Travere Therapeutics Inc

NASDAQ:TVTX

Earnings Call Analysis

Strong Growth for FILSPARI, Driving Future Potential

In the third quarter of 2024, Travere Therapeutics reported a dramatic 80% increase in product sales, totaling $61 million, propelled by the U.S. launch of FILSPARI for IgA nephropathy. Total revenue reached $62.9 million, up from $37.1 million the previous year. The recent full approval, alongside supportive KDIGO guidelines, promises a broader patient base and enhanced physician engagement. The company anticipates declining cash usage, underpinned by solid FILSPARI sales and potential milestone payments. Despite a net loss of $54.8 million, confidence remains high as patients increasingly benefit from FILSPARI, marking a pivotal growth point for the firm.

Strong Growth in FILSPARI Sales

In the third quarter of 2024, Travere Therapeutics achieved impressive financial results, with net product sales for FILSPARI reaching $61 million, a remarkable increase of approximately 80% from $33.9 million in the same quarter of 2023. This growth was fueled by the successful commercial launch of FILSPARI for treating IgA nephropathy, particularly following its full approval.

Encouraging Market Demand and New Patient Starts

Key metrics show that more than 500 new patient start forms were added during Q3, indicating continued demand, despite seasonal slowdowns typical of summer. The new patient starts have accelerated significantly since receiving full approval, enhancing optimism about future revenue growth. Travere plans to engage around 6,000 nephrologists to cover roughly 85% of the patient population at risk.

Cost Management and Operating Expenses

Total revenue for the quarter reached $62.9 million, including $1.9 million from collaborations. Tighter control over costs played a role, as Research and Development expenses fell to $51.7 million from $60.6 million year-over-year, alongside a decrease in Selling, General, and Administrative expenses. This discipline resonates well with stakeholders who value sustainable growth without compromising product development.

Financial Losses and Strategic Outlook

Despite the strong revenue performance, Travere reported a net loss of $54.8 million or $0.70 per share, a stark contrast from a net income of $150.7 million during the same period in 2023. The loss is attributed partly to the previous year’s extraordinary gain from a product sale. This highlights that while current growth is promising, the company is still navigating a challenging transition.

Regulatory Approvals and Future Potential

The company has submitted a supplemental New Drug Application (sNDA) aimed at modifying liver monitoring requirements. If approved, this could improve patient access, facilitating more streamlined healthcare processes. Further, Travere's focus on expanding FILSPARI's availability, especially in Europe, stands to significantly enhance its market presence.

Broader Market Opportunities for FSGS

Looking ahead, Travere is optimistic about its prospect for sparsentan in treating FSGS. Market data shows a direct addressable patient base of approximately 15,000 to 30,000 in the U.S., mostly served by the same prescribers as for IgA nephropathy. With ongoing discussions with the FDA and promising data from trials, particularly concerning proteinuria reduction, the potential expansion could be critical for future growth.

Embracing New Treatment Guidelines

The recent KDIGO guidelines advocate aggressive early treatment for IgA nephropathy, emphasizing medicines like FILSPARI. This shift in clinical practice presents an enormous opportunity for Travere as it strengthens its position in the market. The ability to reach out to lower-level proteinuria patients creates an expanded patient base, thereby driving further adoption of FILSPARI.

Robust R&D Pipeline and Clinical Results

Travere is dedicated to investing in research to establish FILSPARI as foundational therapy for IgA nephropathy and is also exploring its applications for FSGS. The clinical data presented at the recent ASN Kidney Week has demonstrated a significant reduction in proteinuria and stable eGFR levels, showcasing the efficacy of FILSPARI and supporting its long-term use.

Earnings Call Transcript 2024-Q3

[Operator]

Good morning, and welcome to the Travere Therapeutics Third Quarter 2024 Financial Results Conference Call. Today's call is being recorded.

At this time, I would like to turn the conference over to Nivi Nehra, Vice President of Corporate Communications and Investor Relations. Please go ahead, ma'am.

[Nivi Nehra, executive]

Thank you, Shelley. Good morning, and welcome to Travere Therapeutics third quarter 2024 financial results and corporate update call. Thank you all for joining.

Today's call will be led by our President and 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 to the Q&A session.

Before we begin, I'd 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 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, October 31, 2024, 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 Dube, executive]

Thank you, Nivi, and good morning, everyone. Our team has delivered another exceptional quarter, advancing our leadership position in rare nephrology with the full approval of FILSPARI for IgA nephropathy and the ongoing commercial launch.

As you will hear shortly from Peter, our commercial team's execution resulted in continued strength in demand, more than 30% growth in net sales over last quarter and a recent acceleration in new patient start forms following full approval and the draft KDIGO guidelines.

