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spk09: You're currently on hold for this Travier Therapeutics second quarter financial results and corporate update. At this time, we are assembling today's audience and plan to be underway shortly. We appreciate your patience and please remain on the line. Thank you. Good day and welcome to the Travere Therapeutics Second Quarter Financial Results and Corporate Update. Today's conference is being recorded. At this time, I'd like to turn the conference over to the CFO, Chris Klein. Please go ahead, sir. Thank you.
spk12: Thank you, Caroline. Good morning and welcome to Travere Therapeutics Second Quarter 2022 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 Dubé. Eric will be joined for the prepared remarks by Dr. Jule Enrig, our Chief Medical Officer, Peter Hammer, our Chief Commercial Officer, and our Chief Financial Officer, Laura Clegg. 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 statement. Please see the forward-looking statement disclaimer on the company's press release issued earlier today, as well as the risk factor 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, August 4, 2022. and Travere specifically disclaims any obligation to update such statements to reflect future information, events, or circumstances. With that, I'll now turn the call over to Eric. Eric?
spk04: Thank you, Chris, and good morning, everyone. Yesterday afternoon, we provided a comprehensive regulatory update on our sparsentin and PEG-debatinase programs, which is where I will begin. First, the FDA recently communicated to us in our mid-cycle review meeting for the sparsentin, NDA, and IgA nephropathy that the review process remains on track for our PDUFA target action date of November 17th. This strengthens our confidence that we are on the path to a potential approval of sparsentin for IgG nephropathy later this year. As such, we are continuing our efforts to ready the organization for the first launch of sparsentin and I am very pleased with the progress we've made to date. The second update is that we completed our planned Type A interactions with the FDA to discuss the potential for accelerated approval of sparsentin for FSGS, and we received the final meeting minutes. Following a collaborative interaction, rather than submitting for accelerated approval this year, the FDA has recommended that we pursue traditional approval based on two-year EGFR slope data following the completion of the duplex study next year. While it is disappointing, that we will not be filing for accelerated approval this year, it does not change our belief that sparsentin has the potential to become a new treatment standard for FSGS as well as IJ nephropathy if approved. Of note, while the FDA reiterated again that we should not disclose detailed data from the ongoing study in order to assure trial integrity, they did align with us on sharing a few important elements with stakeholders. The first, is that the FDA recognizes the significant unmet need as well as the challenges in studying FSGS given its heterogeneity. There have been few clinical trials completed to date to provide insight into this disease. In many respects, we are leading the way and our duplex study is on track to deliver the largest controlled data set to date in the field. The second point is that the EGFR data since the interim analysis in the duplex study was first reported in February of 2021, we have continued to progress in a manner consistent with the profile of sparsentin. And the third is that the FDA has indicated that the duplex study as designed maintains the potential to support full approval pending completion of the study. And the FDA recommends that we pursue traditional approval based on two-year EGFR slope. These are important points as they support the fact that sparsentin is acting consistent with what we know from the history of its development and that we have confidence that the duplex study will ultimately enable us to pursue a submission for approval for FSGS. We expect to have the two-year EGFR slope and additional data available in the first half of next year. Assuming sparsentin is approved for IJ nephropathy and we see supportive two-year results from duplex, we will be in a position to submit a supplemental NDA or SNDA in the second half of next year. With this update in the U.S., we and our partners at B4 Pharma have pivoted from a joint indication submission for both IJ nephropathy and FSGS in Europe to apply for conditional marketing authorization of sparsentin for IJ nephropathy on its own this year. Pending the completion and support of data for full approval from the duplex study, we are targeting an application for approval of FSGS in Europe by the end of next year. The last update that we provided yesterday afternoon was that the FDA has granted breakthrough therapy designation to our PEG to BATNACE program for HCU. This is an exciting achievement and meaningful step forward for our program, particularly as we work to establish the biomarker pathway for a pivotal study in the US and abroad for this devastating disease. I will now turn the call over to Jula for a bit more on the regulatory updates and clinical activity. Jula?
