TVTX - NASDAQ

Good afternoon, and welcome to the Travere Therapeutics Fourth Quarter and Full Year 2024 Financial Results Conference Call. Today's call is being recorded. At this time, I would like to turn the conference call over to Victoria Prescott, Manager of Investor Relations. Please go ahead, Victoria.

Thank you, Cloy. Good afternoon, and welcome to Travere Therapeutics Fourth Quarter and Full Year 2024 Financial Results and Corporate Update Call. Thank you all for joining. Today's call will be led by Dr. Eric Dube, our President and Chief Executive Officer. Eric will be joined in the prepared remarks by Dr. Jula Inrig, our Chief Medical Officer; Peter Heerma, our Chief Commercial Officer, and our Chief Financial Officer. Dr. Bill Rote, Senior Vice President of Research and Development, will join us for the Q&A. Before we begin, I would like to remind everyone that statements made during this call regarding matters that are not historical facts are forward-looking statements within the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements are not guarantees of performance. They involve known and unknown risks, uncertainties, and assumptions that may cause actual results, performance, and achievements to differ materially from those expressed or implied by the statement. Please see the forward-looking statement disclaimer on the company's press release issued earlier today as well as the Risk Factors section in our Forms 10-Q and 10-K filed with the SEC. In addition, any forward-looking statements represent our views only as of the date such statements are made, February 20, 2025. and Travere specifically disclaims any obligation to update such statements to reflect future information, events, or circumstances. With that, let me now turn the call over to Eric.

Thank you, Victoria, and good afternoon, everyone. We just completed a remarkable year, one marked by execution, innovation, and a relentless commitment to patients with rare kidney and metabolic diseases. Our exceptional progress culminated in the full FDA approval of FILSPARI for IgA nephropathy in September, a major milestone for our company and the patients we serve. In the fourth quarter, net sales of FILSPARI grew by nearly 40% compared to the third quarter, and we saw a meaningful inflection in demand following full approval. This is a testament to our sound commercial execution alongside FILSPARI's strong profile with robust long-term efficacy, including preservation of kidney function and two year safety data. It also speaks to the ability for physicians to now prescribe FILSPARI to more of their patients with IgAN with a broader label and supportive draft KDIGO guidelines. I'm also excited about the progress we've been making in expanding FILSPARI's potential beyond IgAN. As we highlighted last week, we recently completed our Type C interactions with the FDA and plan to submit our sNDA for a potential FSGS indication around the end of this quarter. This submission, supported by compelling data from our DUPLEX and DUET studies that we believe are further validated by the findings from the PARASOL group could lead to the first-ever FDA-approved therapy for patients with FSGS by year-end. We continue to believe that FSGS represents an even greater potential opportunity to help patients, and we look forward to the submission and review process. In addition, we remain committed to generating further evidence to support FILSPARI's foundational positioning in IgAN and broad use, which Jula will touch on shortly. Also in the pipeline, we continue to believe in the disease-modifying potential for pegtibatinase and the hope it can bring to the HCU community. We are continuing to optimize our manufacturing scale-up of our pegtibatinase program, and I am pleased with our recent progress. Looking ahead into 2025, our strategic priorities are clear and focused. We will leverage our recent full approval and broader label to further solidify FILSPARI's foundational positioning in IgAN as the only non-immunosuppressive kidney-targeted therapy that has demonstrated superiority over historical standard of care. With a unique profile and unsurpassed clinical data, we believe that FILSPARI will be utilized as a new foundational therapy in IgAN now and into the future, replacing the traditional role that RAS inhibitors have played. We will also focus on submitting a high-quality sNDA for FSGS, working with the FDA throughout the review process, and preparing for a potential launch later this year. And lastly, with pegtibatinase, we aim to maintain the momentum in our CMC efforts to enable reopening enrollment in our Phase III HARMONY study, and we are on track to achieve that next year. Following our successful financing near the end of the year, we are well capitalized to execute on these key strategic priorities. Let me now turn the call over to Jula for the clinical update. Jula?

