TVTX - NASDAQ

Good day, and welcome to the Travere Therapeutics Second Quarter 2023 Financial Results and Corporate Update Conference Call. Today's conference call is being recorded. At this time, I would like to turn the conference call over to the Vice President of Investor Relations, Naomi Eichenbaum. Please go ahead, Naomi.

Thank you. Good afternoon, and welcome to Travere Therapeutics second quarter 2023 financial results and corporate update call. Thank you all for joining us. Today's call will be led by our Chief Executive Officer, Dr. Eric Dube. Eric will be joined in the prepared remarks by Dr. Jula Inrig, our Chief Medical Officer; Peter Heerma, our Chief Commercial Officer; and Chris Cline, our Chief Financial Officer; Dr. Bill Rote, Senior Vice President of Research and Development will join us for the Q&A session. 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 statements. 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 Form 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 August 3, 2023 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. Eric?

Thank you, Naomi, and good afternoon everyone. In the first half of 2023, we made significant progress on our corporate strategy of delivering new treatment standards from our pipeline of innovative medicines for people living with rare disease. Our progress has been led by the ongoing successful launch of FILSPARI or sparsentan. FILSPARI is the first and only nonimmunosuppressive therapy approved for the reduction of proteinuria in adults with IgA nephropathy or IgAN at risk of rapid disease progression. We believe that FILSPARI holds the potential to help 30,000 to 50,000 addressable IgAN patients and our field teams continue to hear from nephrologists that their experience with FILSPARI is reflective of an efficacy and safety profile demonstrated in the interim readout from the PROTECT study. In fact, last week, I spent a day in the field with a FILSPARI sales representative visiting community nephrologists. One physician shared a compelling patient story about a young woman with IgAN at risk of rapid disease progression and struggling with proteinuria levels above two grams per day despite treatment with several therapies. After a few short weeks until on FILSPARI, the proteinuria level has significantly dropped below one gram per day. The physician noted that these types of results provide them with confidence to prescribe FILSPARI to a greater number of their addressable patients with IgAN. We are encouraged to hear this positive feedback from the field and the nephrologists are both represcribing and proactively identifying more eligible patients to use FILSPARI in their practices. These insights on physician feedback and demand provide us with confidence in the potential of FILSPARI to ultimately become a new treatment standard for IgAN. In the second quarter of 2023, we executed on our FILSPARI launch strategy and are observing strong performance on the two most important indicators of success, demand reflected in the growth of patient start forms or PSFs and patient access, driven by increasing and broader payer coverage. In fact, we delivered the highest number of PSFs in the first quarter launch since launch amongst other rare renal launch benchmarks. Later this year, we expect to announce the complete results from the PROTECT study that we believe will have the potential to support traditional approval and the potential for a broader label of FILSPARI in IgAN. The study is ahead of our initial guidance and we now expect a top line readout from PROTECT late in the third quarter or early in the fourth quarter. Looking beyond the US, we continue to work with our collaborator CSL Vifor. Regulatory reviews in Europe are underway for sparsentan in IgAN and we anticipate an opinion from the CHMP around the end of this year. Our top priority is ensuring a successful launch of FILSPARI and we believe that we are off to a strong start. In parallel, we have also continued to make progress on our other pipeline programs. We continue to believe that sparsentan may represent an important treatment option for patients with FSGS. In May, we reported top line results from the Phase three DUPLEX study of sparsentan in FSGS, in which sparsentan demonstrated significant and durable effects of proteinuria reduction, positive trends on eGFR and a well-tolerated safety profile over two years of treatment. While the study did not achieve statistical significance on the eGFR endpoints, we are encouraged by the totality of data. We are scheduled to meet with the FDA to explore the potential for a future regulatory submission for sparsentan in FSGS and expect to provide an update on that discussion in the fall. Shifting to pegtibatinase. With the recent positive update from Cohort 6, we are even more confident that pegtibatinase represents a significant opportunity for us to help patients with HCU and for our company to accelerate our growth in the coming years. Based on our growing body of market research, we understand there to be a population of approximately 3,500 addressable HCU patients in the US, a similar number in Europe and a meaningful number of patients in additional geographies. Importantly, over time, we see this addressable patient population potentially increased by 50% or more with the introduction of an innovative new therapy and advancements in diagnostics. This is why we are excited to continue focusing our efforts on this program and we are working towards initiating the pivotal study by year-end. Outside of our innovative pipeline, we recently announced that we have entered into an agreement for the sale of our bile acid product portfolio for up to $445 million, consisting of $210 million upfront and up to an additional $235 million in potential future sales-based milestone payments. This divestment, which is expected to close during the third quarter will meaningfully strengthen our balance sheet and most importantly has clear strategic benefits for our organization. Strategically, it will enable us to focus even more clearly on the successful launch of FILSPARI and IgAN, pursuing a potential regulatory path for sparsentan in FSGS, the development of pegtibatinase for the treatment of HCU. We believe successfully developing -- delivering on these priorities will position our medicines to become potential treatment standards each in markets with billion-dollar potential. Overall for the second quarter I am incredibly proud of our team's performance. We continue to progress each of our strategic priorities and have made important advancements with our pipeline of innovative products. We have successfully delivered a strong first full quarter of the launch, laying the groundwork for our goal of enabling FILSPARI to ultimately become the foundational therapy in IgAN. Let me now turn the call over to Jula for a clinical update. Jula?