Our vision for FILSPARI to become foundational care in IgAN is clear and we are making great progress towards achieving this. As we look ahead, there are tangible growth drivers that we believe will enable us to reach significantly more patients with IgAN. These include the full approval label which now provides the ability to educate the nephrology community on the incredibly strong 2 year data. The updated draft KDIGO guidelines which should drive nephrologists to treat more ambitiously and use FILSPARI as foundational care and the growing body of data providing further support for earlier treatment with FILSPARI and paving the way for use in combination with other medicines.

I'm pleased to share with you, we also recently submitted an sNDA to modify the frequency of liver monitoring in the FILSPARI REMS. If this modification is approved, it represents another step forward in improving access for patients as it would align their liver monitoring with regular schedule of lab work while maintaining patient safety as a key priority.

Moving beyond IgAN, the recent recommendations of the PARASOL group offer new hope to the FSGS community. As a reminder, there are currently no medicines approved and few in development for this progressive rare kidney disease. Specifically, we were very pleased that this group of experts, including representatives from FDA, aligned around a potential proteinuria based clinical trial endpoint for FSGS. Jula will touch on this shortly, but when we look at the data from our DUET and DUPLEX studies, 2 of the largest prospective controlled studies ever completed in FSGS.

We see a statistically superior reduction in proteinuria with sparsentan compared to maximum dose standard of care across multiple proteinuria thresholds and time points. We now have a meeting with FDA scheduled where we look forward to reviewing these data in the context of the PARASOL findings. With the goal of establishing a path to an sNDA submission for an FSGS indication. We anticipate being able to provide an update on our discussions by our Q4 earnings call. In parallel, we are working diligently in preparation of an sNDA filing. If we are able to submit, we would anticipate a potential full approval for sparsentan in FSGS next year.

Lastly, we're continuing to expand access to FILSPARI outside of the U.S. with our partners CSL Vifor and Renalys Pharma. Under CSL Vifor's leadership, FILSPARI has now launched in 2 key European markets, Germany and Austria. And recently received temporary marketing approval in Switzerland. We look forward to continued progress as they launch in other countries.

Now let me turn the call over to Jula. Jula?

[Jula Inrig, executive]

Thank you, Eric. I'm pleased to provide a medical perspective following the full approval of FILSPARI and the increasing confidence we hear from nephrologists about FILSPARI's role as a foundational treatment for patients with IgA nephropathy. This confidence is rooted in FILSPARI 's compelling clinical profile as the only kidney targeted medicine which blocks 2 pathologic processes, endothelin-1 and angiotensin II.

These 2 pathways work together to amplify inflammation and kidney injury in IgA nephropathy. Our growing scientific evidence demonstrates that FILSPARI, as the only dual endothelin and angiotensin receptor antagonist, significantly reduces proteinuria and preserves kidney function for patients with IgA nephropathy.

We just attended ASN Kidney Week in San Diego, the largest worldwide gathering of nephrologists. During Kidney Week, we presented important new data supporting the use of FILSPARI in a broad population of IgA nephropathy patients at risk of disease progression, data supporting the use of FILSPARI early in treatment, as well as early data paving the way for potential combination use with other medications.

I'll briefly highlight some of these datasets. First is the SPARTAN study of newly diagnosed RAS inhibitor naive patients with IgA nephropathy, which showed that FILSPARI reduced proteinuria up to nearly 70%, with approximately 60% of patients in the study achieving complete remission through 24 weeks. And eGFR was stable throughout the measurement period. Also, as part of SPARTAN, we examined initial human mechanistic data which demonstrates that FILSPARI reduces an important inflammatory biomarker called Urinary CD163. This biomarker is recognized as highly predictive of IgAN disease progression.

The magnitude of CD163 reduction that was seen with FILSPARI has only previously been seen with a systemic immunosuppressive. These clinical data are consistent with our preclinical models and support the kidney targeted anti-inflammatory mechanism of FILSPARI. They're also promising given FILSPARI is the only non-immunosuppressive treatment available for patients with IgA nephropathy. We look forward to presenting more data from SPARTAN on how FILSPARI impacts important pathologic processes that cause kidney inflammation and injury in patients with IgAN at upcoming meetings.

We also presented promising data in patients from PROTECT with lower ranges of proteinuria less than 1 gram per gram and showed treatment with FILSPARI reduced proteinuria and preserved kidney function similarly to patients with higher ranges of proteinuria. This is especially important given the recent draft KDIGO guidelines calling for physicians to diagnose and treat all patients above 0.5 grams per day or even 0.3 grams per day. Uniquely, we also showed encouraging data on patient reported outcomes that suggests that treatment with FILSPARI versus irbesartan can improve a patient's burden of kidney disease.

Lastly, in IgAN, consistent with the growing approach of using multiple treatment options for patients with IgA nephropathy, we presented compelling efficacy and safety data in combination with SGLT2 inhibitors and immunosuppressants, both from real world use as well as from our open label extension study. We expect this will provide nephrologists with even greater confidence in using FILSPARI as foundational care.