Thank you, Eric. I'd like to start with sharing some feedback from physicians following FILSPARI's full approval in IgA nephropathy. Nephrologists are expressing a greater urgency to get their patients with IgAN into complete proteinuria remission or less than 0.3 grams per gram. This is driven by the complete remission data from both PROTECT and SPARTAN studies that demonstrate that FILSPARI, particularly if used earlier, can get more patients into complete remission as well as the updated draft KDIGO guidelines that recommend earlier diagnosis and treatment to lower proteinuria targets. These data also show that patients reaching complete remission can achieve kidney function loss close to that of normal aging. Additionally, more physicians see FILSPARI as a foundational therapy. When we speak to nephrologists, foundational treatment is defined as non-immunosuppressive, kidney-targeted, and nephroprotective that can be used chronically in nearly all patients with IgAN. The foundational role of FILSPARI is supported by the fact that it targets directly two pathways causing kidney injury, is non-immunosuppressive and can be used safely long-term, and has efficacy based on superior kidney function preservation from a head-to-head comparison over a historical standard of care medicine, irbesartan. Also, with the removal of the 1.5 gram per gram threshold from the label following full approval in IgA nephropathy, we're hearing that nephrologists are seeking use in a broader eligible patient population. The new evidence presented at ASN Kidney Week demonstrating FILSPARI's efficacy in patients with lower proteinuria levels and the long-term safety profile continues to reinforce physician confidence in FILSPARI as a long-term treatment option for this larger segment of IgAN patients. Our medical teams are continuing with education on the data that supports FILSPARI's position as a foundational treatment for IgA nephropathy. This education focuses on the benefits of treating IgAN patients earlier and to lower proteinuria targets in line with the updated draft KDIGO guidelines. It also highlights evidence that supports earlier and broader use of FILSPARI as well as clinical studies on FILSPARI used in combination with other available medicines. For example, the Phase II SPARTAN study evaluates early use of FILSPARI as a foundational treatment with anti-inflammatory properties. Data from the study has shown a nearly 70% reduction in proteinuria and approximately 50% reduction in urinary inflammatory biomarker soluble CD163 over 24 weeks in newly diagnosed patients with IgA nephropathy. We expect additional data from this ongoing study later this year. I'm also excited to share that preparations are underway to expand the SPARTAN study to include post-kidney transplant patients with recurrent IgA nephropathy. We also plan to initiate a new open-label study of sparsentan to generate additional data with its use in post-kidney transplant patients with recurrent IgA nephropathy or FSGS. These patients are already on chronic immunosuppressive therapy to prevent organ rejection and remain at high risk of disease progression. There is clearly a significant need for a safe and effective non-immunosuppressive treatment option directly addressing the injury in the kidney, and we're looking forward to generating more data in this area of high unmet need. Turning to FSGS. We continue to believe that FILSPARI, if approved, could become a new treatment standard in this highly progressive disease. It is important to note that FSGS is heterogeneous. One of the distinct advantages we have seen in our development program is that FILSPARI has consistent efficacy data across disease subtypes, including in patients with genetic FSGS who are historically not responsive to treatment. This applicability is particularly important given the diverse patient population affected by FSGS and could uniquely position FILSPARI for broad use if approved. Importantly, our robust clinical data in FSGS is aligned with the findings from the PARASOL group and has demonstrated a clear correlation between proteinuria reduction and decreased risk of kidney failure. As we highlighted last week, we are very pleased with the progress on the regulatory front. Our recent interaction with the FDA provided clarity on our submission, and we are confident in the strength of our clinical data and believe it provides an opportunity for FILSPARI to potentially become the first approved therapy for patients with FSGS. As Eric mentioned, we plan to submit our sNDA around the end of the first quarter of 2025. Our medical teams are also preparing our physician education initiatives with an emphasis on the biologic plausibility of proteinuria as a causal marker of the disease and its impact on heart outcomes such as kidney failure. This will enable physicians to further understand the important role of proteinuria in FSGS. Turning briefly to our pegtibatinase program. As Eric mentioned earlier, we continue to believe in the potential for it to become the first and only disease-modifying therapy for patients with HCU. We are pleased with the progress on the optimization efforts for manufacturing scale-up and expect to restart enrollment in the pivotal HARMONY study next year. With that, I will now turn the call over to Peter for the commercial update. Peter?