spk06: Thank you, Eric, and good morning, everyone. I'd like to begin by recognizing the significant need for new non-immunosuppressive treatments for people living with IgA nephropathy and FSGS. We continue to hear from the nephrology community and from patients that the available treatment options are limited in their effectiveness, have a challenging side effect profile, or have long-term safety concerns. As a result, many patients are left rapidly progressing to end-stage kidney disease. We also continue to hear that nephrologists are looking to the future and seek promise for the evolution of the treatment paradigm in IgA nephropathy and FSGS. We believe that physicians will be looking to use a foundational treatment alongside other modalities to provide their patients with the greatest chance of sustained proteinuria reduction over time. We believe sparsentin as the potential first non-amino suppressive therapy to be indicated for IgA nephropathy NFSGS will become this foundational treatment if approved. I am proud of our team's execution in the second quarter. In our IgA nephropathy program, We were pleased that the NDA for sparsentin was accepted by the FDA and granted priority review. Furthermore, we were pleased with the outcome of our recently completed mid-cycle review meeting. In this interaction, the FDA indicated that the review process remains on track for our assigned PDUFA target action date of November 17, 2022, and they reiterated that they are not planning for an advisory committee to discuss the application. We have also successfully completed our onsite sponsored good clinical practice or GCP inspection. I'm very pleased with the high quality standards that our clinical and operational teams have met throughout the PROTECT study. As such, we believe we are in a strong position as we continue moving towards the target action date in November. We know that medical education is a foundational point for enabling sparsentin to become a new treatment standard. In the last six months, we've expanded our medical team to effectively deliver IJ nephropathy disease state education more broadly to the nephrology community, and we're seeing strong engagement. Additionally, we continue to work closely with the incredible patient advocacy groups in the nephrology field. Through this collaboration, we're able to provide disease state education and develop important insights into the patient journey that will help us best meet patients' needs. We also recently received clear definition on our path forward for FSGS. As Eric mentioned earlier, the FDA has recommended that we pursue traditional approval following receipt of the two-year EGFR data from the duplex study of sparsentin and FSGS, rather than pursuing accelerated approval. I'll go into some of the details of our interaction, but it's important to first highlight why we're in a situation where FDA supports accelerated approval in one indication for sparsentin, but not another. As we know, the bar for accelerated approval, which would be the first in FSGS, is high. We believe FDA is requiring a high degree of assurance with a limited data set in a patient population that's more heterogeneous and challenging to study than IgA nephropathy. In essence, we're paving the way for FSGS with the duplex study. We also have design differences between the duplex and PROTECT studies that, as we have historically talked about, are important to consider As many of you will recall, Duplex did not require a run-in period on max-tolerated ACE or ARB, and it had a two-week washout of RAS inhibition before patients received study drug. Without specifically speaking to Duplex or PROTECT, one would expect a larger change in initial EGFR with different background medications and a washout period, so this is important to note. We also know from the history of sparsentin in the Phase II duet study and experience with other ETAs that there is an initial effect on EGFR with endothelin blockade over and above RAS inhibition alone. This means when you think about total EGFR slope, which starts the measurement at baseline, you'd expect to have a larger initial difference to overcome with the washout and no run-in on uniform background medication. In our interim assessment last February, we had already established a clinically meaningful difference in proteinuria reduction. So the goal of the planned Type A meeting was to provide a more mature data cut of EGFR data and see if that met the FDA's threshold for accelerated approval. In our meeting with the agency, we shared the limited additional EGFR data that was pulled from the duplex study, which was taken at a point when all patients had been in the study for at least one year and slightly less than half of patients had been observed for two years. In order to preserve alpha in the study, we did not do any statistical analyses on the EGFR data, The data were purely descriptive in nature. As Eric highlighted earlier, since the interim analysis and the duplex study that was reported in February of last year, the EGFR data have continued to progress in a manner consistent with the profile of varsentin. This is expected and encouraging to us. However, the FDA indicated that the interim analysis conducted last year together with the recent limited additional EGFR data do not meet their threshold to support an application for accelerated approval in FSGF. Importantly, the FDA noted in the meeting and the minutes reflected that the duplex study as designed maintains the potential to support full approval pending completion of the study, and they recommended that we pursue traditional approval based on two-year EGFR slope. We expect to have those data in-house in the first half of next year, and assuming Sparcentan is approved for IgA nephropathy to be in position to submit an SNDA in the second half of next year. Finally, on sparsentin, we are working closely with our partner V4 Pharma to align our regulatory strategies for the US and Europe. Following the FSGS update from FDA, we're applying for conditional marketing authorization of sparsentin and IgA nephropathy in Europe. We anticipate a review decision in the second half of 2023 and the potential for a subsequent FSGS submission pending duplex completion in support of data, potentially by the end of next year. Our pectivatinase program continues to progress, and I'm very pleased that we recently received breakthrough designation from the FDA. This designation recognizes the significant need for new treatment options for people living with homocystinuria and the promising data that has been generated to date in the COMPOSE study. In the coming months, we're aiming to complete our discussions with the FDA and EMA on utilizing total homocysteine as an approvable biomarker endpoint. From there, we expect to engage in a multidisciplinary meeting afforded by breakthrough therapy designation to gain alignment on all aspects of our pivotal program. This approach is designed to enable us to construct a pivotal study with a high potential for success, and we look forward to the organizational commitment from the FDA as we continue to make progress. In parallel, the COMPOSE study continues to progress with patients on the highest dose of 1.5 milligrams per kilogram in the open-label extension. and with additional enrollment activities continuing for the six cohorts. We also continue to focus on working through ongoing global supply constraints to scale CMC and manufacturing for the pivotal phase of PEG2Batinase development and ultimate commercial access. Let me now turn the call over to Peter for the commercial update. Peter?
