of 2033 ish and 2035 with customary extensions. So yeah, that’s still pretty reasonable runway for the indications that we discussed and we just discussed that those you know, those are both chosen because we believe that we would have, you know, the ability to launch those with a significant amount of patent life left. Now there are other things that we have in mind. We also have, as Cedric mentioned, some combination product work ongoing that could really change change our the profile of our systemic administration of, pancreatic colposals. So we’re looking at life cycle cycle management initiatives as well. From a composition matter perspective, 2035 is really is really where that runs out.

Yigal Nochomovitz: Okay. Gotcha. Thank you.

Meredith Kaya: One moment for our next question. Our next question will be coming from Colleen Kozy of Baird. Your line is open, Colleen.

Colleen Kusy: Great. Good morning. Thanks for taking our questions. Congrats on the progress. So you had some strong momentum on the payer front last year. Can you put into context what what percent of the market you have preferred positioning in and how much more growth on payer front do you expect to achieve in 2025?

Cedric Francois: Thank you, Colleen, and good to have you back. So I’m gonna hand it over to David.

David Epperson: Hey, Colleen. Good to hear from you, and thanks for the questions. So we’ve got some big plans, like Aetna is a great example, that as of January first, has us in a preferred position in patient has to start with Cycobri before they could move to the competitive product. There’s some big plans that are out there. I think percentage wise, it’s a little bit hard to to talk through that because there’s so many intricacies in the plans on how they actually look at this. And downstream accounts in particular to the PBMs can make their own decisions on on what they wanna do with that. So but I will tell you, we have a number of sizable plans and two major PBMs that have us in a preferred policy position for their downstream accounts to make those decisions on.

Colleen Kusy: Great. That’s helpful. Thank you. And then for C3G and ICMPGN, have European regulators and US regulators historically approach that review similarly? Since we’ve seen some positive momentum on the European opinion front, just wondering how that decision might have read through to the US review.

Cedric Francois: Yes. So it was thank you so much for that question, Colleen. So our partner, Sobi, and and have been in lockstep through all of this. And, you know, we’re we’re very excited about the global deployment of in Bavarian, the US and as far as ex US, of course. I think what’s again, kind of highlighting what we’ve mentioned many times. In the US, for example, we estimate there are approximately 5,000 patients We estimate and we believe that we will only be competing with you. Only other product, should it be approved and maybe on the market better than we get there? For about a thousand out of those 5,000. So it’s a it’s a really special opportunity for us, and the numbers quite a bit higher than 5,000. Really unique opportunity that deserves the prioritization that it gets within our base as well as with our partners. So

Colleen Kusy: Great. Thanks for taking our questions, and congrats on Braga.

Meredith Kaya: Thank you. One moment for our next question.

Phil Nadeau: Next question will be coming from Phil Nadeau of TD Cohen. Your line is open.

Phil Nadeau: Morning. Thanks for taking our questions.

Cedric Francois: First, a follow-up and a and another question. The follow-up is on your comments you made about the sampling. Can you go in a little bit more detail on the dynamics of why there’s a funding shortage and gives you confidence that that this is a q one issue and it it won’t persist later in the year?

Cedric Francois: Sure. Thank you so much, Phil. So look, the the settling are reflection of a couple of factors. But one that stands out is what we spoke about before, which are these organizations. That provide supports to physicians to you know, help with the co pay of of the product. Is not just for SAFEIVO re, but for all intravascular injections, And it’s important to note that we do not have real visibility on you know, how this is managed. This is by design that is should be appropriately independent organizations. Determine how they manage their fundings. So we contribute, others contribute. We typically contribute at the beginning of the year, but it can happen throughout the year from other organizations. It has happened before that they ran out.

So what then typically happens is that physicians will go towards sampling to be able to still take care of those patients. Right? So I would say that the increase in samples is a reflection of the fact that these patients are in need. There is a, hopefully, and then by all expectations, temporary funding gap The physicians compensate for that with template.

Phil Nadeau: Got it. That that is helpful. And then, broader question on MPovelli and C3G and ICMPGN. In the slide deck, you outlined four buckets of patients, and with that that disease. Can you talk about how you’re gonna focus Your marketing, for example, will you focus on post transplant patients where you’re likely to be the only option Or are there other other elements or physicians that you think are highest priority?