Thank you, Eric, and good afternoon, everyone. I'd like to start by reflecting on the exciting development for FILSPARI in the first half of 2023 and touch upon the important updates to come later this year. While there have been meaningful developments in nephrology over the last decade IgAN remains one of the greatest unmet needs in rare kidney disease. IgAN patients are often uncontrolled and on average progress to kidney failure within approximately 11 years. Therefore, IgAN was a major focus at the recent European Renal Association or ERA Medical Congress where the Travere team showcased significant advancements in the field of rare kidney disease with nine posters and presentations. The analyses from the UK National Registry of Rare Renal Diseases or RaDaR demonstrated that most IgAN patients will face kidney failure within their lifetime, typically occurring in a patient's late 40s. Importantly, the RaDaR study confirmed the relationship between reductions in proteinuria at nine months, which is aligned to our 36-week PROTECT study interim analysis proteinuria time point and subsequent preservation of kidney function. The landmark analysis from RaDaR showed that a 50% reduction in proteinuria at nine months reduced the rate of eGFR decline and delayed time to kidney failure or death by 8.5 years. These results highlight that patients with IgAN need both early and effective treatment options capable of significant, chronic reduction of proteinuria to preserve kidney function. Currently there is only one approved nonimmunosuppressive therapy that has demonstrated such a rapid and sustained proteinuria reduction and early positive trends on kidney failure outcomes and that is FILSPARI. At the interim analysis of the PROTECT study, which supported FILSPARI's accelerated approval, we observed a 50% reduction of proteinuria from baseline compared to 15% with maximally titrated irbesartan. Additional data showed that greater proportions of patients on irbesartan as compared to FILSPARI reached a 40% decline in eGFR from baseline kidney failure or death. Furthermore new data from interim assessment of the PROTECT study presented at ERA show that a significantly greater proportion of patients on FILSPARI achieved complete and partial remission of proteinuria, which continued to accrue over the study period, demonstrating the rapid and durable effectiveness of FILSPARI. We head into the upcoming two-year top line readout from PROTECT with confidence. Based on the magnitude of proteinuria reduction observed with sparsentan as compared to irbesartan and encouraging trends on kidney outcomes at the interim assessment in PROTECT, we believe the trial is well-powered to show a clinically meaningful and statistically significant treatment difference on eGFR at two years. This is well-supported by the robust clinical literature from precedent studies demonstrating the relationship between proteinuria reduction and long-term eGFR benefit in IgAN. Furthermore, as part of our NDA review, we provided the FDA with conditional power calculations based on trial level analyses and the available interim eGFR data. These eGFR trend analyses supported the accelerated approval of FILSPARI for patients with IgAN and further support our expectation of a statistically significant two-year benefit on eGFR. We remain very pleased with the ongoing conduct of the PROTECT study. As Eric highlighted, we are now scheduled for our top line readout in the late third quarter or early fourth quarter of this year. These data are expected to support the submission for traditional approval, which we anticipate should include a label expansion to reflect the broader population and long-term benefits of FILSPARI, positioning it to become the foundational therapy in IgAN. Moving to FSGS. Since we reported the results from the DUPLEX study, our team has been actively engaging with rare kidney disease experts, practicing nephrologists and patient advocacy organizations. The overarching theme of these discussions is the high unmet need, the difficulty in studying a heterogeneous disease such as FSGS and strong support for the scientific rationale of sparsentan in FSGS. This broad encouragement combined with the positive trends seen in the ongoing analysis of the DUPLEX data support our justification to seek a path forward with regulators. A meeting with the FDA is scheduled and we expect to be in a position to provide an update from the meeting in the fall. We also are planning on presenting a more comprehensive analysis of the DUPLEX study data at a scientific meeting later this year. Moving beyond sparsentan, I'll briefly touch upon the advancement of pegtibatinase for the treatment of classical homocystinuria or HCU. In late May, we provided positive top line results from cohort six of the Phase 1/2 COMPOSE study. Specifically, treatment with pegtibatinase resulted in a consistent benefit across the patient population with a mean reduction in total homocysteine of 67.1% and achieved total homocysteine levels that according to physicians could support diet liberalization. This is very important for patients that are typically on a highly restrictive low-protein diet. There have been no significant safety concerns reported to date with pegtibatinase. Mild injection site-related reactions were observed and managed with conservative treatment. With this emerging clinical profile, we believe that pegtibatinase can effectively replace the deficient CBS enzyme activity addressing the high unmet need in HCU and can ultimately become the first disease-modifying therapy for patients. Engagements with regulators are progressing well. We currently have alignment on the use of total homocysteine as the primary endpoint for the Phase 3 study and the focus of our ongoing regulatory engagement is to align on finalizing details of the Phase 3 program now with the Cohort 6 data in hand. We look forward to providing an update on the details of the Phase 3 study later this fall with the expectation of initiating a pivotal study by year-end. With that I'll turn it over to Peter for the commercial update. Peter?