In a late breaking session at ASN, we also presented exciting new data in high-risk subgroups of genetic FSGS patients who were historically the most difficult to treat. The data demonstrated that sparsentan was able to deliver a rapid and sustained proteinuria reduction in high-risk patients with genetic FSGS, including only a sparsentan treated patient achieving complete remission and low rates of the kidney failure composite endpoint compared to irbesartan.

The efficacy of sparsentan in patients with genetic FSGS was consistent with the overall DUPLEX population, which is promising given the subgroup of FSGS patients is typically resistant to treatment. From a regulatory perspective, we have submitted an sNDA for a modification to our REMS for FILSPARI and IgA nephropathy to request a change in our liver monitoring frequency from monthly in the first year to quarterly.

We remain confident in the safety profile of FILSPARI, especially given increased patient exposure from our clinical trials and commercial use, which continue to demonstrate no change in the low rates of asymptomatic LFT elevations and no cases of drug induced liver injury. Thus, we believe we now have the data to support the proposed change to the liver monitoring frequency within our REMS and have aligned with the FDA on the presentation of the data package for them to consider the request.

Quarterly monitoring of liver function is what was used in our clinical trials and it aligns well to the regular testing IgAN patients undergo with their nephrologist. We have requested priority review of this REMS submission with the potential for this modification to occur in the first half of next year.

Let me now turn to FSGS to discuss the recent data from the PARASOL Initiative as well as our plans for a potential sNDA submission for sparsentan and FSGS. The PARASOL Group held their public workshop in early October and we were encouraged by the input of the patient community, thought leaders, regulators and industry who came together with a common goal to identify a path forward for medicines to be approved for the FSGS community.

During the workshop, participants heard firsthand from patients and family members stories of perseverance and of hope for a better future, such as an 8 year old's wish to leave the hospital to attend his sister's third birthday. These compelling stories are a consummate reminder that the data reviewed at PARASOL are from people living with a rare kidney disease with no approved treatment options.

In our view, the PARASOL meeting was a success as the consensus from the workshop, which reviewed comprehensive analyses for more than 20 databases encompassing over 1,600 children and adults with FSGS, represent a potential new path forward for regulatory approval in FSGS. I'll walk through some of the key findings from the PARASOL work and how we believe data from our sparsentan program align. First, due to the relapsing and remitting nature of FSGS, there is clearly too much variability in eGFR measurements to remain a feasible endpoint for regulatory approval.

This was evident in our DUPLEX data set, the largest randomized study run in FSGS to date. Second, reduction in proteinuria over 24 months is strongly associated with a reduction in the risk of kidney failure in FSGS patients, including responder definitions based on thresholds of proteinuria that are both biologically plausible and strongly supported by epidemiologic data.

We have seen this response consistently across both our Phase II DUET and Phase III DUPLEX studies. In DUET, we saw significantly more patients achieve the modified partial remission endpoint with sparsentan versus irbesartan and in the open label extension portion of the study, with approximately 4 years of follow-up on sparsentan, 43% of patients achieved complete remission. Among those patients who achieved complete remission with sparsentan, which was roughly an 80% reduction in proteinuria over time, they had a significantly slower rate of loss of kidney function, approximately 1 mil per minute per year and negligible rates of kidney failure.

In DUPLEX, sparsentan demonstrated statistically significant and clinically meaningful treatment effects on the modified partial remission endpoint at 36 weeks, and this treatment effect was durable to 2 years. And as published in the New England Journal of Medicine and its supplement, we see that at multiple pre-specified thresholds of proteinuria from 1.5 grams per gram down to 0.3 grams per gram of complete remission, sparsentan demonstrated a statistically significant treatment effect versus irbesartan.

Notably, the magnitude of the treatment effect became even stronger as the proteinuria thresholds got more stringent. And while DUPLEX was not powered to show statistically significant treatment effects on heart outcomes, the rates of kidney failure were nearly double with irbesartan versus sparsentan, with a meaningful 42% reduced risk of kidney failure.

Third, there needs to be clear biologic possibility for how a potential therapy works to reduce proteinuria and/or preserve kidney function. With proteinuria as an indicator of podocyte injury, it is in the mechanistic pathway leading to kidney failure in FSGS. And in our preclinical data, some of which was recently featured in the Journal of Clinical Investigation Insight, sparsentan led to improvements in podocyte number, glomerular, hemodynamics, cell functions, and tissue repair, resulting in reduced proteinuria and preserved kidney function.

Most importantly, FDA was a key stakeholder in the PARASOL initiative and through these findings, proteinuria is now expected to be used as a validated surrogate endpoint for full approval in FSGS going forward. These data were again presented at ASN Kidney Week and were received with enthusiasm and support from the community. Overall, we believe that our data from DUET and DUPLEX align very well with the conclusions from the PARASOL group. Our next step will be to discuss our data with the FDA to understand their perspective now in the context of the PARASOL work and a potential path forward for an FSGS indication.