Cedric Francois: Yeah. Well, thank you so much, Phil. So you know, again, I think you something that we’re particularly proud of, which is that when we studied these diseases, we went very broad. Right? We said we’re gonna study C3G as well as BGN, which are split about fifty fifty. In the population that we are targeting. We looked at pre transplant, but also post transplant, which is a segment that often gets neglected. We studied pediatric patients as well as adults. And we studied, you know, what happens in these diseases sometimes C3 is depleted, sometimes it’s not. We studied everything, and everywhere we saw a consistent response far as you know, the the the impact on the disease was concerned. What that means moving forward, because I think what you’re asking is is where is kind of the where are the initial Demographics, I think the post transplant segment is a particularly interesting one.

I think it’s also worth noting that within this small community of transplant nephrologists, and Parete is taking on quite a pristine reputation, not just because of the data that we had at Valiant, But also because all of the recent xenotransplants so you may have seen in the news, the kidney transplants that are happening from genetically modified pigs. You know, our transplants that were either rescues or are now, in all cases, as far as we know, proactively being you know, protected with empathy. So the I’d say the the reputation of EMPHEREVITY to be able to control complement within the kidney is growing steadily and something that, of course, bodes well for our launch later this year.

Phil Nadeau: That’s very helpful. Thank you.

Tim Sullivan: Thank you, sir.

Meredith Kaya: One moment for our next question. Our next question comes from Akashtawari of Jefferies. Your line is open.

Katherine Wang: Hi. This is Cathy on for Akash.

Cedric Francois: So on a sales of earning call, they stated that Docs were essentially warehousing patients and pausing their I survey doses. Until the 24-month label update rather than switching them to Sysovri. And then as such, they were expecting a bolus in March once dosing resumes. So given that, I their previous label got updated a couple weeks

Katherine Wang: before the PDUFA with the two-year data on the label,

Cedric Francois: but without every other month dosing. What are you seeing in terms

Katherine Wang: of Sifobri versus ivermectin usage in the past few weeks? And then

Cedric Francois: what should we expect regarding Dynamics on Cyphero three versus iSurvey going forward? And then what do you think your team needs to do to change, doctor’s perception?

Katherine Wang: Thank you.

Cedric Francois: Yep. So I think I will answer the first part, and then I will hand it over to Caroline. To talk about doctor perception, which of course is very important. But I think look. There may have been some warehousing with certain physicians, with certain patients. The take home very clearly here is that we are definitive market leader and we are growing SaaS leadership. That is very clear from all of the intelligence that we have internally. At Aperis, and that’s something that you know, is rooted in the data that we have. Right? So I think that is the key message for us, and I’ll hand over to Caroline to talk about how physicians can review the voice.

Caroline Baumal: Thank you, Cedric. Well, we we hear a lot from our physician colleagues who just attended three major meetings, most recently the MACIUS Society. And physicians are very enthusiastic about our differentiated efficacy data and our long-term data. I mean, we presented tissue saved and how much tissue that was that was over a disc and a half. Of, retina tissue that’s saved with psycho overuse, and we presented long-term data Patients who’ve been treated with sulfobri for 48 months. So this is really unprecedented. And this is the key driver amongst physicians. I think that It In the end, that position is really speak to the scientific data, and it’s very meaningful for them. Okay. Understood. Thank you.

Katherine Wang: And then just like a super quick follow-up, It seems like, like, could you provide some more color on inventory in q four? Because it seems like quarter over quarter sales growth was about 10%

Cedric Francois: versus Vyle growth was about 5%. But you mentioned that you had stable gross to net dynamics. Thank you.

David Epperson: Yep. This is David. So thank you for the question. Coming out of Q4 and usually you’ll see in any given quarter, at the end of a quarter, some move in regards to orders that that will move inventory a little bit. We saw a little bit of course, you know, coming out of q four, and sometimes you’ll see a little bit more around the holidays. But it did not put us in the situation that we were out of the typical two to three-week range that we have. And, we may see a little bit of drawdown you know, in the front of q one, but for the most part, it was not a significant number that we, we could concerned about anyway.

Katherine Wang: Got it. Understood. Thank you.

Meredith Kaya: Thank you. One moment.

Katherine Wang: For our next question,

Meredith Kaya: Our next question will be coming from Ellie Merl of UBS. Your line is open, Ellie.

Eliana Merle: Hey, guys. Thanks for taking the question. In terms of GA, I guess, what’s the latest that you’re seeing in terms of patient adherence and what you’re seeing in terms of any discontinuations, I guess, sort of how we should be thinking about long term, what the discontinuation rate or compliance on therapy might be. And then just a second question, in terms of your expectations for the number of samples beyond one q, I guess, what do you expect in terms of this dynamic in two q on the rest of the year? Did you mention this was temporary funding gap in the patient assistant organizations. But just curious what you expect over the course of the year in terms of the number of samples. Thanks.