Thank you, Jula, and good afternoon, everyone. Our ambition is to make FILSPARI a new treatment standard for igAN patients at risk of rapid disease progression. And I'm really pleased how we have started in the first 4.5 months since launch to realize this ambition. We have made significant progress on our three strategic fundamentals that I outlined on the approval call in February. First, changing the treatment paradigm by educating physicians about FILSPARI's novel mode of action and unprecedented efficacy and safety profile; second enabling broad access for eligible patients to increasing payer coverage; and third, ensuring a positive initial experience with FILSPARI for patients and nephrologists. Let me provide you with some further call on our three areas of focus for successful launch. Starting with physicians. In for launch our dedicated field force has been able to engage with 4,500 nephrologists in face-to-face interactions. These engagements are having the intended impact. Nephrologists are increasingly understanding FILSPARI's novel mechanism of action that provides rapid and sustained proteinuria reduction in IgAN patients including those at risk of rapid disease progression. We also see continuing increase in awareness of FILSPARI. Based on market research findings, the aided awareness is already at nearly 90% of those surveys and over two-thirds of the nephrologists know about FILSPARI without prompting. More importantly, 50% of these nephrologists report seeing FILSPARI as a substantial advance over other therapies and the intent to treat within the first year of approval remains high at 90%. Now our field force can start using branded campaign materials consistent with FDA guidance for accelerate approved products, while also launching speaker programs we expect to further strengthen the awareness of FILSPARI. This positive momentum is also translating into behavioral changes as demonstrated by increasing demand. This has resulted in 417 new patient platforms in the second quarter. And in the first 4.5 months since approval, we have received a total of 563 patient start forms. As we have highlighted, since approval we view these patients start forms as the fundamental indicator for treatment demands. And it is the key metric contributing to our confidence in the successful launch. To put this into perspective, the new 417 patient start forms were received in our first full quarter. When comparing these to other recent rare nephrology launches the demand for FILSPARI outperformed these benchmarks within the same period. Additionally, we continue to observe an increase in number of prescribers and repeat prescriptions by the same nephrologists, indicating that they are seeing the potential treatment benefit for their addressable IgAN patients and starting to change their treatment paradigm with FILSPARI. Let me now shift to the progress that we have been making on the payer access front. We are very pleased with the engagement we continue to have with payers and how they perceive the value that FILSPARI is bringing to patients. The investment we made early on in generating the health economic evidence and developing the FILSPARI value story has been important in helping payers understand the utility of FILSPARI. We ended the second quarter with 54% of US lives covered in payer policies with about 50 formularies that have FILSPARI-specific policies. And we are really pleased with the quality of these specific formularies as most of these have prior authorization requirements that allow for access aligned with the FILSPARI line. Ensuring that patients get access to FILSPARI quickly after receiving a patient start form is a key priority for Travere TotalCare and our dedicated patient support services team. We are pleased with the support that Travere TotalCare is providing to patients and more importantly, how these services are being appreciated by patients. This includes personalized education and assistance with the ramps and reimbursement process. Reimbursement claims undergo long and medium periods. Travere TotalCare can provide eligible patients with limited free products through the QuickStart program for up to 60 days. Our progress on these three before mentioned fundamentals resulted in net FILSPARI revenues of $3.5 million in the second quarter and a total of $6.5 million in net sales in the first four and a half months since launch, which is right in line with our expectations. As expected, revenue in the second quarter reflects a reduction in inventory from the initial stocking at the regional centers of our specialty pharmacies that was recruited in the first quarter. I'm pleased that our specialty pharmacies have since placed reorders. In looking at the overall launch through the second quarter we are really pleased. We see the strongest demand for the second quarter of launch amongst recent launches in rare nephrology and have broadened our high-quality payer access. In the second half of the year, we expect to see patient start forms growing inclusive of any seasonality in the summer months as we have seen in other recent rare nephrology launches which could result in some variability from quarter-to-quarter. We also expect to see continued successful coverage decisions that will enable us to advance access to FILSPARI. With the strong demand and broadening reimbursement we expect meaningful revenue growth for FILSPARI in the third and fourth quarters. All of this is consistent with our planning and expectations that we set forth at approval. Our progress-to-date has created a very strong foundation. And as a result we have great confidence that we will ultimately achieve our goal of FILSPARI becoming a new treatment standard for IgAN patients at risk of rapid progression and potentially meeting blockbuster sales in the future. Let me now turn the call over to Chris for the financial update. Chris?