spk15: Thank you, Dula. I am pleased with the commercial organization's execution during the second quarter. We have continued to make strong progress both with the approved products and with our preparation for a potential launch of sparse sentence for IGN property later this year. During the second quarter, we saw strong demands for Tiola, but as we have talked about earlier this year, we are seeing the impact of generic dynamics affecting net sales. We expect there will be a continued downward pressure through the balance of the year as the market competition evolves. But I'm very pleased with how our team continues to identify, treat, and support patients in the Cystinuria community. The bile acid portfolio, led by demand for Colbon, performed well during the quarter. And we continue to expect growth of the bile acid portfolio in the second half of the year. Supporting Colbon is another great example of our team's ability to identify patients with rare diseases that are not always easily identified or understood. Our commercial organization is one that historically delivered year-over-year organic growth for seven consecutive years, was able to achieve more than 85% utilization of a new formulation within the first nine months of launch, and has consistently been able to provide necessary services to support patients with rare diseases. We are building upon these strengths, and we are making great strides to be ready for a potential approval of Sparcent in this fall. As an organization, there is uniform alignment and belief in the ability to achieve our vision of making sparsentient foundational therapy for patients with IgA nephropathy and FHEF as if approved. I am very pleased to report that we have completed the recruitment of our field force that will support sparsentient for IgA nephropathy at launch, if approved. I believe we have assembled a world-class team and I'm pleased to note that they have an average of almost 20 years of specialty experience, and nearly all of the clinical account managers have strong nephrology experience. We just recently had our kickoff meeting with the full field team, and I can tell you that there is great excitement about the opportunity that Spar Center may provide for patients if approved. Team members expressed that it's not often they get to be involved in the launch of a product that has the potential to become a new treatment standard. In parallel to preparing the infrastructure and team to support sparsity in the field if approved, we are also increasing our understanding of the IgA nephropathy markets through research and payer engagements. As Jula highlighted earlier, there is a significant need for new treatment options that meaningfully reduce proteinuria, allow for potential combination, and that do not have the long-term effects of immunosuppression. The results from our IgA nephropathy research and payer engagements are consistent with what we are hearing from the nephrology thought leaders, which adds confidence to our belief that the profile of sparse symptoms supports foundational use. Notably, proteinuria reduction continues to resonate as the top clinical parameter for nephrologists, and there's an increasing urgency to treat patients with IgA nephropathy who are above one gram per day. This is largely driven by the belief that if a physician can get their patients below one gram per day of profanuria, then there will be a benefit on long-term EGFR and better renal survival. Research also suggests that steroids minimization remains a key goal for nephrologists in treating their patients with IgA nephropathy and that they would use a product profile like sparsantone, potentially in combination with other treatment options if needed, to optimize the chance for the patients to reduce proteinuria and stabilize disease progression. Additionally, we have played with how the potential value proposition of sparsen and IgA nephropathy is resonating in our payer engagements. There is a strong understanding of the utility of clinically meaningful reductions in proteinuria and IgA nephropathy, especially if they're introduced before significant progressional disease. That value proposition increases when combined with a comparable safety profile to current treatment standards, such as ACE inhibitors and ARBs. Lastly, from a supply perspective, we are already positioned to ensure product availability for strong launch. Overall, we believe that the external feedback from patients, nephrologists, and patients, and payers, together with the internal strengths of our recently expanded commercial team, we will will enable us to achieve our vision of making SparCentrum the foundational therapy for patients with IgA nephropathy, if approved. The added time now between the two potential launches for SparCentrum will allow us to be incredibly focused on the best start for IgA nephropathy and also apply these learnings and experiences from the IgA nephropathy launch to have a strong launch in FHGS in 2024, if approved. I will now turn the call over to Laura for the financial updates. Laura?