Cedric Francois: Yes. Thank you so much, Ellie. So first of all, as it relates to the difference, you know, we actually see adherence levels for SAV four really be similar what we have or what you find. With. Which is, you know, a a very positive trend considering that NFHS is kind of more viewed as the acute treatment with the immediate benefits, whereas I foresee as we all know, you make an investment in the future protection you know, the this these large amounts of tissue that you can preserve if you are faithful to the product. So that is something that are have no concerns around. As it relates to the samples, I will have to answer that. Yeah. So I think a couple things. And just remember upfront,

David Epperson: I think it’s important to remember that samples being requested and put into a patient for treatment is a sign of demand, which is very positive for us. And we’re seeing the injections increase in q one versus q four. So we we feel good about that. I think a couple things. First of all, we believe this is temporary, and we anticipate that, you know, these issues that we’re working on that samples are being used in place of a commercial product will be fixed over time. We don’t know what that looks like as far as timing. And the funding gap and when all of those things kinda come together that Cedric mentioned, it’s really it’s in the control of of the groups that that manage this with patients and with physicians. So we really don’t have an answer to that. But we will continue to supply samples if needed. And and put patients, you know, in a place where they can be treated.

Eliana Merle: Got it. Thanks.

Meredith Kaya: Thank you. One moment for our next question. Our next question comes from Annabel Samimy of Stifel. Your line is open, Annabelle.

Annabel Samimy: Hi. Thanks for taking my question.

Cedric Francois: So I’m just trying to understand the competitive dynamics a little bit.

Annabel Samimy: Better for Syscovery acute.

Cedric Francois: Help us square away comments about leadership position of greater than 60% share, but then new patients is more like fifty fifty, and then we’ve got

Annabel Samimy: you know, competitive headwinds coming from the label expansion, but then you

Cedric Francois: talk about positive trends in injection growth, preferred formulary status, and positive feedback that you’re getting from the community around escharci and plex flexibility of Cifovre. So

Annabel Samimy: I guess maybe you can help us really understand what that competitive headwind

Cedric Francois: is

Annabel Samimy: that that is pushing the new patient share to fifty fifty.

Cedric Francois: Because it looks like everything’s sort of lining up well for SifoRev, but I’m not

Annabel Samimy: Sort of.

Cedric Francois: Able to square away why it’s still fifty fifty for the new patient share. Yeah. Thank you, Annabelle. I think look. We’ll see, you know, where where it ultimately will end up, of course. Right? I mean, where but the direction is positive for us. Right? So but I think most importantly, Even a couple of months ago, I think, you know, we were in a competitive situation where the the data or the knowledge around our com our competitor was, I would say, weak in the retina community. As far as it relates to what does this drug actually do. You know? What does it do in the long run? Lot of physicians, as I mentioned, didn’t know that this drug was only approved initially for a one-year period, so that was called a you know, a lack of surprise. So I think that they’re know, we are now playing in a level playing field and a level playing field the differentiation on efficacy It’s

Caroline Baumal: know,

Cedric Francois: Incredibly robust. Right? And that is being recognized by retina doctors. And that’s not just On the magnitude basis, it is also on the longitudinal data. And I would say that it’s a real turning point for us know, then we’re looking forward to to working from. Don’t know, Caroline, if you want to add something.

Caroline Baumal: Well, I think one of the things that really differentiates us with physicians is the every other month dosing. And, you know, we use clinical studies to guide us. And The

David Epperson: oh,

Caroline Baumal: So best data we have that the heterogeneous broad patients that were studied all show the demonstrate the efficacy into year four With every other month dosing, which will just increase the convenience and help patients stay compliant. So, I mean, physicians continually come up to me We’re grateful for what we’re presenting. And and show that this long term and every other month those things speaks to their patient population. Okay. Great. And if I could just ask a question on C3G, MPGN launch. What are your expectations there? You know, you’re not so Walter is clearly gonna mess him out a little bit earlier, but you did mention that physicians are a little bit more focused on or or a lot more focused on efficacy. But I’m curious the the level of urgency patients have to get on treatment. And so we can what can we expect for, I guess, an early launch trajectory for for that product?