As Eric mentioned, we now have a meeting scheduled with the FDA and we're preparing a robust briefing book that will align with the recent PARASOL work to discuss the potential for filing an sNDA for sparsentan and FSGS. In parallel, we are preparing the sNDA, so that we will be in a position to move quickly following our FDA interaction.

I'll now briefly touch on pegtibatinase as it remains the only development program that has the potential to be disease modifying for the HCU community who deserves better treatment. While we recently announced a Voluntary Pause of Enrollment in the Phase III HARMONY Study due to necessary commercial scale up process improvements, we continue to have the utmost confidence in the program and in our team's ability to restart enrollment as quickly as possible.

We are grateful for the continued support of the HCU community and our supply partners. Overall, we've made incredible progress with FILSPARI and its path to foundational positioning in IgA nephropathy. And we look forward to our upcoming regulatory engagement on the potential to deliver sparsentan to patients with FSGS.

Let me now hand the call over to Peter for the commercial update. Peter?

[Peter Heerma, executive]

Thank you, Jula, and good morning, everyone. During the third quarter we continued our strong and focused launch execution of FILSPARI for IgA nephropathy while also preparing to build upon our success with full approval and to draft KDIGO guidelines. And I couldn't be more pleased with the strong results driven by our talented and dedicated teams.

From a demand perspective, we continued our strong growth trajectory and again added more than 500 new patients start forms during the third quarter. This is particularly noteworthy given that we encountered some seasonality as is typical during the summer holidays, as well as the fact that we took our field force out of the field for an entire week to train them on the new label after full approval on September 5th.

And I'm very encouraged with the upward inflection in new patient start forms in the weeks following full approval. As we highlighted prior to approval, we anticipated that demand would increase as physician prescribed FILSPARI to more of their patients and new physicians will write prescriptions for the first time. And we are seeing clear evidence of this coming through which provides added confidence to our outlook.

We also demonstrated continuing efficiencies in our fulfillment process while maintaining high patient compliance and persistency rates. This has resulted in $35.6 million in net product sales of FILSPARI in the third quarter representing more than a 30% gross quarter-over-quarter growth. With our execution, we continue to outperform the most recent rare nephrology launches prior to FILSPARI on all core launch metrics and we are on track to outperform these benchmarks on net revenue in the first full year of launch. We are even more excited about the opportunity ahead of us.

As I outlined during our IgAN full approval call last month, FILSPARI's new label is allowing us to further accelerate FILSPARI's growth trajectory for 2 reasons. One, we can now leverage the full potential of FILSPARI in our physician communication and educational initiatives. This is important because under accelerated approval we were limited in our commercial communication efforts to discussing only proteinuria.

But now with full approval in our compelling label, we can discuss how FILSPARI's rapid and sustained proteinuria reduction translates into superior long term kidney function preservation relative to active comparator and maximally dosed irbesartan. And this kidney preservation benefit accrues year-over-year over the course of the 2 year measurement period supporting long-term use of FILSPARI and two, the new indication statement supports broader use of FILSPARI in any adult patients with IgA nephropathy who is at risk of progression.

As a reminder, the full approval significantly expands the eligible patient population beyond the accelerated approval indication statement that guided physicians to generally use FILSPARI only in patients at or above 1.5 gram per gram. With our broader indication and the exciting data that was presented at ASN last week showing that patients below 1 gram per gram also benefit from FILSPARI. We are eager to reach these patients who can upgrade their foundational treatments.

These messages resonate well with nephrologists and are representative of what we heard from the broad community of key opinion leaders and community physicians at ASN last week. And as I mentioned earlier, we are very encouraged by the demand uptake we are seeing in the first month post full approval. The recently published draft KDIGO guidelines are already being referenced by nephrologists and expected to build further momentum. These draft guidelines emphasize the urgency to diagnose and treat patients earlier and more aggressively.

More specifically, they call for every IgAN patient who isn't in remission to be treated with a kidney targeted medicine and highlight that FILSPARI is the only medicine to have shown superiority over in trial up titrated RAS inhibition. Before handing the call over to Chris, let me share an IgAN story that exemplifies why we are so excited about the impact that FILSPARI is having on patients.

His patient recently shared in one of our national broadcasts that he looks forward to taking FILSPARI every morning because he is in complete remission and feeling great. He describes receiving his lab results as IgAN to getting an A+ on a school report card. While this is the result of only one patient and may not reflect typical results, we hear similar stories regularly and these are the types of stories that motivate our teams every day.

And we know there are so many more people living with IgA nephropathy who can benefit from a treatment that has shown superiority over maximally dosed RAS inhibition and how FILSPARI is convenient once daily oral, kidney targeted and non-immunosuppressive profile provides new hope. With our strong new label, the draft KDIGO guidelines and focused execution, we are confident in our ability to reach these patients, accelerating our growth trajectory and establishing FILSPARI as the foundational treatment option for IgA nephropathy patients.