Thank you, Peter and good afternoon everyone. As the team has highlighted, we are very pleased with the progress that has been made over the first six months of the year and we're looking forward to a strong second half still to come. Importantly, we're well-positioned from a financial perspective to support our expected growth. For the second quarter of 2023, net product sales were $57 million compared to $51 million for the same period in 2022. The increase is primarily attributable to net product sales from the ongoing launch of FILSPARI. Our legacy products also continued to perform well in the second quarter with the bile acid portfolio contributing $27.5 million in net product sales and our products contributing $26.1 million in net product sales. This growth was driven by organic patient demand. During the quarter, we also recognized $2.7 million of license and collaboration revenue, which translates to $59.7 million in total revenue for the period compared to $54.2 million for the same period of 2022. Research and development expenses for the second quarter of 2023 were $69.4 million compared to $59.7 million for the same period in 2022. The difference is largely attributable to the continued advancement of our pegtibatinase program including the ongoing COMPOSE study as well as start-up activities for the pivotal program in manufacturing. On a non-GAAP adjusted basis, R&D expenses were $62.4 million for the second quarter of 2023 compared to $54.4 million for the same period in 2022. Selling general and administrative expenses for the second quarter of 2023 were $74 million compared to $53 million for the same period in 2022. The difference is largely attributable to the onboarding the FILSPARI field team and supporting staff as well as launch-related activities including promotional support and our REMS program following the approval of FILSPARI in the first quarter. On a non-GAAP adjusted basis, SG&A expenses were $55.6 million for the second quarter of 2023 compared to $37.5 million for the same period in 2022. Total other income net for the second quarter of 2023 was $2 million compared to total other expense net of $1.5 million in the same period in 2022. The difference is largely attributable to higher interest income earned in the period. Net loss for the second quarter of 2023 was $85.6 million or $1.13 per basic share compared to a net loss of $67 million or $1.05 per basic share for the same period in 2022. On a non-GAAP adjusted basis, net loss for the second quarter of 2023 was $58.2 million or $0.77 per basic share compared to a net loss of $41.3 million or $0.65 per basic share for the same period in 2022. As of June 30th, 2023, the company had cash, cash equivalents and marketable securities of $491.3 million. As Eric highlighted earlier, we were pleased to recently enter into the agreement to sell our bile acid product portfolio to Mirum Pharmaceuticals for up to $445 million. This transaction is clear strategic and financial benefits for Travere. From a financial perspective, this transaction will bring forward several years of value from the products and meaningfully strengthen our balance sheet with an upfront payment of $210 million at close. Furthermore, we will have the potential to realize up to $235 million in additional value from sales-based milestones as Cholbam and Chenodal continue to be important treatment options for patients in the future. For the second half of the year, we anticipate our operating expenses to remain at or modestly below the levels we reported for the first half of the year, with some variability quarter-to-quarter as we continue to advance our programs and complete the bile acid portfolio transaction which is expected to close in the third quarter. Importantly, with our reported cash balance at the end of the second quarter and the expected net proceeds from the bile acid portfolio transaction we expect that we can manage our balance sheet to support operations beyond 2025, and achieve the key goals from our programs with significant growth potential. With that, I'll now turn the call back over to Eric, for his closing comments. Eric?

Thank you, Chris. I'm proud of the team's accomplishments in the first half of 2023 and the significant progress we have made towards delivering innovative treatments for patients with rare disease. We've had an outstanding start to the launch of FILSPARI, which is performing to our high expectations and on track to potentially reach blockbuster status at peak. We remain encouraged by the profile of Sparsentan in FSGS and look forward to engaging with the FDA in the near-term. Pegtibatinase data from the Phase 1/2 COMPOSE study represent further evidence of its potential to become the only disease-modifying treatment in a potential multibillion-dollar market in the future. And by entering into the agreement, to divest, our bile acid portfolio our teams will be able to further concentrate their efforts on our exciting pipeline opportunities aligning with our goal of delivering significant value in the quarters and years ahead. In the second half of the year, we look forward to providing important updates on our pipeline programs. These milestones hold the potential to make meaningful positive impacts on the lives of those impacted by rare disease and therefore, we will continue to execute with urgency. Let me now turn the call over to Naomi, for Q&A. Naomi?

Thank you, Eric. We can now open the line up for Q&A. Operator?

Thank you. [Operator Instructions] We will now take the first question from the line of Anupam Rama from JPMorgan. Anupam Rama, your line is open.

Hi. Thank you for taking my question. This is actually Malcolm Kuno on for Anupam. Just one question, what does your market research suggest about prescribing habits under the various possible scenarios of eGFR benefit? Thank you.