Cedric Francois: Yeah. Thank you, Annabelle. I think the key thing is that we we see demand in in the request that we already get for capacity use and expanded use access. Right? So demand is fairly important. Remember, these are younger patients, about half of whom over a ten-year period, which is not a lot when you’re twenty, right, or thirty. A fifty percent is the chance of losing their kidneys. So the need is incredibly high. And, again, I want to emphasize that You know, based on the data that we have, we will probably be competing probably only for about 20%. Of that overall bucket of patients. So a really important opportunity for us and for patients.

Annabel Samimy: Okay.

Cedric Francois: Great. Thank you.

Meredith Kaya: Thank you.

Meredith Kaya: One moment for our next question. Our next question will be coming from Douglas Tau of H. C. Wainwright. Douglas, your line is open.

Douglas Tsao: Hi. Good morning. Thanks for taking the questions. First question I had was in terms of the SERNA plus type of products, Cedric. I know in the past, you’ve spoken about Cypher over having a very powerful effect on preservation of photo photoreceptors and less so on RPE cells. And so I’m just curious with this approach, is this sort of what you’re specifically by going after the Chloric, which isn’t which is sort of adjacent to to to to the RPA as well.

Cedric Francois: Well, Doug, I’m very impressed with that question. You are correct. This is so the the impact that size forty has on the form photoreceptors

Douglas Tsao: You know, it’s

Cedric Francois: near perfect. Right? About a hundred percent when you look in the first six months. I mean, it is it’s incredibly robust impact on those photoreceptors. The RPE cells are the ones that continue today, of course, of course, meaningfully slow down. And then the question that we’re trying to answer here is since if we on the choroidal side, right, on the back of the eye, if we can lower c three levels, will we be able to impact RPE cells in a way that is similar to the photoreceptors? So excellent question and the answer is yes.

Douglas Tsao: Okay. Great. And if I just a quick follow-up for David. Just I’m curious, you know, to the extent that you anticipate seeing an impact on the Medicare redesign for this year. Or if you can qual you know, sort of quantify it at this point. Okay. Thank you for the question. I I think quantifying that is is challenging. For us, and I wouldn’t hate to take a guess at it, So it’s something we’re looking at. We’ve got a whole team, of course, that manages all the things. We do with payers, especially in our space with CMS, but I don’t think I can quantify that at least at this time. Okay. Great. Thank you so much.

Cedric Francois: Yep.

Meredith Kaya: One moment for our next question. Our next question will be coming from Joseph Stringer of Needham and Company. Your line is open, Joseph.

Joseph Stringer: Hi, good morning. Thanks for taking our questions. Two from us.

David Epperson: Just wanted to get your updated commentary on any On the switching dynamics between Cyphobia and Iservay, secondly, I know prior question asked about Advanced rates. But just curious, what about compliance rates for DIPROVRI? For example, patients missing or skipping injection. How does that look or how is that changed over time? Thank you. So so this is David. Thank you for the question. Couple things, I think Cedric and Caroline touched on already some of the compliance where we fall with Cytiv OBRY. And it’s about in the same range as anti VEGF. So actually, I feel good about that because for us to be in the the GA treatment area with something that’s that compliant, I think it’s it’s very positive because it is a disease opposed definitely slower than than, wet a m d.

As far as the far as the question on the dynamics of switching, so, you know, we look at this on a regular basis. I will tell you that we’ve had a number of weeks, especially during the CRL period that they had for the competitive product that we saw a number of switches. And I still think we’re seeing that today. In the first part of the front end of q one. And the good thing is and I think what’s driving my thinking around that is the fact that we are seeing an increase in injections in q one versus q four. And I think that we’re we’re in a good place to see growth overall in 2025.

Meredith Kaya: Moment for our next question. Our next question will be coming from Lachlan Hanberry Brown of William Blair. Your line is open.

Lachlan Hanbury-Brown: Hey, guys. Thanks for taking the question. I wanted to ask more about the efforts

Cedric Francois: you’ve made to get doctors off the sideline. You know, you’ve said that the sort of shift towards the efficacy focus focused messaging is resonating well with physicians, but I’m wondering if you can sort of translate that into any changes of actual prescribing behaviors or or new prescribers. Yeah. So that is that is what we are seeing. And thank you for that question. I think what is what is gratifying after, you know, three years of launch now is that the data becomes very clear. Right? We have the extension study. The data becomes you know, much more concise. To communicate and, you know, to main message at Magdalena Society, which is one that I think really resonates the most, is that if you are on four years of treatments, with Xytoberia, could have up to three square millimeters of retina preserves.