Let me now turn the call over to Chris for the financial updates. Chris?

[Chris Cline, executive]

Thank you, Peter, and good morning. During the third quarter our execution led to a significant increase in net product sales and disciplined investments in the areas we believe will drive growth. Net product sales for the third quarter of 2024 grew to $61 million, compared to $33.9 million for the same period in 2023. This increase of approximately 80% is attributable to strong performance in the ongoing U.S. launch of FILSPARI in IgA nephropathy.

During the quarter, we also recognized $1.9 million of license and collaboration revenue which results in $62.9 million in total revenue reported for the period compared to $37.1 million in the same period in 2023. Research and development expenses for the third quarter of 2024 were $51.7 million compared to $60.6 million for the same period in 2023. On a non-GAAP adjusted basis, R&D expenses were $48.4 million for the third quarter 2024 compared to $53.8 million for the same period in 2023. Selling general and administrative expenses for the third quarter of 2024 were $65.6 million compared to $67.8 million for the same period in 2023.

On a non-GAAP adjusted basis, SG&A expenses were $49.7 million for the third quarter of 2024 compared to $51.8 million for the same period in 2023. The decline in year-over-year operating expenses is attributable to the restructuring enacted at the end of 2023 and reduced clinical expenses as the sparsentan Phase III studies advance towards completion.

Importantly, we continue to invest in evidence generation to support FILSPARI in IgA nephropathy and potentially FSGS as well as continue to invest in commercial efforts in IgA nephropathy. Now with full approval and draft KDIGO guidelines in hand. Total other income net for the third quarter of 2024 was $1.3 million compared to $3.4 million in the same period in 2023.

The difference is largely attributable to a decrease in interest income. Net loss including from discontinued operations from the third quarter of 2024 was $54.8 million or $0.70 per basic share compared to a net income of $150.7 million or $1.97 per basic share for the same period in 2023. On non-GAAP adjusted basis, net loss including from discontinued operations for the third quarter of 2024 was $35.6 million or $0.46 per basic share compared to net income of $173.5 million or $2.27 per basic share for the same period in 2023.

The difference is largely attributable to a gain related to the sale of the bile acid product which was recorded in the third quarter of 2023. As of September 30, 2024, the company, cash equivalents and marketable securities of $277.4 million, with continued growth in FILSPARI sales, measured investments including shifting some of our investments and pegtibatinase beyond 2025, we continue to expect our cash used to decline over time.

We also anticipate multiple incoming milestone payments from CSL Vifor upon conversion of FILSPARI to full approval in Europe and market access achievements. All of which continues to position our balance sheet to support current operations into 2028. I'll end with one administrative note.

Alongside the filing of our 10-Q today, we're also filing a new ATM agreement with the SEC. This is a housekeeping measure as our previous ATM which had been in place since 2020, did not transfer over to the new shelf registration that was filed in August.

With that, I'll now turn it over to Eric for his closing comments. Eric?

[Eric Dube, executive]

Thank you, Chris. I could not be prouder of the execution and performance of our organization. The underlying dynamics of our FILSPARI launch are strong and have created positive momentum for growth moving forward as a foundational therapy in IgAN. As our near-term opportunities for growth in 2025 and beyond hold great promise for the rare kidney community.

Now let me turn the call over to Nivi for Q&A. Nivi?

[Nivi Nehra, executive]

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

[Operator]

[Operator Instructions] Our first question is coming from the line of Joseph Schwartz with Leerink Partners.

[Will Soghikian, analyst]

This is Will on for Joe today. Congrats on the great quarter here. So just one for us on PSF metrics. We saw that very minor dip in numbers between the second and third quarter. And as Peter mentioned, it seems like this could be chalked up to summer seasonality and taking the sales force out for a week in September. But are there other dynamics here that we should appreciate? And how have things been trending now early in the fourth quarter? Any additional color here would be helpful.

[Eric Dube, executive]

Thanks, Will. Well, let me first say that I am incredibly impressed with what we've seen and I'll ask Peter to talk about the dynamics, particularly what we've seen since full approval. Peter?

[Peter Heerma, executive]

Yes. Thanks, Eric, and thanks, Will for the question. Let me start to say that I'm really pleased how we have continued our growth trajectory during the accelerated approval period and how we have outperformed recent rare nephrology benchmarks. To the point in what I mentioned in the prepared remarks, in Q3 we saw some typical summer seasonality and we also took the teams out of the field for a week for training for full approval.

So I'm actually really pleased with a continuation of strong growth over 500 patient start forums. But I'm mostly excited about the opportunity ahead of us and how we will accelerate momentum based on the full approval. And to what I said in the prepared remark, the demand uptake we are seeing in the first month after full approval is really encouraging and allows us to end the year strongly.

[Operator]

Our next question is from the line of Vamil Divan with Guggenheim Securities.