Thank you, Jula. I'm pleased to share our exceptional commercial performance for FILSPARI during the fourth quarter, which marked our strongest period since launch. As expected, the conversion to full approval in the U.S. with an expanded FILSPARI label has accelerated our growth. In the fourth quarter, we received 693 new patient start forms, representing a 37% increase from the prior quarter, clear evidence of FILSPARI's growing adoption in the IgAN community. This growth has been driven by both new prescribers and increased depth among repeat prescribers. On the patient access front, we continue to have excellent coverage, and I'm particularly impressed with the advancements we have seen in payer formularies. This is best exemplified by updates of authorization criteria, reflecting the broader FILSPARI IgA nephropathy label, which will further ease access for patients with lower proteinuria levels. This will also be beneficial as we see more therapies come to market, which we expect will be mostly indicated for patients at high risk of disease progression or proteinuria levels of 1.5 gram per gram or above if under accelerated approval. In addition to the strong demand and access, we continue to see improvements in our fulfillment process as well as high compliance and persistence rates, all key fundamental drivers of a successful launch. These elements resulted in achieving approximately $50 million in net product sales of FILSPARI for the fourth quarter, nearly 40% growth over the previous quarter. To start 2025, we have been pleased with the continued strength in demand, and we are confident in FILSPARI's future uptake as we look ahead. For the foreseeable future, we expect FILSPARI will be the only foundational kidney-targeted non-immunosuppressive and long-term treatment option fully approved for IgA nephropathy. Furthermore, it is the only medicine that has demonstrated superiority versus an active control maximally dosed historical standard of care and has the flexibility to be combined with other modalities. This means that FILSPARI will be uniquely positioned as the only medicine of its kind indicated for all adult patients with IgA nephropathy at risk of disease progression. As the IgA nephropathy landscape continues to evolve and more therapies may get accelerated approval, we expect many of them to be complementary to FILSPARI and for them to have an initial label that will be limited to patients at high risk of progression, which has been defined as generally a proteinuria level of 1.5 gram per gram and above. While we are continuing to have success with FILSPARI in this high-risk segment, our estimates suggest this group of patients above 1.5 gram per gram is approximately 30% of the addressable patients with IgA nephropathy and is likely to diminish over time as more approved therapies may become available. We believe about 70% of the addressable patients with IgA have proteinuria levels between 0.3 and 1.5 gram per gram. Notably, this segment is expected to grow with earlier diagnosis, increased biopsies, and lower treatment thresholds target set by KDIGO. Consistent with our growth driver, the median starting proteinuria level for patients initiating FILSPARI is now below 1.5 gram per gram, which is a signal that we are making good headway in this population in the first few months following our full approval and that we have a good opportunity ahead of us. The updated draft KDIGO guidelines for IgA nephropathy are also expected to continue to be a large driver of change in physician behavior. This guidance encourages earlier diagnosis and treatment with more ambitious treatment targets of 0.5 gram per gram or preferably complete remission. As you heard from Jula, this will ultimately result in patients getting access to medicines earlier with the goal of achieving complete remission. The updated draft guidelines also highlight FILSPARI as the only kidney-targeted therapy that has shown superiority over an active control and maximally dosed RAS inhibitor, positioning FILSPARI as the only treatment option to replace the traditional role ADS and ARPS have historically played in IgA nephropathy. We expect this to continue to drive adoption among physicians and payers as the guidelines are finalized. Finally, the potential modification of the liver monitoring requirements, if approved this summer, could further ease the process of adoption and enhance the patient experience. Now let me briefly touch on the opportunity for FILSPARI in FSGS, if approved. As Jula outlined earlier, FSGS is the most progressive glomerular disease and is often manifested with extremely elevated proteinuria levels. The high and urgent unmet need of approved treatments for FSGS is well established across the nephrology community. Depending on label language and indication, we estimate up to 30,000 patients in the U.S. with FSGS could be addressable for FILSPARI if approved. Based on our assessments, we anticipate that over 80% of our target nephrologists are treating patients with IgA nephropathy and FSGS. With this high overlap of potential prescribers, the urgent need for medicines to lower proteinuria, and with FILSPARI's strong established position in IgA nephropathy, we are confident that we will see a strong uptake in FADS if approved. I'll now turn the call over to Chris for the financial update. Chris?

Thank you, Peter, and good afternoon, everyone. In the fourth quarter and entering the new year, our operations have continued to strengthen. As you heard from Peter, we have seen a meaningful inflection in net product sales of FILSPARI following full approval, and the outlook for the launch remains strong. We also continue to be measured in the investments we're making to drive our growth. I'll start with revenue, where we generated net product sales of $73.5 million in the fourth quarter, representing significant sequential and year-over-year growth. For the full year, net product sales were $226.7 million, a nearly 80% increase compared to 2023. FILSPARI continues to be the key growth driver, generating $49.6 million in net product sales during the fourth quarter and $132.2 million for the full year 2024, which outperformed benchmarks for the first full year of launch. Thiola and Thiola EC also contributed $23.9 million in net product sales for the fourth quarter and $94.5 million for the full year 2024. The slight decrease in Thiola's net product sales in the fourth quarter is a result of generic dynamics. Given there were several generics approved in 2024, for this smaller segment of our product sales, we do anticipate further headwinds throughout this year. During the quarter, we also recognized $1.2 million of license and collaboration revenue, which results in total revenue of $74.8 million reported for the fourth quarter and $233.2 million for the full year 2024. Turning to operating expenses. Our research and development expenses for the fourth quarter of 2024 were $62.1 million compared to $59.7 million for the same period in 2023. On a non-GAAP adjusted basis, R&D expenses were $58.6 million compared to $55.3 million for the same period in 2023.Selling, general and administrative expenses for the fourth quarter were $69.5 million compared to $63.6 million for the same period in 2023. On a non-GAAP adjusted basis, SG&A expenses were $51.6 million for the fourth quarter compared to $49.7 million for the same period in 2023. Overall, we reduced our R&D and SG&A expenses meaningfully in 2024.This was driven by the restructuring enacted at the end of 2023 as well as reduced clinical expenses as the FILSPARI Phase III studies advanced towards completion. This was partially offset by additional investment to support the commercial launch of FILSPARI in IgA nephropathy as well as pegtibatinase initiating its Phase III program and some early work to support a potential FSGS indication. Total other income net for the fourth quarter of 2024 was $0.4 million compared to $5.7 million in the same period in 2023. The difference is largely attributable to lower interest income during the period. Net loss, including discontinued operations for the fourth quarter of 2024 was $60.3 million or $0.73 per basic share compared to $90.2 million or $1.18 per basic share for the same period in 2023. Net loss, including discontinued operations for the full year 2024 was $321.5 million or $4.08 per basic share compared to $111.4 million or $1.50 per basic share for the same period in 2023. The full year 2023 includes a $265 million gain on sale that was recorded following the sale of our bile acid business. On a non-GAAP adjusted basis, net loss, including from discontinued operations for the fourth quarter of 2024 was $39 million or $0.47 per basic share compared to $71.8 million or $0.94 per basic share for the same period in 2023. The net loss for the full year in 2024 was $241 million or $3.05 per basic share compared to $20.6 million or $0.28 per basic share for the same period in 2023. As of December 31, 2024, we had cash, cash equivalents, and marketable securities totaling $370.7 million. This includes net proceeds of approximately $134.7 million from our successful financing completed in November. As we look ahead, we expect our business to strengthen further. From a revenue perspective, we expect a moderate increase in gross to net discounts compared to 2024, but we believe net product sales of FILSPARI and IgA nephropathy will grow significantly in 2025 and continue to outpace benchmark launches. We will also remain disciplined in our investments as we continue to support the successful launch in IgA nephropathy, prepare for a potential launch in FSGS, and further optimize our CMC efforts to restart enrollment in our pivotal pegtibatinase program. Additionally, we anticipate incoming milestone payments from CSL Vifor upon conversion of FILSPARI to full approval in Europe and achieving market access milestones later this year. With this plan, we project that our operating cash use will continue to decline over time and that our balance sheet will be able to support these investments aligned with the key priorities to advance our growth. I'll now turn it over to Eric for his closing comments. Eric?