spk00: Thank you, Peter. For the second quarter of 2022, we reported total revenue of $54.2 million, consisting of approximately $51 million in net product sales and $3.2 million in collaboration revenue from our European collaboration with B4 Pharma. This compares to $54.6 million in net product sales reported for the same period in 2021. As we typically see in the second quarter, growth to net discounts narrowed following the insurance coverage changes that typically impact first quarter sales. We reported a gap net loss of $67 million for the second quarter of 2022. After adjusting for non-cash expenses and income tax, we reported a non-gap net loss of $41.3 million for the second quarter of 2022. On a GAAP basis, R&D expenses were $59.7 million for the second quarter of 2022. The increase compared to 2021 is largely attributable to increased PED count as well as medical affairs activities to support the continued advancement of the sparsentin and PEG-tobatinase programs. On an adjusted basis, R&D expenses were $54.4 million for the second quarter of 2022. Relevant non-cash expenses for the fourth quarter included $5.3 million of stock-based compensation and amortization. On a gap basis, selling general and administrative expenses for the second quarter of 2022 were $53 million. The increase compared to 2021 is largely attributable to increased headcount and commercial launch preparation. On an adjusted basis, SG&A expenses for the second quarter of 2022 were $37.5 million. Significant non-cash adjustments for the quarter consisted of $15.4 million in stock-based compensation and depreciation and amortization. From an operating expense perspective, we anticipate that our R&D expenses will increase from current levels, and it may be uneven quarter to quarter as we continue to invest in ongoing clinical work and long-term supply for both sparsetin and pegtobatinase. Consistent with our planning from the beginning of the year, we expect increases in FG&A from second quarter levels as we now have the full field force staffed and continue to prepare for the potential sparsetin launch in IgA nephropathy. As we enter the second half of the year, we continue to be in a strong financial position to execute. We ended the second quarter with $553.2 million in cash and cash equivalents. Notable one-time payments made during the second quarter consisted of an $8 million milestone payment to Ligand for the NDA submission for IG nephropathy. Importantly, we believe this cash balance can support our operations into 2024, which takes into account potential further competitive pressure on Sciola investing in sparsentin launches for both IgA nephropathy and FSGS, as well as milestone payments we expect to pay related to regulatory achievements for sparsentin and pegtobatinase. As this will be my last call as CFO, I'd like to thank our incredible finance team and all of you for your continued support and engagement over the last eight years. The future at Travere remains incredibly bright, and I look forward to working closely with Chris and the rest of the management team through early next year to ensure a smooth transition. Let me now hand the call back over to Eric for his closing comments. Eric?
spk04: Thank you, Laura. Overall, we continue to execute towards our vision of being a leader in the global rare disease community. We are doing this through the continued development of our pipeline, with the objective of positioning it for sustainable, diversified growth for years to come. And by strengthening our organization to support broad access to our medications and meet the needs of patients as our products become available, we are entering the second half of the year, having made significant progress towards our goal of sparsentin becoming a new treatment standard for rare kidney disorders. The review process for our NDA for IJ nephropathy remains on track. And we are in great shape preparing the organization, and we will be fully ready to launch come November if approved. We now know that we will have to wait a bit longer for FSGS, but the fundamental value and our confidence in SparSense has not changed. We believe it is a matter of difference in time, and we will put that to good use. While we are awaiting the results of the full two-year EGFR data from Duplex, we will take the opportunity to focus even more sharply on the launch of IJ nephropathy, if approved, and applying those learnings to commercialization of FSGS in the future, if approved. Additionally, now with breakthrough therapy designation granted for PEG to batinase, we believe we will be able to efficiently align with regulators on a pivotal program that will give us the best chance of success in delivering the potential first disease-modifying therapy to a community in need of new treatments. I would like to extend one final thank you to Laura for her incredible service and leadership, and also reiterate what she said earlier. The future is incredibly bright at Travere, and I look forward to continued execution through the balance of the year. Now let me turn the call over to Chris for Q&A.
spk12: Thanks, Eric. Caroline, can we please go ahead and open up the lines for Q&A?