[Arseniy Shabashvili, analyst]

It's Arseniy for Vamil. Congrats on all your progress and thank you for taking our questions. In regard to PARASOL recommendations and FSGS, how much do you feel the discussions with the FDA will focus on hitting specific proteinuria's thresholds at certain time points? And perhaps reanalyzing the data that way versus considering the totality of data more holistically and focusing more on the mechanistic rationale and the biological visibility argument?

[Eric Dube, executive]

Great. Thank you so much for the question. Bill, I'll turn that over to you.

[William Rote, executive]

Yes. Thank you for the question, and I think it's a good one. I think you hit on the elements of what's important. Certainly based on PARASOL, the agency has said publicly that proteinuria can be used as a validated surrogate for full approval in FSGS, but the agency will always look at the full data in the submission.

So totality is important in parallel with hitting proteinuria targets. And I think additionally, as you noted, the biologic plausibility is key to the entire story, that your reduction in proteinuria in the case of sparsentan is due to the biology and the pathology of FSGS. It's a podocyte driven disease and the only way you can reduce proteinuria is to make that cell healthier and sparsentan achieves that. We have clinical data, we have preclinical data that support that. So all-in-all, you hit on 3 very key elements of this mission and I don't know how they will weight them, but we're confident that we have very strong data across that whole space.

[Eric Dube, executive]

Yes. Thank you, Bill. The only thing that I would add is that's the opportunity that we have to speak with Evan and why we're eager to meet with them here soon to be able to understand what specifically information do they want. That said, as we take a step back, we're very confident in the data that we generated in our programs.

[Operator]

Our next question is coming from the line of Anupam Rama with JPMorgan.

[Anupam Rama, analyst]

Congrats on all the progress at ASN and in the quarter. Can you give us a sense of the scope of the additional data you've provided on liver monitoring sort of beyond the clinical experience? I'm assuming that package includes all of the data from FSGS and IgAN again, clinical trial work, but correct me if I'm wrong there?

[Eric Dube, executive]

Anupam. So, Bill, why don't you take that question as well?

[William Rote, executive]

Yes. Thanks for the question. It does. Your supposition is accurate. We pulled the data from the ongoing clinical trials, the open label extensions for both DUET, DUPLEX and PROTECT. So that's an increasing body of data as well as the data that we're gaining from all of the commercial experience. So we have a substantial body of data and all of that was pooled. Importantly, what we've seen is in both the trial extensions as well as in the real world, the commercial experience, we see the same thing that we saw in the trials that low levels of LFT elevation and no evidence of Hy's Law, or liver failure events or liver injury.

So having that consistent story with a much larger body of evidence was the basis on which we built our submission to go back and change the REMS frequency to match that, that hits the cadence that patients see their nephrologists on a quarterly basis.

[Operator]

Our next question is coming from the line of Tyler Van Buren with TD Cowen.

[Greg Wiesner, analyst]

This is Greg Wiesner on for Tyler from TD Cowen. I'm curious to get some insight on what you will propose during the Type C meeting and what are the key questions you would need to ask of the FDA?

[Eric Dube, executive]

Great. Thanks so much for the question, Greg. Bill, back to you.

[William Rote, executive]

Yes. Well, I think we leverage the discussions that have been had at PARASOL where the agency has suggested a threshold of proteinuria reduction so that you have a treatment effect for both the control and the treatment arm, sparsentan versus irbesartan in our case, they haven't suggested or they haven't nailed down a specific endpoint. What they've said is you need to make a proposal and come in and talk to us. But with their presentation, they have spoken the most about the value of 0.7 gram per gram per day, patients that get below that.

So, they think that's a reasonable spot to think about when you picture what will go in and propose to the agency. And the question really is, here's our proposal, here's how we're going to analyze the data. What else do you need to see in the submission so that we're aligned with the agency and we make sure our filing has everything in it that they need for their review.

[Operator]

The next question is coming from the line of Maurie Raycroft with Jefferies.

[Unknown Analyst]

This is [ Farzin ] on for Maurie. Congrats on the progress as well. Following up on the FSGS Type C meeting, are you going to include any data from the open label extension? And then do you also on the post hoc analysis, like what would be considered like sufficient? Like is the pre-specified data already good enough or any post hoc work would be needed?

[Eric Dube, executive]

Okay, thanks so much, Farzin for the question. Bill?

[William Rote, executive]

Yes. Well the short answer for the open label extension data is yes. That will be included from both the ongoing DUET, open label as well as DUPLEX from both studies. As far as post-hoc analysis, we have threshold proteinuria cut points that were pre-specified and we looked at those as part of the statistical analysis plan and looked at in addition to FPRE or the modified partial remission, we looked at 1.5 gram per gram, [ 1.5 and 0.3. ]

So that brackets around the target that the agency has seemed to align around. We're not doing a lot of post-hoc analysis ahead of that meeting. So we will go in with the data that we have and work with them on what additional analyses they want to see in that submission and get that aligned so that we have in the file everything they need to complete their review.

