Travere Therapeutics, Inc.

Thank you, Shelly. Good morning and welcome to Terea 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 Enrich, our Chief Medical Officer, Peter Hearmont, our Chief Commercial Officer, and Chris Klein, 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'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 statement. Please see the forward-looking statement disclaimer on the company's press release issued earlier today, as well as the risk factors section in our forms 10-Q and 10-K filed with the SEC. In addition, any forward-looking statements represent our views only. As of the dates that statements are made, October 31, 2024, interviewer specifically disclaims any obligation to update such statements to reflect future information, events, or circumstances. With that, let me now turn the call over to Eric.

Thank you, Nivi, and good morning, everyone. Our team has delivered another exceptional quarter, advancing our leadership position in rare nephrology with the full approval of Silspari 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 Cadego guidelines. Our vision for PhilSparry 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 two-year data. the updated draft CADEGO 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 am pleased to share with you, we also recently submitted an S&DA 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. Jule will touch on this shortly, but when we look at the data from our duet and duplex studies, two of the largest prospective controlled studies ever completed in FSGS, we see a statistically superior reduction in proteinuria with sparsentin 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 Paracel findings with the goal of establishing a path to an SMDA 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 SMDA filing. If we are able to submit, we would anticipate a potential full approval for Sparsentin in FSGS next year. Lastly, we're continuing to expand access to PhilSparry outside of the U.S. with our partners CSLv4 and Rinalis Pharma. Under CSLv4's leadership, PhilSparry has now launched in two 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?

Thank you, Eric. I'm pleased to provide a medical perspective following the full approval of PhilSparry and the increasing confidence we hear from nephrologists about PhilSparry's role as a foundational treatment for patients with IgA nephropathy. This confidence is rooted in PhilSparry's compelling clinical profile. as the only kidney targeted medicine which blocks two pathologic processes, endothelin 1 and angiotensin 2. These two pathways work together to amplify inflammation and kidney injury in IgA necropathy. Our growing scientific evidence demonstrates that filfari 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 Vilspari in a broad population of IgA nephropathy patients at risk of disease progression. Data supporting the use of Vilspari 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 data sets. First is the SPARTAN study of newly diagnosed RAS inhibitor naive patients with IgA nephropathy, which showed that SILSPARI 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 SILFARI reduces an important inflammatory biomarker called urinary CD163. This biomarker is recognized as highly predictive of IGAM disease progression. The magnitude of CD163 reduction that was seen with SILFARI has only previously been seen with a systemic immunosuppressive. These clinical data are consistent with our preclinical model 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 one 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 CADIGO 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 suggest that treatment with Filspare versus Erbisartan can improve a patient's burden of kidney disease. Lastly, in IgM, 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 Silspari 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 sparsentin was able to deliver a rapid and sustained proteinuria reduction in high-risk patients with genetic FSGS, including only a sparsentin-treated patient achieving complete remission and low rates of the kidney failure composite endpoint compared to erbisartan. The efficacy of sparsentin 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 SMDA for a modification to our REMS for filspari and IG 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 REM 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 IGAM patients undergo with their nephrologist. We have requested priority review of this REM 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 SMDA submission for sparsentin 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 eight-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 from 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 SPAR-CENTEN 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 duets and phase three duplex studies. In Duet, we saw significantly more patients achieve the modified partial remission endpoint with sparsentin versus erbisartan. And in the open-label extension portion of the study, with approximately four years of follow-up on sparsentin, 43% of patients achieved complete remission. Among those patients who achieved complete remission with sparsentin, which was roughly an 80% reduction in proteinuria over time, they had a significantly lower rate of loss of kidney function, approximately one mil per minute per year, and negligible rates of kidney failure. In duplex, paracentam demonstrated statistically significant and clinically meaningful treatment effects on the modified partial remission endpoint at 36 weeks, and this treatment effect was durable to two years. And as published in the New England Journal of Medicine and its supplement, we see that multiple pre-specified thresholds of proteinuria from 1.5 grams per gram down to 0.3 grams per gram are complete remission. For a sentence demonstrated a statistically significant treatment effect versus erbicartin. 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 erbisartan versus sparsentin, with a meaningful 42% reduced risk of kidney failure. First, 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 Insights, Barsentin led to improvements in podocyte number, femoral 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 SSGS 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 Parafel 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 SMDA for sparsentin in FSGS. In parallel, we are preparing the SMDA so that we will be in a position to move quickly following our SDA interaction. I'll now briefly touch on PEG-2-Batinase 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 in enrollment in our 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 sparsension to patients with FSGS. Let me now hand the call over to Peter for the commercial update. Peter?