Thank you, Chris. In closing, 2024 was a year of great execution and progress by all of our team members and partners. The bar is high, but we are positioned for another great year in 2025. Our team is starting the year focused on the three key priorities I outlined at the outset of our call. We believe these will deliver value for patients and all of our stakeholders in the near and long term. And we will look forward to keeping you informed as we reach key milestones throughout the year. Now let me turn the call over to Victoria for Q&A. Victoria?

Thank you, Eric. Cloy, we can now open the line up for the Q&A.

Thank you. Ladies and gentlemen, we will now begin the question-and-answer session. [Operator Instructions] We will now take the first question from Malcolm Rama from JPMorgan. Your line is open.

Hi. This is Malcolm Kuno on for Anupam Rama. With the expanded FILSPARI label, what are you seeing in terms of patient uptake?

Thanks, Malcolm, for the question. I will turn that one over to Peter.

Yes. I think the most important aspect is what I called out in the prepared remarks is that we saw a meaningful increase in new patient start forms with 37%. But we also see that we have more use now in patients with lower proteinuria levels. And I think that makes sense given that our accelerated approval was really focused on patients at risk of rapid progression, generally a proteinuria level of 1.5 grams per grams or higher. And in the full approval, you have no longer like a proteinuria threshold. And we start to see that being reflected also in the patients that are being prescribed FILSPARI.

Yes. Thank you, Peter. Malcolm, the only other thing that I would add is that we've seen a continued increase in the number of new prescribers, particularly those that were waiting for full approval in that broader label. And so I think as Peter has discussed this in prior calls, it gives us great confidence that with that clinical experience, we're going to continue to see uptake as they find new patients.

Okay. Thank you.

Our next question comes from the line of Vamil Divan from Guggenheim. Your line is open.

Great. Thanks for taking my question and congrats on the progress. So just one, and you touched on this a little bit in the prepared remarks, but just obviously, you might get a new competitor entering the IgAN space from Novartis. I'm just curious maybe you can provide a little more just thoughts on how that might impact FILSPARI's uptake, how you sort of see the competitive dynamics evolving here over the next several quarters, especially if the liver safety monitoring, if there's a difference between that label and your label. Thank you.

Vamil, thanks for the question. We remain very confident in the profile and the outlook for growth of FILSPARI. And I'll hand it over to Peter to provide a little bit more comments on our assessment.

Yes. Thanks for that question. I believe you mentioned Novartis as a potential new competitor. Well, there's actually two. Fabhalta was launched last year in the fall and Q4 was the first quarter that we have Fabhalta entered the marketplace as well. Despite that, we saw that to be our strongest quarter till date. So we haven't seen much competition there. But it also makes sense because it's a different mode of action, and it's a different treatment category. I think what you may be alluding to is the potential approval of atrasentan that would play more in the same treatment category. And a couple of things I would want to say on that. Let me start with saying that it's good to have another company that is talking about the importance of endothelin as a bad actor in disease progression, in particular regarding kidney injury. When I look more specifically within the treatment category of foundational treatment, I'm confident in the strong and differentiated FILSPARI profile, both in efficacy as well as in convenience. The reason why is FILSPARI is simultaneously blocking angiotensin as well as endothelin. That consistent inhibition resulted in the impressive 50% reduction in proteinuria that we saw after nine months that largely sustained over the two year period in PROTECT, resulting in an improvement of kidney preservation year-over-year. We can talk about that full benefit of FILSPARI and how it translates into long-term benefits. A new entrant will not be able to do that. They will be segmented to like the nine month proteinuria label as well as what I mentioned before, likely an initial label will be focused on the more rapidly progressive patients with proteinuria of 1.5 grams or higher. So I think we have a very strong profile. I would also say FILSPARI offers flexibility in dosing with the 200 and the 400 milligrams that I don't think atrasentan will be providing. So all in all, I feel very strongly where we are positioned. And yes, more to come on this one once they may be approved for IgA nephropathy.