spk09: Thank you. If you would like to ask a question, please signal by pressing star one on your telephone keypad. If you're using a speakerphone, please make sure your mute function is turned off to reach our equipment. Once again, please press star one to ask a question. We will take the first question from the line team logo from William. The line is open now. Please go ahead.
spk02: Question and congratulations, Laura, on all your work over the past years. I wanted to just verify and be clear what two-year data from Duplex was the FDA able to look at? I know you obviously had a little bit over half of the patients at two years, but I believe you mentioned to preserve alpha, you did not run stats on these patients for proteinuria. And Also, I guess now that you're expecting a launch in IGAM with the steroid therapy already on the market, can you talk a bit about, you know, are you expecting the initial patient bullets to start sparsity and hopefully post-approval will be those that have already progressed on the P-definite therapy?
spk04: Tim, good morning, and thanks for the questions. I'll ask Bill to take the first question on what data was available for FDA, and then I'll ask Peter to talk about how we're thinking about the early uptake of IGAM once approved.
spk14: Good morning, Tim. Thanks for the question. With our agreement with the agency, there was very little done with the EGFR data, and that was a deliberate strategy to preserve the alpha for the study. So what we provided was a descriptive look at the composite of all available EGFR data for the sparsensin arm and the erbicertin treatment arm. So it wasn't broken out specifically based on, you know, those that were at two years versus those that were at one year. It was combined together, and they looked at the aggregate of that EGFR data plot, if that helps you. But it wasn't divided into specific groups based on duration in the study.
spk02: Okay, that's helpful. Thank you. Thank you, Tim, for your questions.
spk15: Shall I answer the question on your bowl so we can have an additional question to Bill?
spk02: Oh, no. I was hoping to hear from you, Peter, on the launch versus the initial bowl with the patients. Do you expect that they will be kind of failing B-definite or other steroids?
spk15: Excellent. Thanks for that, Tim. Thinking about initial uptake, there are several elements that we are taking into consideration. One of them is the relative conservative nature of nephrologists as a prescriber base in the adaptation for new treatments. We have seen it with recent introductions in nephrology. We know, for example, that they don't want to burden their office or their patients to obtain challenges. That's something that we are planning for, and we have the experience to navigate that. We anticipate launching during holiday season that requires certain challenges as well. And the first full quality that we will see for sparsity is expected in the first quarter of 2023. And that's usually also when the payers are resetting the insurance plan. So those are elements we take into consideration. We do anticipate a strong uptake once physicians gain patient experience and make it a foundational therapy for their patients. I think the attractive profile of sparsimpton that we believe resonates well with patient needs, together with our talented and experienced commercial team, gives me confidence that our mission to achieve sparsimpton as a foundational therapy is feasible and reachable. But I think given what we have seen with other uptakes in nephrology in particular, and given the timing of our launch, there may be not the initial bonus that you're talking about, but I think a faster uptake later on once patients All right, thank you for that.
spk09: Thank you. We will take the next question from line from Jeffrey. The line is open now. Please go ahead.
spk05: Hi, good morning. Thanks for taking my questions and congrats. I'll add my congrats to you, Laura, as well. Great working with you. And the question I had is you mentioned the bar for FSGS is high. Has FDA quantified what the threshold is for FSGS approval? And lastly, you mentioned you continue to see sparsity consistently. Can you elaborate on what that means?
spk04: Sure. Good morning, Maury. I'd say first I'll turn to Bill. to articulate what we understand that bar is for accelerated approval with FSGS. I think it's important for us to really highlight what we've been saying historically around the differences between these two programs with regard to the disease, the trial design, as well as the literature that supports that link in modeling the link between proteinuria and EGFR. I'll let Bill take your first question, and then I'll ask Jula to provide her perspective on that profile of sparsentin that we see consistently throughout the programs. Bill?
spk14: Yeah, certainly. Good morning, Maury. The FDA really hasn't set a specific threshold. But we do believe that that bar is high. They also, in our discussions with them, have recognized the difficulty in studying FSGS in particular. There have been very few studies done in this disease. There isn't an existing precedent, and duplex is going to be the largest data set in a controlled study in FSGS once we complete it early next year. We don't have a specific numerical threshold that they've enumerated to us. I'll hand over to Jule for some of the additional color.