Malcolm thanks for the great question. And I will turn that one over to Peter.

Thanks Eric. Yeah, what I would say is, the way I would like you to think about this kind of it's a rolling launch. We started promoting FILSPARI with the PI materials only consistent to the FDA guidance that are approved through accelerated approval. Now that we are past day 120, we have the ability to promote. And as in every launch, there's an adoption curve with innovators and early adopters and this is what we plan for in our focused targeting efforts. To your question with more data we will further reinforce the FILSPARI profile and allows for new communication opportunities. And I think this will help us to further broaden the prescriber base.

Great. Thank you.

Thank you, Malcolm.

We will take our next question from the line of Tyler Van Buren from TD Cowen. Tyler Van Buren, your line is open.

Thank you. Good afternoon. Thanks for taking my question. I understand that it could take up to 20 to 60 days for patients to receive coverage. But of the 563 cumulative patient start forms that you have received. Can you say approximately how many of these are covered and then also potentially how many of them are on drug?

Thanks for the question, Tyler. And Peter, why don't you take that one?

Yeah, happy to take that question Eric. I will say as you would expect in the beginning of the launch especially this early the metrics in the fulfillment process are highly variable. If I look at where we are, I would say our metrics are right in line with benchmark in rare disease launches. And to your question on the reported 553 patient start forms, I can say that most of these patients have received FILSPARI. And we see a positive trend of conversion to paid products, that we believe will continue with increasing payer coverage decisions to include FILSPARI in formularies.

We will take the next question from the line of Greg Harrison with Bank of America. Greg Harrison, your line is now open.

Hey. Good afternoon and congrats on all the progress. And thanks for taking the question. In the prepared remarks it was noted that, you now expect the FILSPARI label to be expanded along with full approval. What do you think would change in the label? And how would that impact the addressable patient population that could get the drug?

Greg, thanks for the question. So what I would say is that, we would expect the label to reflect the full population that we studied in our Phase 3 PROTECT trial which did enroll patients one gram per day and above which is far broader than what we have in our indication statement now those patients that are at risk of rapid progression. Typically, those patients above 1.5 grams. And this was based on FDA's assessment of approval through accelerated approval. So, we do believe that there will be an expansion to reflect again the broad efficacy that we have seen at least through the interim in our Phase 3 program. And I'll have Peter talk about how that might impact the addressable population.

Yeah, I think there's two elements here. I think it helps us to further broaden how physicians think about their addressable patients. I think that's one. But I also think that there will be a broadening of the prescriber base. And I think with new data it provides further confidence that physician that may become a sense right now. And that's something that we have been planning for in our targeting efforts. I was calling out the 4500 nephrologists that we have been able to reach. We are planning to expand that further to ultimately 6,000 nephrologists and the broadening of the prescriber base with the broadening of addressable patients I think gives me good confidence for the second half of the year. And ultimately, after we have announced the data and we have the updated label that we will continue to see growth for FILSPARI in years to come.

Great. That's helpful. If I could sneak one more in how would you characterize the flow of new patient start forms throughout Q2? Was it steady or maybe accelerating towards the end of the quarter?

Yeah. Great, question. Peter would you like to take that?

Yeah, Greg. I would say, it's steadily increasing.

Yeah, I think that's right. What I would reflect is that it's increasing and we would expect as we've seen with other launches that there is variability in the first year. Importantly though Greg as we talk about what we would expect in the second half of this year would be an overall growth in both patient start forms as well as revenues given the strong demand that we've seen as well as the great expansion of payer access that will certainly reflect in growth in both of those in the back half of the year. But quarter-to-quarter or month-to-month we would expect to see some variability. But we are certainly in a great position to achieve our ambition of making FILSPARI the foundational therapy and ultimately a blockbuster medicine in IgAN.

Great. Thanks for taking the question.

We will take the next question from the line of Joseph Schwartz with Leerink Partners. Joseph Schwartz, your line is now open.

Thanks so much and congrats on the quarter. I was wondering if you could walk us through some of the powering assumptions that have gone into the PROTECT design. I think I saw somewhere that PROTECT was powered to detect a 30% difference in proteinuria after 36 weeks and also a 2.9 mL per min per year difference in total eGFR slope. And then I think you repowered the study, but then a paper came out by incur curve it all that predicted that a 30% difference in proteinuria would produce a 1.67 unit difference in total eGFR slope. And so I'm wondering since sparsentan actually produced 41% relative reduction which I think incur curve would predict to drive a 2.77 unit difference in total eGFR slope how to interpret these relationships given that companies usually power studies for smaller changes than they expect to see. And so my question, I guess is given the trials been repowered ones and some of these relationships have evolved over time. How was the trial initially powered? How do you see it being powered now? And we've heard maybe it's just with respect to FSGS that very small changes could be clinically meaningful would changes of a smaller magnitude still be possible to drive a stat sig result in PROTECT?