Yes. Thank you, Peter. And Vamil, just to close out on the last part of your question with regard to REMS. I think we need to see what their label if and when approved, what that looks like. But regardless, for all of the reasons that Peter said, we believe that we have a very competitive profile and we'll be prepared for any scenario.

Okay. Thanks for the questions.

Thanks, Vamil.

Our next question comes from the line of Laura Chico from Wedbush Securities. Your line is open.

Hey, guys. Thanks very much for taking the questions. This is Dylan on for Laura Chico. So realizing the FSGS launch will change the trajectory of overall FILSPARI revenue, when might you be in a position to provide guidance for the IgAN setting?

Yes, Dylan, thanks for the question. So we've been very pleased with the uptake, particularly since full approval in Q4. With that said, it's really just one quarter, and we're pleased to see how the first quarter is starting. But we do want to make sure that we have a bit more data points to be able to estimate that. So it's something that we consistently are looking at, and we'll provide further updates along the way. But at this point, we're not in a position to provide guidance, but certainly are looking at that.

Thank you.

Thank you.

Our next question comes from the line of Maury Raycroft from Jefferies. Your line is open.

Hi. This is Farzin on for Maury. I wanted to ask on the BD side. Like you have noted continued BD to diversify the pipeline. So what should we expect this year? Like will you be looking to potentially in-license assets in the rare renal space? Or will it be more focused on the FSGS launch?

Yes. Thank you, Farzin. And I would say that our teams certainly are looking. It's an exciting time. I've talked about this area really as a renaissance within the rare renal space. And we believe that with the capabilities, the experience, and the infrastructure that we certainly could add value to other potential medicines that are in development. So something we're looking at, always hard to be able to provide specifics on timing, but certainly, it's aligned with our strategy. With that said, our #1 priority is to make sure that we are able to bring FILSPARI to patients with FSGS. And so our preparation for the launch will remain our top priority while in parallel looking at opportunities to diversify and bring potential therapies to patients that don't have any.

Okay. Thank you.

Thanks, Farzin.

Our next question comes from the line of Tyler Van Buren from TD Cowen. Your line is open.

Hi. This is Greg on for Tyler. Thanks for taking my question. So assuming the FILSPARI REMS modification will be approved at or around the PDUFA date, what steps remain towards the ultimate goal for full removal of the REMS? And is there a precedent for this happening?

Sure. Thanks for the question, Greg, and I'll turn that one over to Bill.

Thanks. Yes, the first step, as you noted, we'll learn our outcome this summer, the end of August with our major REMS modification request where we're looking to change from monthly to quarterly monitoring in the first year. The agency had specified when we discussed this in the past and from a post-marketing perspective, they wanted to see a certain amount of exposure, about 3,000 patients over two years in order to have enough data to entertain the discussion around full removal of the REMS. We're not at that point, but we're well on our way and look forward to that in the future. But as I said, the first step is changing the frequency from monthly to quarterly upon initiation.

Great. Thanks again and congrats on another successful quarter.

Thank you, Greg.

Our next question comes from the line of Joseph Schwartz from Leerink Partners. Your line is open.

Thank so much. Based on reported sales and the current price, it looks like there might be around 2,000 patients on FILSPARI at the end of the year. And I think the company has received over 3,600 PSFs since the beginning of the launch. So I was wondering if you can provide us with any additional context on the conversion of PSFs to patients on therapy as well as the discontinuation rate. Can you help us envision what the difference between these figures is accounted by?

Joe, thanks for the questions, and I'll turn that one over to Peter.

Thank you, Joe, for that question. It's a good question. I think overall, I would say that we have a very strong fulfillment right now. If you look at our growth trajectory in patient start form, it equals quite nicely what we see in revenue as well. And I think that speaks to the improvements we have made in our fulfillment. Last year, about 1 year ago or 1.5 years ago, we also commented like early on in the launch, there was a pocket of patients that required a little more handholding in the REM certification process, in particular, as in the first 60 days, we weren't able to promote FILSPARI and basically only had the label or the package insert. Now that we have overcome that and especially now with the full approval where you have the full data package, both from an efficacy as well as safety package to have that conversation with patients and make them more comfortable about the treatment option for FILSPARI, we have seen really strong improvements in our fulfillment process. Having said that, you also have to realize you never get to 100% conversion of all patient start forms. I mean even in retail, and we have done some research on that, even in retail nephrology products, you have about 85% to 90% of the patients that are picking up their medicine. The rest never pick up their medicine. So there is a certain leakage points. I think we have identified where those leakage points are and were, and we have made good progress on that. So I will expect that you will see continuation of stronger transition of patient start forms to paid performance.

Yes. Thanks, Peter, for that. And Joe, the only thing I would add just as another data point for your question around discontinuation rates, we continue to see very high compliance and persistence rates. So this is not a medicine where you see a disproportionate number of patients that discontinue once they start. So really, the focus, as Peter talked about, is having the teams get the patient from patient start form on the therapy. We've seen really good progress, as Peter talked about. Once the patient is on, there is such a consistent positive experience, including as we saw our label expand, we've been very pleased with that part of the launch.

Thanks for the color.

Thank you.

Our next question comes from the line of Liisa Bayko from Evercore. Your line is open.