[Unknown Analyst]

Yes. Thank you, Bill. And I'll point you all to our corporate presentation which is posted on our website. If you look at Slide 29, you can see very nicely laid out the treatment effect across those different pre-specified thresholds, clearly showing a benefit and superiority for sparsentan over irbesartan and FSGS. Thanks, Bill.

[Operator]

The next question is coming from Greg Harrison with Scotiabank.

[Joseph Thomas, analyst]

Congrats on the quarter. This is Joe Thomas on for Greg, just one kind of on the patient and physician education front, can you maybe comment on any ongoing efforts or opportunities you might have to help patients be getting diagnosed earlier and treated earlier based on the recent KDIGO draft guideline update?

[Eric Dube, executive]

Thanks, Joe. Peter?

[Peter Heerma, executive]

Yes, I think the presentation that Jula mentioned earlier in the prepared remarks tells about the benefit that FILSPARI has also with patients with lower proteinuria levels. And I think what I'm hearing from physicians, especially coming back from ASN, where we had many conversations with thought leaders as well as community physicians, is there is like a higher urgency and a call to action to treat patients earlier and more aggressively. And I think KDIGO really helps there. And I think we have the data now also in hand to show that FILSPARI acts consistently across different patient populations.

[Operator]

Our next question is coming from Jason Zemansky with Bank of America.

[Unknown Analyst]

This is [ Dina Ramadan ] on for Jason Zemansky, Congrats on the progress this quarter, and thank you for taking our question. Though it might be a little bit too premature to speak to FILSPARI's upside in FSGS. Could you discuss what the broader opportunity might look like? Is this something you anticipate needing to build the market, or do you think dynamics are likely to quickly shift? And maybe what sort of challenges is, is a new entrant likely to face given the lack of approved therapies, especially given the potential shift in trial endpoints?

[Eric Dube, executive]

Thanks, Dina, for the question. Peter, why don't I turn that over to you and then Jula, if there's anything further that you'd like to add on how physicians are thinking about FSGS. Peter?

[Peter Heerma, executive]

Yes. Thanks, Dina. Well, we are really excited about the opportunity for FSGS. In the U.S. in particular, the market may be slightly smaller than IgA nephropathy. We anticipate about 15,000 to 30,000 patients as directly addressable for FILSPARI. But to the point you're making, this is a patient population that is served by basically the same prescriber group as we have for IgA nephropathy. So it's basically the same call point. And if we would get like a full approval, I am expecting that we will have a rapid uptake since the brand name of FILSPARI is so well established as well as the clinical profile.

And many of the physicians have already the experience with FILSPARI in IgA nephropathy and they have seen the rapid and sustained proteinuria benefit in their patients. So I think the opportunity is real and we are really excited about it. And as I said, we have a strong position that we can build upon.

[Jula Inrig, executive]

And let me just add that remember, well, FSGS is a patient population with a really high unmet need. They have symptomatic disease, they might wake up one day, be very swollen and there's really almost nothing that is effective and safe for these patients. They get treated with immunosuppressants and if they have genetic disease that doesn't work for them. So there is a high unmet need particularly for non-immunosuppressive therapy that can reduce their proteinuria and help their symptomatology as well. So to Peter's point, it's the same physicians who are treating IgAN and FSGS. So we do believe that there is a significant unmet need here that we can address with FILSPARI.

[Eric Dube, executive]

Dina, thanks so much for the question. And certainly we recognize that there's additional education and outreach but as, as you would have heard from Julie and Peter, there's a high recognition and certainly brand awareness. We expect to be first if approved and certainly the leader and the new standard of care within FSGS. So more to come there, but certainly a tremendous opportunity for us to serve this community.

[Operator]

Our next question is coming from Laura Chico with Wedbush Securities.

[Laura Chico, analyst]

I had one on FSGS. There was some commentary at the PARASOL meeting earlier this month and just coming out of ASN now, I'm wondering if you have any thoughts on whether groups like KDIGO would consider making an update to FSGS treatment guidelines in response to the observational data that PARASOL presented.

[Eric Dube, executive]

Thanks, Laura. Jula, I'll turn that one over to you.

[Jula Inrig, executive]

Well, it's certainly potential. They typically do update if there's new treatment or there's change in where we want to target the thresholds for. There was just recently an update to those guidelines, but I would anticipate if we get full approval for sparsentan and FSGS, then that would be an appropriate time for them to make an update.

[Operator]

Our next question is coming from Yigal Nochomovitz with Citi.

[Unknown Analyst]

This is [ Reena ] on for Yigal. Thanks for taking my question. I just wanted to ask if you could comment on any compliance or adherence metrics for FILSPARI with regard to the monthly REMS monitoring, and how you might expect this rate of compliance to change with the reduction in frequency for the liver monitoring?