Yeah. Joe, thank you for the question. I think Jula is well poised to be able to provide some clarity on that question.

Yeah. Thanks, Joe. Just to clarify you're correct. We have greater than 90% power to detect a difference in slope of 2.9 mL per minute per year with 380 patients. And that's how we originally powered the trial that was based on historical data and you're correct achieving at least a 30% difference in proteinuria which we did achieve. So we now have additional data as you pointed out the interim analysis for example, our interim data and we achieved a 41% relative reduction in proteinuria, which was as you said greater than we predicted. So we did conditional power calculations based on the available interim eGFR data as well as trial-level analysis, which gave us a high level of confidence that will achieve a clinically meaningful and statistically significant effect at two years and this data did support our accelerated approval. I did want to clarify one thing is that we didn't repower, but we did over recruit. So we do continue to have a high level of confidence that we will achieve both clinically meaningful and statistically significant effects. And I will just also add that, yes, I don't think we need to hit as high based on the additional data of what we originally powered on. It's based on the treatment effect and variability. But we remain highly confident that we will hit statistical significance at two years.

Thank you very much.

We will take the next question from the line of Maurice Raycroft of Jefferies. Maurice Raycroft, your line is open.

Hi. Congrats on the progress and thanks for taking my question. I was wondering what are your latest thoughts on FILSPARI revenue for the full year 2023 as it relates to the consensus number for the year which you've commented on in the past. And also wondering separately what feedback you're getting related to REMS and REMS implementation? And how is this impacting access or PSF conversions?

Maurice, thanks for the question. Why don't I start with the FILSPARI revenue for the full year. I think we've been very pleased with what we saw in the first half. And I think with the demand that we are seeing generated launch to-date that we fully expect to see an acceleration of revenue in the second half of this year. With consensus, I think, largely in line with how other first year rare renal sales have gone, we think that we're in a good position there. So I think that we believe that we're going to see a strong second half of the year including some of the potential seasonality in the summer months that we've seen with other rare renal launches to date. So I think we're well-positioned for a strong launch. And again, this first year is really about setting the foundation for us to become a blockbuster in the foundational therapy in the treatment paradigm. I'll turn it over to Peter to give some feedback on what he's hearing in terms of REMS certification and what this means for conversions.

Yes. Happy to do so Eric. And Maurice thanks for the question. I would say, let me start by referring to the demand that we were able to generate for FILSPARI in the first half. These 563 patient start forms are generated considering the REMS program. And what we are seeing is that when the physician appreciates the strong efficacy and safety profile of FILSPARI in combination with the urgency to treat, the doctor will have the conversation with his or her patient that is at risk of rapid progression. And so I think it really comes back to focusing on the long fundamentals Eric was talking about building the foundation in the first year the first six months to nine months that we have outlined before. So this comes back to really like educating the nephrology community on FILSPARI's efficacy and safety profile and novel mode of action as well as ensuring a positive first experience. And as we mentioned in this call we plan for this and we are making solid progress in the year.

Got it. Thanks for taking my question.

Thanks, Maurice.

We will take our next question from the line of Tim Lugo with William Blair. Tim Lugo, your line is now open.

Thanks for the question and congrats on the good quarter. With the bile acid portfolio being carved out, how should we expect gross margins to trend over the next few quarters during the launch? And then maybe what will gross margins be trending at maturity?

Chris, why don't you take that question? Thanks for, Tim.

Yes, happy to do that. Thanks for the question, Tim. In terms of specifics for gross margins it will be easier for us to be able to comment on that once we've closed the transaction and we have some of the pro forma and carve out statements that will be available. But what I can point you to is that we do expect to see a reduction in expense related to the bile acid portfolio. That will come in both SG&A and R&D. And when you think about SG&A you've got a small sales force that is supporting CHOLBAM and you've got promotional efforts that go into that. So that would transition. And then from an R&D perspective, we do have a small Phase 3 study that's ongoing to support Chenodal as well as some biostats and regulatory work. And so we do expect that those expenses will transition as we move forward and we'll be able to go in a bit more detail as to the specifics on margins there as we go forward. In terms of margins for the launch, we've commented historically that we expect thus far you get to a stable state of mid- to high teens and really there at least on a gross to net perspective and everything we see thus far is in line with obtaining that.

Okay. Fair enough. And there were some comments about seasonality in the summer, but then also some destocking in Q2 and reorders which I assume would impact Q3. Can you kind of put those together it sounds like you mentioned consensus is assuming in line with the other rare renal launches. Are you pretty comfortable with what Q3 consensus is?