Hi there. Thanks for taking the question and congratulations on all the progress. I have a couple of questions actually. First of all, can you just give us a sense of gross to net and how you're thinking about it for this year?

Sure. Chris, why don't you take that one?

Sure. So Liisa, as you might remember, we had previously guided for last year for FILSPARI to have gross to net to be in the mid to high teens with the highest part of that occurring in the first quarter and then evening out through the balance of the year. This year, we're expecting it to be a bit higher. And so I think the best way of thinking about that is probably high teens to low 20s. And it's going to be a similar phenomenon where we expect the greatest impact early in the year and for it to be a little bit more even through the balance of the year. So hopefully, that helps.

Okay. Great. And how is it going in the beginning of the year with kind of having -- do you have to -- are the patients required to renew any prior authorizations or anything like that? Should we expect any bumpiness in the first quarter for that reason?

Yes. Great question. Peter, why don't you take that one?

Yes, we haven't really seen that to be an issue. I mean the -- you're right. You have the renewals of payer plans, in particular in the beginning of the year, but we haven't really seen an impact on that so far. I would say what I mentioned in the prepared remarks, I'm in particular very pleased with how payers are already adopting the broader label for FILSPARI, some of them completely removing proteinuria levels, and step edits. So I think we made really good progress. But to your specific question on renewal criteria, we haven't really seen an impact there.

Okay. Great. And then finally, I wanted to ask about sort of more about the future, and we can even go beyond the initial rollout of some of the new forthcoming APRIL and APRIL BAFF compounds. But when they do get a full label and we're kind of in that era, how are you thinking about the potential use of two branded medicines? Is that something that you think is going to be widely accepted because ideally, you'd want to be on combination of FILSPARI or some of these newer mechanisms? Or do you think you'll have to step through one to the other? Or will there be some other criteria? Will you have to pick and choose between these? I'm just curious how you're thinking about it and if you've gotten any feedback on that point from payers specifically. I know physicians want to use all the best drugs. So that's less of a concern and kind of really focused more on the payers.

Yes. It's a really good question, Lisa. And this is one that we've been very consistent over the years that we've been predicting that this is going to be the future of IgAN treatment. And that's largely why we have generated data on combinations. We're eager to see the ability to be able to look at combinations in newer immunosuppressants. With that said, I'll turn that over to Peter to get comments on what we're seeing to date in the market as well as feedback from payers.

Yes. Thanks, Lisa. It is a really good question. And I think there will definitely be excitement across the nephrology community to combine different treatment modalities, in particular, when it's different treatment categories. And if you read the KDIGO guidelines, that's something that they're advertising as well. So it's really about the payer, to your point, like what is the payer accepting with regards to combination. In that regard, I am, in particular, very confident with our formularies and payer inclusions already, also given that we really have the gold standard of how payers evaluate medicine. Payers generally want to see direct head-to-head maximally dosed comparison studies, and that's exactly what we have. On top of that, FILSPARI is priced for broad access. I was talking about the broad patient population that FILSPARI is applicable to. We have priced accordingly. So it's up to the new entrants, how they price that, and what evidence they will bring to the table to see how they may be combined with FILSPARI. But I'm very pleased and very confident with our payer inclusion criteria so far. And to Eric's point, we have been planning for this.

Thank you.

Thank you.

Our next question comes from the line of Yigal Nochomovitz from Citigroup. Your line is open.

Hi. Thank you. Just a couple of things. So on the REMS, if you do get the shift to the quarterly, is it the expectation that that would flow to the label on FSGS or that's a different conversation? If you could answer that, please.

Yes, I can answer that. So we would assume that FSGS will have the same labeling and same REMS if and when approved. So whatever happens at the time of approval would carry through.

Okay. And then assuming it does go to quarterly, at that point, the next step on the pathway would be to nothing? Or could it be like annually? How do you foresee that thinking going forward?

Yes. Our plan has always been two-step process, one, to modify and second, to remove. So assuming we are able to get that to quarterly, the next step would be removal of the REMS.

Okay. And then you may have answered this one in the past, but on pricing, given the dosing increase with FSGS, is it fair to assume it's simply going to flow to be twice the price? Or is there going to be some economies of scale there that are incorporated in the pricing discussion on FSGS? Thanks.

Yes. So I mean, first of all, our pricing strategy is really to ensure broad access because like IgA nephropathy, we are assuming that the broad community of FSGS patients could benefit from FILSPARI if approved. So it's certainly something we'll look at. It's premature for us to talk in specifics, but I will have Peter talk a little bit about what the dynamics are that are different in FSGS, including dosing.

I think generally, I mean, the value proposition is probably different in FSGS as well because it's a different patient population. And as I mentioned in my prepared remarks, this is the most progressive glomerular disease and patients with the highest unmet need. So the value proposition is higher here as well. But to the point, we have doubled the dose, and with linear pricing that may potentially end up to double the price as well. We're really focusing on what the value proposition is. This is something we don't start from scratch. I mean we were initially planning for FSGS as our first indication. So a lot of the work has been done already. But now we are refreshing it and rebuilding the value proposition for potential FSGS launch.

Got you. Thank you very much.

Thanks, Yigal.