[Eric Dube, executive]

Thank you, Reena. Peter, I'll turn that over to you.

[Peter Heerma, executive]

Yes, thanks for the question. What we are seeing is that the compliance as well as the persistency rates of FILSPARI are really high. And I think that speaks to that patients experience that this product works for them. This is a patient population that historically has seen very little innovation. Many of the patients, every time they see their physicians, they hear you're not yet to the targets. And for the first time with FILSPARI, they are actually reaching targets. And some of those patients are in full remission, which is really encouraging for patients. And I think that's also the explanation for the high compliance and the persistency rates.

[Eric Dube, executive]

Yes. We would expect certainly that with not just the lab values but also the support and the education that these patients have, including as part of the REMS. We'd be very thoughtful around if there is a modification to less frequent monitoring that we would ensure that these patients still have the right level of support and engagement from us and from their clinicians.

[Operator]

Our next question is coming from Mohit Bansal with Wells Fargo.

[Sadia Rahman, analyst]

This is Sadia Rahman on for Mohit. So a question on the IgAN launch, given the KDIGO update recommending lower targeted proteinuria levels. Wondering if you're seeing that payers are willing to reimburse for patients that start below 1 gram. Given that your trial enrolled patients that were above that, has there been any resistance there from payers?

[Eric Dube, executive]

Thanks for the question, Peter. I'll turn that over to you. And might also be helpful to talk about how these patients are at risk based on the radar data to frame. Peter, go ahead.

[Peter Heerma, executive]

Yes, maybe Eric, to the last point, maybe it's good to start at, like patients -- according to the radar registry data set, patients reach even 0.5 gram per gram of proteinuria There is still like a 22% chance that they progress to dialysis or kidney failure by within 10 years. So this is a progressive disease. Payers are also recognizing the progressive nature of the disease and we have invested quite a bit in education for payers as well on this aspect. On your specific question with regards to like how quickly are payers adopting new guidelines as well as our new label?

Well, we have an active account team that is focusing on this. I'm really pleased with the progress we are making with payers. Some of the authorization criteria are already being updated but the majority, that's the reality is early in the year, early in 2025. But we're seeing good uptake and we also start to see that patients with lower proteinuria levels are being treated with FILSPARI.

[Operator]

Our next question is coming from Alex Thompson with Stifel.

[Charles Ndiaye, analyst]

This is Charles Ndiaye on for Alex. Congrats on all the progress this quarter. I guess from our end just wanted to ask about your current expectations for LOE in IgAN and how you see those changing in the near future?

[Eric Dube, executive]

Sure. Thanks, Charles for the question. So our current planning assumption for LOE with sparsentan is into 2033. We were very pleased to announce that we have an additional term for orphan drug exclusivity that was associated with the full approval in IgAN that would take us to September 31st. Sorry, September of 2031. So we are very pleased to have both of those layers of protection. But our current base assumption is into 2033.

[Operator]

Our next question is coming from Vamil Divan with Guggenheim Securities.

[Arseniy Shabashvili, analyst]

It's Arseniy on for Vamil. In regards to FILSPARI's IgAN launch, could you comment on your feel for the uptake with community based nephrologists versus academic thought leaders now versus when you first launched? In other words, do you feel that your message is getting out to a broader group of nephrologists now?

[Eric Dube, executive]

Arseniy, thanks for the question, Peter. I'll turn that over to you.

[Peter Heerma, executive]

Let me rephrase the question. I think the question is like, what is the uptake that you're seeing with thought leaders, academia, relatives to the community, physicians. So what we have here is, and I think it's good to -- go ahead.

[William Rote, executive]

And essentially how that changed now on the full approval versus when you first launched.

[Peter Heerma, executive]

Yes, how that changed? It's early days. I mean we are now 4 or 5 weeks post full approval. But I can give you like a broader sense on how uptake has been for FILSPARI so far. And I think it's good to realize also that you have to get a broad net to reach all the patients. And what we have said is we are planning to reach about 6,000 nephrologists out of an universe of about 10,000 nephrologists in the U.S. to be able to get to about 85% of the patient population.

So the majority of those patients are residing in the community. And that's what we also see in the prescription patterns that the majority comes from the community. Having said that, I'm really encouraged with the strong feedback that we get from academia and thought leaders about the profile of FILSPARI and in particular where FILSPARI is being positioned.

I think the recent KDIGO guidelines really outlining that you have to target the kidney as well as the immune system really resonates with physician. And what I'm hearing is that physicians really feel that FILSPARI is well positioned to be that foundational care targeting the kidney with a broad utility for a broad patient population. So hopefully that answers your question.

[Operator]

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

[Nivi Nehra, executive]

Great. Thank you, everyone, for joining us for our third quarter 2024 financial results call. We look forward to providing additional updates on our progress. Have a great rest of your day.

[Operator]

This concludes today's call. Thank you for your participation. You may now disconnect.