spk06: Yeah, I'll comment that what's reassuring to us is barcentin is acting consistently. And you, Mari, have heard the proteinuria reduction that we've seen consistently across all the trials to date. the consistent proteinuria reduction we saw in duet in patients with FSGS, the consistent proteinuria reduction we saw in PROTECT in patients with IgA nephropathy, and in the duplex trial that we saw in patients with FSGS. The consistency that we're referring to with regards to the EGFR profile, we can't release any data, unfortunately, in the PROTECT and in the duplex trial. Obviously, the integrity of those trials, as they're ongoing, But what we can refer back to is the historical data of duet. And so we're only able to say that sparsentin is acting consistent with what we've seen historically. And what we saw historically with duet is we saw an acute decline in EGFR and then a stabilization of EGFR. And that's what we see. And that's the natural history that we see with sparsentin. And that's the mechanism of action that you would expect to see with the dual combination of endothelin and RAS blockade. And that's what gives us the consistency that we see in the profile of SARS-CoV-2 and what you would anticipate to see.
spk05: Got it. That's really helpful. Maybe one quick follow-up. Just digging into the FDA's threshold, are they more focused on the magnitude of delta between control and treatment, or are they more focused on what you see over the duration of treatment, and so that's why they want to see the two-year data for FSGS?
spk04: Bill, I'll turn that to you.
spk14: Yeah, I think it's all of those things. I think that, you know, it's effect size, it's variability, it's the duration of effect, it's a consistency of a data picture presented by all the elements of the study, proteinuria being a strong anchor on one end, but then looking across all of the data that's available and, you know, recall that with accelerated approval, it's only a partial data set, so they have less to go on. But it's not one specific element.
spk05: Got it. Thank you for taking my question.
spk04: And I think, you know, yeah, Maury, thank you for your questions. And I think it's important to reiterate that, you know, we believe that ultimately with that time completing the two years, that's going to allow us to meet that bar for full approval in an SNDA next year.
spk10: Got it. Okay. Thank you.
spk09: Thank you. We will take our next question from the line, Joseph, from SBB Securities. The line is open now. Please go ahead.
spk03: Thanks very much and I'd like to also pass along my best wishes to Laura. It was great to work with you. I was wondering if you guys could talk a little bit about the heterogeneity of FSGS some more in the context of the patients that have been enrolled in duplex. How representative of the overall population are these patients and are there any particular market segments that naturally present themselves, and would some of these be expected to be early versus later adopters of sparsantan if approved?
spk04: Joe, thanks for the questions. Jule, I'll turn that one to you, and then maybe Peter can share a little bit of the thinking as we look to ultimately the launch and what the patient population looks like. Jule?
spk06: Yeah. So, I mean, FSGS is a heterogeneous patient population and we enrolled a wide spectrum of patients with FSGS. And I think that's important to note. And, you know, this is the largest trial of FSGS patients to date. And we enrolled primary FSGS and genetic patients with FSGS and patients at risk for progression. And the spectrum included patients with a wide range of EGFR from 30 way above 90, with 20% of patients with EGFR above 90, so earlier in their disease state with regards to EGFR, but still at high risk for progression. And additionally, we enrolled a significant proportion of pediatric patients, and I think that's really important to note as well with regards to the patient population that were represented. And so just a wide range of patients, and significantly at risk for progression, and I think that's an important thing to note as well. And I'll turn it over to Peter with regards to who we think we're going to be studying here.
spk15: Yeah, thank you. Thanks for that question. I mean, we have finished our segmentation for physicians, and we are looking both at prescribe a potential amount of patients that they're treating, as well as behavioral aspects. In IgA nephropathy, what we see, other than maybe in other rare diseases where you have more centers of excellence, there is more a broader care, concentration of care in nephrology. I think it's something we have talked about historically as well. But still we see, when we look at the different deciles, there is differences in amount of patients that are seen by the nephrologist. And I think we have a good handle on that. that our focus is going to be as well, and that allows us to be very focused, and initially was launched as well, how we focus our efforts on certain centers and positions versus others.
spk03: It's very helpful. Thank you, Peter.