[Operator Instructions] Our next question comes from the line of Prakhar Agrawal from Cantor. Your line is open.

Hi. Thank you so much for taking my questions. So there are a lot of competitive readouts in the IgAN space coming over the next one to two years. Can you give your perspective on how long will the accelerated approval path in IgAN will remain open since two drugs have full approval now? And what will the competitors need to show to get accelerated approval? Thank you.

Yes. It's a really good question, probably one that you might not be satisfied with our answer because it's very difficult for us to predict. With that said, Bill, I'll turn it over to you for any potential thoughts.

Yes. I appreciate the lead-in, Eric, because it's us speaking for the FDA, which isn't where we can speak with authority. But at some point, the agency will make the judgment that the unmet need in IgA nephropathy and for that patient population has been met sufficiently to the point where accelerated approval is no longer a viable pathway. I do know that Dr. Aliza Thompson has said at the podium publicly, this is not a pathway that will stay open indefinitely for IgA nephropathy. So at some point, they are going to make that distinction. We have three drugs approved that have certainly increased in the armamentarium that physicians have to treat this disease. I think certainly, you've got some of the BAFF APRIL B-cell initiatives that are on an accelerated approval pathway, but I don't expect that too many of those will be able to get there. And like you, we're watching to see when that change occurs.

Thank you.

Thank you, Prakhar.

Our next question comes from the line of Mohit Bansal from Wells Fargo. Your line is open.

Hi. This is Fadi Ahman on for Mohit. Thanks for taking our questions. So on the point about the expanding prescriber base after the full approval in IgAN, can you give some sense of the number of IgAN patients on average that these new prescribers treat? I know this is a highly fragmented market. So I imagine you've targeted the high prescribers earlier in the launch. So just trying to understand if there's potentially a lot of depth to the new prescribers that are coming on now. Thanks.

Sure. Thank you. I'll turn that one over to Peter.

Yes. As we have mentioned in the past, we target about 6,000 nephrologists out of, I would say, a U.S. universe of about 10,000 that 6,000 nephrologists approximately treat 85% of the IgA nephropathy patients in our estimations. To your other point, so you have to go quite broad to cover and get access to all the patients. I would say, in general, many of those nephrologists see five to 10 IgA nephropathy patients in their practice, but it depends on -- you have like higher volume offices as well. And yes, we are targeting those offices more heavily. But overall, you have to cast a broad net across both academia as well as the community of nephrologists.

Yes. Thank you, Peter, for that. One thing that I would add is unlike many other rare diseases, you don't see the type of referral patterns -- and therefore, you don't see as much concentration of patients being treated within a small number of centers. There's quite a breadth, which I think really explains why Peter's team is going quite broad within the nephrology community, quite different from other rare diseases. And I think if we take a step back, what that signal should signal is that we have a substantial opportunity to continue to grow by reaching many more of these patients in the years to come.

Got it. Thank you.

Thank you.

Our next question comes from the line of Greg Harrison from Scotiabank. Your line is open.

Good afternoon. Thanks for taking the questions. Could you speak to the potential impact commercially from a REMS modification as far as any patients who maybe can't comply with the liver monitoring currently and thus aren't receiving FILSPARI, and may initiate treatment after the REMS potentially becomes less onerous?

Great. Thanks for the question, and I'll turn that one over to Peter.

Yes. Thanks, Greg. It's a good question. I would say, I mean, REMS has not been an obstacle for FILSPARI so far, especially if you compare the FILSPARI performance relative to recent benchmarks, I think we outperformed those benchmarks even though they didn't have REMS and we have REMS. To your question, what is the additional upside if you have an easing or a modification of the REMS, what would it do? I would say the main impact that I'm expecting is that physicians are broadening their perspective of what patients could be eligible for FILSPARI and what patients will be compliant to monthly monitoring as well. That's the only thing that I sometimes hear from physicians that they have quite a preconceived notion like what patients would be compliant with that monthly monitoring. If you go to three monthly from the very beginning, that would broaden the patient selection for physicians, and that's why I really see the opportunity.

That’s helpful. Thank you.

Thanks, Greg.

Our next question comes from the line of Jason

Good afternoon. Congrats on the progress and thank you so much for taking our question. I was hoping you could provide some additional color regarding your prelaunch activities in FSGS. I know, Jula, you mentioned expanding awareness of proteinuria as a biomarker. But based on PSL, there seem to be pretty broad support, at least maybe from the academic providers. Curious if you see this as a bottleneck in the more broader community. And I don't know, any other potential headwinds or, I guess, opportunities to maybe smooth adoption out?

Sure. Thanks for the question, Jason. I'll first hand it over to Jula to talk about what her team will be doing. And then, Peter, you can talk about what your team will be preparing for.

Yes. Thanks for that question. I think it is really important to continue to reiterate not just with academicians, but across the spectrum with private practitioners that proteinuria is in the biologic pathway for progression to kidney failure. And we know that. That's how we treat our patients. But just to reiterate that eGFR is noisy and over the short term, it can be challenging to show a treatment effect even if you might see a good relationship over the long term. And so it really is reinforcing that if you can reduce proteinuria, similar to what we saw in both DUET and in DUPLEX and consistent with PARASOL that you can reduce the rate of loss of kidney function and minimize rates of kidney failure. That's a key aspect of what we're educating around and what we need to continue to reinforce as well as education around our data. And I'll turn it over to Peter for continued discussion.