So Tim, what I can characterize it in the second half of the year, we do expect to see a ramp in our revenues. And I think in Q3, we do expect to see a pull-through of the demand that we were able to generate in patient start forms in Q2. And as we've seen a meaningful improvement in payer access, we think a lot of that will convert to paid scripts. But in the first part of a launch it is variable and there still is some time even with great access to be able to really tighten that correlation between demand and revenue. So we think that that's going to really start to play through in the third quarter. And then really by the end of this year we should start to see the patient start forms and revenue really tie closely together. The other thing that I will mention is that with many of the other launches within this space in their first year of launch, close to 50% of the revenues are generated in the last quarter of the year. We fully expect that that is something that we could see here. But taking a step back, I think we're very confident in our ability to meet those expectations and we're off to a strong start but we still have to continue to execute lay that foundation that Peter talked about and continue to deliver on the strong demand that was generated in the first half of the year.

Understood. Thank you so much.

Thank you.

Our next question comes from the line of Mohit Bansal with Wells Fargo. Mohit Bansal, your line is open.

Hey, this is Adam on for Mohit. What are the current areas of focus to ensure the FILSPARI launch is a success? And would start forms or sales be the better metric to watch over the next two quarters?

Yes. It's a great question, Adam. Why don't I take that one? I would say earlier in launch patient start forms are the best lead indicator. It truly is reflective of the underlying demand by patients and by physicians. And I think as we've seen that's a very strong focus. I think as we now have an increase in access and what Peter laid out in the last couple of calls is it takes about three quarters to lay that foundation for a launch like this. And so we're well positioned to do that. Once we get through that, we do expect to see meaningful uplift in revenue and that really should be then the measure of success moving forward. But I think as we demonstrated in Q2, patient start forms reflect a high level of demand out there. We expect that will continue through the rest of the year. And again, we'll be positioned to have a very successful launch in the years to come.

Great. Thank you.

Thank you.

We will take our next question from the line of Vamil Divan with Guggenheim Securities. Vamil Divan, your line is now open.

Great. Thanks for taking the questions and all the color on the call. So just maybe you can provide a little more insight on just sort of exactly which patients are getting prescribed FILSPARI. I'm trying to get a sense of sort of are the ones in the academic setting versus or in the community setting? Are they being prescribed after they get an SGLT2 before SGLT2s? Also maybe just kind of how TARPEYO is fitting into this as it being given on top of TARPEYO is there any other sort of added insights on the sort of patient profile that's being prescribed the product would be helpful. Thank you.

Great. Thank you for the question. Peter why don't you take those?

Yes. Thanks for that question, Vamil. So I think patient characteristic. I think several items I would call. I think first from a payer coverage perspective, what we said from the onset is that two-third of those patients are commercial and that is very much in line with our expectations. It's a patient population that is predominantly male. That's also in line with our expectations. I think the average age that we are seeing is in the mid-40s. But a particular question that you were asking like where does it fit in the treatment paradigm? And what we start to see is that physicians understand that this is early on as it is replacing ACEs and ARBs. Often these are rapidly progressive patients and often those patients are right now on RAS inhibition together with SGLT2. So what we are seeing is that for those patients that are being prescribed right now, it's replacing ACE inhibitors or ARBs but often in combination with SGLT2. To your other question with regards to TARPEYO, steroids in general are like a later resource but it's still on top of ACE and ARBs or now with FILSPARI that's how we see it being used as well.

Okay. Thank you.

Thank you.

We will take our next question from the line of Laura Chico with Wedbush Securities. Laura Chico, your line is now open.

Hey, good afternoon. Thanks very much for taking the question. I just had two quick ones. So first Eric, just following up on your earlier comments with respect to potential label expansion. And I think this might have been asked a little bit but are you not seeing any patients kind of below that threshold of the proteinuria indicated on the label, or is there kind of some indication that they are waiting for label expansion to begin moving into that kind of patient population set? And then just real quickly, FSGS, what are the range of outcomes that we should expect from the upcoming meeting with the FDA?

Great. Why don't I take the first one and then Jula can take the FSGS question. So we are seeing some patients that are below 1.5 grams of proteinuria, because there are other factors that physicians do determine the level of risk of progression. So we are seeing that. But as you can imagine most of the patients early in launch are the most severe, that really have very few options if any in the treatment armamentarium. So, we do expect that a label expansion will help in increasing the number of patients that would be available for us to treat, but also just the level of evidence that would be within that full approval label. So as Peter mentioned, is sort of a rolling launch with additional evidence and support moving forward. So, I think we've been pleased with the clear understanding that physicians have about helping treat patients with those parts that are at risk. And Jula, why don't you address the question about potential outcomes for FSGS?

Yes. So as we said on the call, we have a meeting with the FDA, that's scheduled. And with the DUPLEX results in hand, which we have been analyzing and as I mentioned, we released the interim data which shows durable effects on proteinuria positive trends on eGFR positive trends on kidney outcomes and then a great safety profile. We're really seeking to understanding agency's expectations for a submission and really overall willingness to accept a submission based on the totality of data that we've already released and the additional data that we have analyzed. And we do expect to be in a position to provide an update to you all later in the fall.