spk04: And maybe I can add just... a little bit more context for your questions, Joe, because I think for folks that may not be as close to this space, it'll be important to reiterate. The first is, I think, with regard to market uptake, what we are hearing from nephrologists is that based on the mechanism of action of sparsentin and the unique mechanism of action and that common injury pathway, there's a strong belief amongst nephrologists that there would be broad use across the heterogeneous FSGS population. And so we don't see that there's any particular kind of pull one way or another with regard to that segment. So we do believe that's a fundamental assumption behind our view that sparsentin will be the foundational therapy for both FSGS and IgG nephropathy. And I just want to spend a moment on what Julie mentioned in the pediatric patients and why perhaps it's important to think about that in the context of the heterogeneity and in the duplex trial. Maybe, Julie, you can speak a little bit about the EGFR profile that typically we see in pediatric FSGS patients and why that may contribute to sort of where we are today with that trial.
spk06: Yeah, certainly. You know, when we think about the broad spectrum of patients that we represented in this trial, we did have patients who were very early in their disease. And pediatric patients have really normal kidney function, really in the high range of functioning, well above 120. And within the pathophysiology of FSTS, you really want to correct that down to normal. And that's what you do when you give, whether it's an endothelin antagonist, a RAS blockade. And so you want to correct that hyperfiltration. And that's one of the common pathway injuries with FSGS that you want to correct. And that's distinct from, say, IgA nephropathy.
spk10: Thank you very much.
spk09: Thank you. We will take the next question from Greg Harrison from Bank of America. The line is open now. Please go ahead.
spk01: Good morning. This is Hao calling in for Greg Harrison. So I just had a question about the IGA nephropathy. Have you thought about pricing to balance maybe patient benefit with value, just to kind of get a sense about your sorting process and maybe some of the factors that you would consider when determining the pricing?
spk04: Yes, thank you, Hao, for the question. We have not disclosed how we will be pricing specifically yet, but I will ask Peter to share a bit of his team's thinking as we prepare for the pricing and launch in IGN nephropathy.
spk15: Indeed, and thank you, Hao, for that question. So, yeah, indeed, Eric mentioned we have not disclosed any pricing yet. We won't do that prior to launch as well. But we have studied quite a bit on the burden of disease of IgA nephropathy to make it insightful for payers, like what the cost associated with disease is today. And we know that's substantial given the progressive nature of the disease and ultimately leading to end-phase renal disease for many of those patients, often being dialysis. We've also been studying the value proposition for sparsenton, and we have disclosed some of that data earlier on, what the potential value could be of reducing proteinuria with the level that we have seen with sparsenton. And we have started engagement with payers as well in advisory boards as well as in field conversations. And I'm very pleased to see that there is a good understanding of proteinuria amongst the payer community. and there's a solid understanding as well what the value proposition of SparSentin could be. So I think that gives me confidence. It's not answering your question on the price. That's something to come. But rather than price, it always starts with, like, what is the potential value that this product provides to players and society? And I'm pleased with the conversation we're having on that.
spk04: Yeah, thank you, Peter. What I think additionally I can say, Hao, is that we do – our strategy will be to price SparSentin – for broad access given our plan to make sparsentin the new foundational therapy. And so in order for us to achieve that vision, we need to make sure that we have broad access. And we are taking a lot of the great work that Peter's team is doing on modeling the health economic benefit as well as insight from payers and the early uptake and access for others within this space. And I think we'll be in a very strong position to achieve our vision with sparsentin.
spk01: That's helpful. Thank you.
spk10: Thank you.
spk09: Thank you. We will take our next question from the line from . The line is open now. Please go ahead.
spk11: Great. Good morning. Thanks for taking the questions. Maybe just to switch it up for a second, congrats on the pectabatinase breakthrough therapy designation. I guess based on that, what should we read through to a growing alignment between you and FDA around the nature of that Phase III program and when that might be able to get started? And then, you called it out during the prepared remarks around that you didn't perform stats on the EGFR data, going back to sparsetin. I'm sure you guys considered that at some point. And having gone through the discussion with FDA, do you think that would have helped assuage some of FDA's concerns here? Any thoughts on that would be helpful.
spk04: Thank you, Carter. Bill, I'll ask you to take both of those.