Right? Three square millimeters of retina is one and a half dyskerias. A huge amount of real estate in the back of the eye. That is you know, when you tell physicians that it resonates incredibly well, is the reality of this drug and one that we cannot really use moving forward. Safety situation is very stable, and efficacy is becoming the brand focus. Got it. Thanks. And and a follow-up, if I may, sort of following up on Yigal’s earlier question on on patent life for Ampere Valley. Curious if you can give any color on what you had assumed for IRA price negotiations when you were doing the sort of business cases for FSGS. And DGF. You know, I realized there’s probably still more questions than answers there, but just would be great to get real thoughts on sort of what you’d assumed Thank you so much.

So these are look. We did a thorough analysis after the readout of Valiance. In the kidney based on the premise that we have clearly exquisite target engagements. In the kidney in the glomerulus. And we did the usual work that you do in that situation, the competitive analysis. The biology, what can you do with the patent life of the drug, and that is where these two DCC merge. So much more will follow. We’re excited about these indications and what we sent to conditions.

Meredith Kaya: And one moment, Tess. One moment for our next question. Our next question will be coming from Ryan Deschner of Raymond James. Your line is open. Right?

Ryan Deschner: Hi. Good morning, and thanks for the question. Have your expectations, for gross to net in 2025 and it and it steady state evolved at all in the last few months? And can you give us any more detail on what you’re expecting to see in terms of timing and duration of the impact of the new DTC campaign on in 2025 and beyond. Based on what you saw in the prior campaign. Thank you.

Tim Sullivan: Yeah. Thank you very much for the question. I’ll take the gross net piece and hand it over to David for the impact of the DTC. So we we the simple answer is no. Our our our

David Epperson: Human gross to that hasn’t changed at all.

Tim Sullivan: At the end of the third quarter, we did guide to low to mid-twenties throughout the course of 2025 and that that remains the same.

David Epperson: And, David, Yep. Thank you, Tim. So I appreciate the question on DTC. It’s a little early. We started running that commercial on television with Henry Winkler in mid-January. But I can give you one piece of information that happened that that’ll give you an indicator of some of the early impact that we can see. We did have the commercial run during the Saturday night live fiftieth anniversary special with about fifteen million views on the commercial. Which was attributed to driving about three thousand visits to our website. At that time. So we can see things like that early. It’s gonna take time for us to see the total impact you know, throughout the next several months.

Ryan Deschner: Excellent. Thank you very much.

Meredith Kaya: And we do have time for one more question. And our last question will be coming from Derek Achchila of Wells Fargo. Your line is open.

Derek Archila: Hey. Good morning, and thanks for taking the question. Maybe just two for Tim. I guess, how should we think about you know, OpEx growth in 2025 relative to 2024? You know, is there gonna be a lot of growth coming from, you know, some of the R and

Tim Sullivan: d initiatives that you guys talked about? And just, you know, based on some of the seasonal factors

Derek Archila: in one q and the sampling, I guess, how should we be thinking about gross margin trends through 2025? Thanks. Sure. So from the perspective of OpEx versus 2024, we said in our prepared remarks that we expect those to be more or less the same I think that’s probably the case when you think about what we’ve some cost savings from our European infrastructure, some of which we scaled down. Will be offset by some R and D expenditure that gets increased And and then from the gross margin perspective, you know, we we we don’t guide on that. There are a lot there’s a lot that goes into gross margin that’s sort of moves around. But from a sampling perspective, you know, I think we gave you everything we could from the perspective of color on how we project that. We really don’t have any visibility. What we do know what we did talk about is that we see, you know, an approximately 5,000

David Epperson: know.

Tim Sullivan: Vial estimated increase of samples in this quarter And so doing the math on that, you can kinda get to a reasonable idea of what our

David Epperson: our revenue is per vial. You can understand what that would be

Tim Sullivan: And, frankly, that’s

David Epperson: No. That’s

Tim Sullivan: That’s the piece that we could, right now, kind of get into our our gross margin impact in in the first quarter, at least as an s Beyond that, we really have no visibility, unfortunately.

Derek Archila: Got it. Thank you.

Meredith Kaya: And I would now like to turn the call back to Cedric Finshwa for closing remarks.

Cedric Francois: Thank you so much, and thank you everyone for joining us this morning. If you have any follow-up questions, please feel free to reach out to Meredith. You so much.

Meredith Kaya: And this concludes today’s conference call. Thank you for participating. You may now disconnect.