Thanks very much.

Thank you. Our next question comes from the line of Alex Thompson with Stifel. Alex Thompson, your line is now open.

Great. Thanks. Maybe for Peter, could you provide any color on patients and liver monitoring the setting in which the blood test is ongoing and patients may be getting a second course of therapy so far? And then maybe for Chris, could you talk about what assumptions are embedded in your runway guidance around past 2025? Thanks.

All right. Peter, would you like to take the first one?

Yes absolutely. Alex, thanks for your question. If I understand you correctly is like what is the repeat prescription of FILSPARI with like the monitoring of liver testing. What we're seeing so far the patients that have started FILSPARI that there is a high level of repeat prescription and compliance. So we don't see at this point that there is any implication or complication with the monthly liver testing. It's really on the launch, but so far on high compliance.

And Chris, the runway.

Yes, I'm happy to take that. Thanks Alex. So included in the cash runway guidance are a number of things. The first is of course the IgA nephropathy launch, second being investment in the pegtibatinase pivotal program and getting off the ground later this year. Also, baked into that is maintenance of disciplined spend for FSGS while we have those discussions with FDA and evaluate next steps. We also bring into that continued competitive dynamics for Thiola and potential pressure on that business. And then, any milestones that we would either receive and/or pay as a result of the various different programs that are going forward and sales trajectory. So, hopefully that gives you a good sense for all of what's in there.

Great. Super helpful. Thank you.

Thanks Alex.

Our next question comes from the line of Ed Arce with H.C. Wainright. Ed Arce, your line is now open.

Great. Thanks for taking my questions and congrats on the progress in the quarter. A couple for me really just to follow-up on some prior questions. First, with regard to meeting with the FDA later this year on FSGS, I wanted to get a little bit more granularity around some of the scenarios or perhaps proposals that you're coming to the meeting with, in particular whether a new trial would include more patients or higher power or perhaps a longer lead-in period or some other aspects that would better correlate proteinuria with the long-term outcome of eGFR. And then secondly, around the label expansion in IgAN, just wondering if you can put some type of a quantitative description around the incremental size of patients if you go down from the 1.5 grams now to the one gram after label expansion? Thanks so much.

Ed, thank you for the question. Maybe I can take a stab at the FDA scenarios. I think fundamentally, we're looking for FDA to align on our view that the totality of data that we've generated to date with sparsentan in FSGS would be sufficient for us to submit an sNDA. I don't really foresee that we would undertake a large trial at this point. I think that the data that we have is sufficient. Jula, would you like to add any other color to that?

I would echo what Eric had to say. And really this is our first meeting with them, them being able to see the data the totality of results that we've generated in a patient population that really has very little else available to them, and a really consistent safety profile and a consistent and durable effect on proteinuria and positive trends on many other meaningful end points. That's really just to have a first conversation to show them the data and have a discussion about next steps.

And Peter, would you like to take the question about the expanded population.

Sorry, can you repeat the question? I missed that.

Yes, the question is quantifying, how many additional patients might there be with the expanded label for IgAN at full approval?

Yes. I think it is important to realize that that even though the label is right now for patients at high risk of disease progression, generally with a proteinuria higher than 1.5. That doesn't exclude patients below 1.5, because there may be other factors why the physician determines that a patient is on a path of rapid progression. So we see also utilization below 1.5. But I think to the point that I made earlier on the call with the broadening of the label we also will see a broadening of the prescriber base, because I think that provides further confidence in the profile and opportunity for communication. And as Eric mentioned earlier, initially in the launch often you are being prescribed in patients that have not had success with any other treatment options. And as physicians start to see what FILSPARI can do and means for their own patients that stimulates repeat prescription as well. And that's what we start to hear and that's really pleasing.

Yes. I think maybe the only other thing I would add is, I think, there's going to be two factors for us assuming that the addressable population now with 30,000 to 50,000 expands given that there are up to 150,000 patients in the U.S. with IgA nephropathy. I think fundamentally, it's going to be the addressable increase of those patients that are below 1.5. And I think a very compelling data set that we now have that Jula shared from the RaDaR analysis reflects that even patients that may have been considered low risk those patients that may have 0.5 grams, there's a proportion of them that are at risk of progression. So I think there's going to be increased awareness of who's at risk as well as earlier diagnosis as we have more education in IgAN in the years to come. So, there's actually several different factors that are likely to expand the addressable population not just in the label expansion. So, we can certainly talk about that in future quarters, but we do believe that there are several meaningful factors that should expand the population moving forward.

Great. That's helpful Thank you, Eric.

Thank you.

This concludes today's question-and-answer session. I will now turn the call back to Naomi Eichenbaum for any additional or closing remarks.

Thank you. This concludes our second quarter update. We look forward to keeping you updated throughout the remainder of the year and speaking with you all again soon. Have a great rest of your evening.