spk14: So for the breakthrough designation, that allows us to have additional conversation with the agency. So once that's been granted, the agency then provides a multidisciplinary meeting where we meet with the different groups of the different review divisions, and then that spurs additional specific work on different elements of the development path. It's essentially designed such that they slide around to your side of the table and help you with the development moving forward. For us, what that means is that we're working currently on definition of surrogate endpoint, and that will continue and then working then with them on phase three trial design, what the specific data elements need to be and should be, how the pediatric patients should be included in that development, as well as aspects of manufacturing and progression of that side of it. It's an iterative process moving forward, so we really need to get through a few of those steps before I can give you better vision to to where we're starting on the phase three study and and when we've completed some of those we'll be back with with greater specificity on that and I was I'm sorry I was writing notes for the for that question as you asked your second one could could that be retraced for me please sure it was I'm sure there was can see you mentioned on you know there were no stats performed in the EGFR data consistent with prior messaging I'm sure there was consideration of
spk11: of doing some additional statistical work on that data over various points in the past year, and having gone through the discussions with FDA, do you think that, you know, do you think having done that or being able to deliver some additional data on that front would have helped assuage some of their concerns? Thank you.
spk14: Yeah, I think that's a tough one to answer. I'm not sure if it would or it wouldn't have. For us, the key was preserving alpha for the endpoint of the study. We wanted to to maintain our highest probability of success at the confirmatory endpoint, seeing that as the primary goal. So we really made the decision to do it that way in order to ensure our best chance of delivering this for FSGS patients.
spk10: Thank you.
spk09: Thank you. We will take our next question from line Laura Chico from .
spk08: Morning. Thanks very much for taking the question. Just for clarification, I'm wondering if you could just comment on study retention in both Duplex and Protect. I guess have discontinuations progressed as anticipated in both of these studies now that we've had interim updates? And then a follow-up. I just wanted to clarify, so the mid-cycle review meeting has completed with respect to IGAM, and obviously the agency has seen the interim FSGS data from Duplex, but wondering if the FSGS data could somehow trigger an amendment or how that might impact the IGAM review. I just wanted to clarify there. Thanks.
spk04: Laura, thank you for your question. Jule, can you please take the question on study retention? in Duplex and Protect? Yes.
spk10: So the studies have continued to progress with high quality.
spk06: Apologize for that. So the studies have continued to progress with very high quality. And we're seeing dropout rates within the range of what you would expect for nephrology studies of this length. And we, as you can imagine, have put a significant amount of efforts to make sure that we maintain the patients in this in both studies and so we're very proud of the efforts that we've put into this and with the retention rates that we're seeing today.
spk04: Bill, would you like to take the question on the mid-cycle review and the data availability and how that might impact FDA's review?
spk14: Certainly. The FDA throughout our development program has consistently pointed to evaluating these two programs independently and this remains the case they're different diseases they are studied on their own and they have trial designs that are different there are key differences between them that we've highlighted they did have the data sets and vision to both programs the whole way through so at the point of their mid-cycle review meeting they were aware of the duplex data and there was no expression of concern on their part as a result of those the duplex data It was in that frame that they gave us very clear feedback and that we were on track, that there was no plan for an adcom was reiterated, and that we are looking forward to our action date in November.
spk10: Thanks very much.
spk09: Thank you. We will take our last question from line Edward Nash from Kennecott. The line is open now. Please go ahead.
spk13: Hi, thanks guys for taking my question and really appreciate the clarity on the FSGS here in the States. And in Europe. I guess my question just is specific to Europe. It would just be clearly it's a risk averse to position to kind of wait for European filing also on FSGS. But just wanted to know, do you guys feel confident that it would probably turn out the same way with Europe if you went ahead and did the combined filing that the Europeans would also kind of view? view the same issue and see that increased heterogeneity would require to see data out to two years? Or is it also that just by filing together that that would risk the IGAN approval there if you have both going at the same time?
spk04: And thanks for the question. I'll turn that one over to Bill.
spk14: Sure. I mean, ultimately, our commitment here is to get sparsense into patients as fast as possible. And that remains unchanged. While we believe there is a case to be made to putting the two together in combination, we felt that that would be adding a potential incremental risk to the probability of an IGN approval and therefore risking our ability to deliver Spartan's consent to those patients as quickly as possible. You know, if the EMA were to end up with the same view as the FDA. We're now strategically aligning with our partners V4 on the regulatory process so that we have the best probability of success for both applications in Europe, and we look forward to getting the first potential approval in IGAN next year.
spk13: Great. Thanks so much. I appreciate it.
spk10: Certainly. Thanks, Ed.
spk09: Thank you. There's no further question at this time.
spk12: Great. Well, thank you, everybody, for joining us this morning for all of our updates. We have an exciting second half of the year ahead, and we look forward to sharing more updates along the way.
spk10: Have a great rest of the day.
spk09: This concludes today's call. Thank you for your participation. You may now disconnect.
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