Thank you, Jula, and thank you, Jason, for that question. As I mentioned earlier, FSGS treaters are largely the same prescriber base as FILSPARI. There's like an over 80% overlap in those physicians that we are targeting today. So there is a high familiarity and brand awareness for FILSPARI already among those physicians. And many already have the experience with FILSPARI as well. I think most importantly is that we are building upon our established organization, allowing for a rapid uptake in FSGS while also continuing our growth trajectory in IgA nephropathy. I talked to you about the physicians already. I think we are well covered there and the best pre-marketing for FSGS is really getting experience with FILSPARI and IgA nephropathy. From a patient perspective, we recognize that there are different patient communities. And so we are really focused on like what is the patient journey and what can we learn with regards to intervention points. And that is the work that we are assessing right now. And then the third aspect is really the payer and the health economic assessment that I was talking about earlier, really building out that value story for FSGS. As I mentioned earlier, a lot of this work has already been started as we were planning for FSGS as the initial indication originally. But I think in summary, we will be well prepared at the time of approval for FSGS by the end of the year.

Got it. Appreciate the deep color, guys. Thanks.

Thank you, Jason.

Our next question comes from the line of Alex Thompson from Stifel. Your line is open.

Hey, great. Congrats on the update. I guess on shifting gears to pegtibatinase. Could you talk a little bit more on sort of the progress that you've made on restarting the Phase III and when we might learn more about the timelines there? Thanks.

Certainly. Thank you. I appreciate the question on pegtibatinase. Bill, I'll hand that one over to you.

Certainly. As you're aware, we work with CDMO partners externally on the manufacture of the recombinant enzyme. And the scale-up challenges that we have observed are ones that our partners have seen before and have worked through before. And with that, the path has been pretty clear. We're pleased with the progress on the necessary process improvements that we're seeing in the manufacturing scale up to date. And we expect to restart enrollment in HARMONY in 2026. I don't have a specific point in the calendar to point to where we'll have more specificity that's really going to be data-driven and how the experimental data comes from those efforts on scale-up.

Do we have any another questions?

Our next question comes from the line of Ed Arce from H.C. Wainwright. Your line is open.

Great. Thanks for taking my questions and congrats on another strong quarter of progress here. So try to get three in here quickly. First, with regard to FSGS, obviously, this pathway now has rather quickly presented itself based on the findings from PARASOL. And so the first question is, if it comes to pass that there is an ADCOM, what kind of specific questions would you expect the panel to sort of challenge the findings from PARASOL on given that that's the basis? And then secondly, I know we've talked about this a little bit on the call, but I'm just wondering regarding pre-commercial activities for FSGS Obviously, this would be the first approved drug, and you've talked about the 80% overlap in patients. So some strong structural components to the launch itself. But just wondering what specific activities would you be focused on to really ensure rapid uptake right from the start. And then lastly, given that overlap between the two indications, wondering how much additional SG&A investment you would be considering around the end of the year, if that's when the launch happens? Thanks so much.

Okay. Thanks so much for the questions, Ed. I'm going to take them in the opposite order, and then I'll leave the ADCOM question for Jula Inrig. The SG&A will be incremental. We have the infrastructure. And so a lot of the readiness is there. There will be some variable spend, but that's largely going to occur once we are and if we are approved. With regard to pre-commercial activities, it's a lot about planning. We do not promote pre-approval. So it's really about preparing and understanding the journey of the patient and the needs of the physicians, as Peter outlined. But we've got a team in place. They're in the field. They've got a job, and that is to identify and treat additional patients with IgAN. And as Peter said, that's really going to help in establishing that trust, the relationships, and the profile of FILSPARI. So that really is largely the activities. And I think one thing we've mentioned in the past, but I think it really bears repeating on this question is nephrologists know that there is an urgency to treat patients with FSGS. It's very different than how they were trained on IgAN. There is a desperation for something to be approved in FSGS. So I think that that's a dynamic that is going to play out if we are approved. And with that, I'll turn that over to the question about the ADCOM questions to Jula.

Well, thanks for the question, Ed. I think a big part of an ADCOM is education as well as helping the agency to understand the overall benefit risk of any potential new therapy. So some of the key questions that will be asked is similar to what's already been done within PARASOL is what is the clinical meaningfulness of the magnitude of proteinuria reduction that was seen with sparsentan? And what does that translate into? And realize that when you have an ADCOM, it's not just for the nephrology community and the FDA, it's also for other stakeholders who have patients there. So it gives the agency and us an opportunity to discuss all of the evidence and data and hear back from key stakeholders, including patients.

Great. Thanks so much.

Thanks, Ed.

Ladies and gentlemen, this concludes the question-and-answer session of today's conference call. I'll hand the call back over to Victoria.

Thank you, Cloy, and thank you, everyone, for joining our Fourth Quarter and Full-Year 2024 Financial Results Call. We look forward to seeing everyone at the upcoming spring conferences. Have a great rest of your day.