Travere Therapeutics, Inc. Q4 FY2022 Earnings Call

Good day, and welcome to the Travere Therapeutics Fourth Quarter and Full Year 2022 Financial Results and Corporate Update. Today's conference call is being recorded. At this time, I would like to turn the conference call over to the Vice President of Investor Relations, Naomi Eichenbaum. Please go ahead, Naomi. Thank you.

Thank you, Rachel. Good afternoon, and welcome to Travere Therapeutics' Fourth Quarter and Full Year 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 Dube. Eric will be joined in the prepared remarks by Dr. Jula Inrig, our Chief Medical Officer; Peter Heerma, our Chief Commercial Officer; and Chris Cline, our Chief Financial Officer. Dr. Bill Rote, Senior Vice President of Research and Development, will join us for the Q&A session. Before we begin, I would like to remind everyone that statements made during this call regarding matters that are not historical facts are forward-looking statements within the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements are not guarantees of performance. They involve known and unknown risks, uncertainties and assumptions that may cause actual results, performance and achievements to differ materially from those expressed or implied by the statement. Please see the forward-looking statement disclaimers on the company's press release issued earlier today as well as the Risk Factors section in our Forms 10-Q and 10-K with the SEC. In addition, any forward-looking statements represent our views as of only the date such statements are made, February 23, 2023, and Travere specifically disclaims any obligation to update such statements to reflect future information, events or circumstances. During today's call, we will be covering certain financial results for the quarter and for the year ended December 31, 2022, including certain non-GAAP financial results. Please refer to the company's press release issued earlier today again, among other things, a reconciliation of the differences between the non-GAAP financial results and the most direct comparable GAAP financial results. You can access the press release on our website at travere.com. With that, let me turn the call over to Eric. Eric?

Thank you, Naomi, and good afternoon, everyone. 2022 was a year of many achievements that have further strengthened our position as a leader in the rare disease community. This is founded in our mission to identify, develop and deliver life-changing therapies to people living with rare disease. Throughout last year, we advanced our pipeline, prepared our organization for launch and continued to reach the patients that currently rely on our approved medicines. Perhaps most importantly, our work culminated in the recent accelerated approval of FILSPARI for the reduction of proteinuria in adults with primary IgA nephropathy or IgAN, at risk of rapid disease progression. FILSPARI is the first and only non-immunosuppressive medicine approved for IgA, which has demonstrated a threefold superior proteinuria reduction compared to a standard of care, irbesartan. As you heard us talk about on our recent approval call, we have high aspirations for FILSPARI as we believe it will become the foundational treatment option for IgAN patients who are at risk of rapid progression. Importantly, we have the deep market insights, the product profile, the team and the strategy to achieve that goal. If we are successful, we will be able to positively impact many patients in the U.S. with this important new medicine. We are only a few days into the launch in the U.S., but we're encouraged by the initial engagement with physicians, patients and payers and Peter will go into a bit more detail shortly. We still have more exciting milestones to come with FILSPARI in 2023. Beyond setting the launch trajectory in the U.S., we are anticipating a review decision from the EMA in the second half of 2023 for the conditional marketing authorization application for sparsentan in the treatment of IgAN in Europe. We will continue to work closely with our partner, CSL Vifor throughout the review process. And we also look forward to the 2-year data from the ongoing PROTECT study. As a reminder, the interim results from the study supported the accelerated approval of FILSPARI last week. As such, we are waiting with anticipation of the 2-year data set, which is planned for the fourth quarter of this year. Based upon the interim results, we believe the preliminary EGFR data available at the time of the interim analysis were indicative of a potentially clinically meaningful treatment effect after 2 years of treatment and that we'll be able to utilize those data for a traditional approval submission in 2024. Additionally, from sparsentan, we expect to have top line data from the 2-year endpoint in the ongoing DUPLEX study in FSGS during the second quarter of this year. If the results from DUPLEX are supportive of an FSGS regulatory submission, we would anticipate being in a position to submit an sNDA in the second half of this year and would also target submitting together with CSL Vifor for a subsequent variation to our European CMA application by end of year. This would represent an incredible opportunity for us to help patients with FSGS, one of the leading causes of kidney failure due to glomerular disease. Beyond sparsentan, we continue to advance our novel devatinase program for classical homocystinuria or HCU. Later this year, we anticipate being in position to provide additional data from the ongoing COMPOSE study as well as plans for a potential Phase III program after we complete our regulatory engagements. 2022 was a remarkable year for Travere, and I'm proud of our organization's accomplishments and perseverance that ultimately led us to our first approval from our pipeline of therapies targeting rare diseases. We have started off 2023 with a key milestone that has been years in the making, and we have much more to come as we work towards our mission of delivering life-changing therapies to people living with rare diseases. Let me now turn the call over to Jula for a clinical update. Jula?

Thank you, Eric, and good afternoon, everyone. As Eric stated, 2023 promises to be an exciting year for Travere, the rare kidney community and the patients and families impacted by IgAN. We could not be more pleased with the recent accelerated approval of FILSPARI. This milestone has created momentum in the IgAN community and set the stage for many exciting developments to come. It is important to remember that IgAN is the most prevalent primary glomerulonephritis worldwide. It is often uncontrolled, and as a result, it is a major cause of kidney failure. In fact, high-risk people living with IgAN face a median time to kidney failure of approximately 11 years. Along the way, many face pain, debilitating fatigue, depression and anxiety, as well as challenges with keeping up with everyday work life. Patients and their nephrologists are desperately seeking new treatments that can effectively reduce proteinuria and be used with less concern for limiting side effects. Right now, that's limited to ACE inhibitors or angiotensin receptor blockers, which more than 50% of patients don't respond adequately to, and SGLT2 inhibitors, which are less effective at reducing proteinuria. Steroids are also available, but are generally reserved for more severe IgAN patients because of their challenging safety and tolerability profile. FILSPARI is the only once-daily oral non-immunosuppressive medication approved for the reduction of proteinuria in IgAN. As the first of its kind, dual-endothelin angiotensin receptor antagonist, FILSPARI targets two causal pathways critical to IgAN disease progression. In the PROTECT study, we observed a rapid sustained and 3x greater reduction in proteinuria compared to while showing a consistent and tolerable safety profile similar to irbesartan. We are thankful for the FDA's accelerated approval of FILSPARI and are proud of the label we have received, which highlights the strongest clinical data demonstrated in a head-to-head Phase III study in IgAN to date. I encourage you to review the entire label at filspari.com to further understand the clinical performance, safety profile and the REMS process. A point worth noting is that both the liver and pregnancy REMS monitoring can be obtained with a single blood draw. Patients typically undergo monthly medical visits and labs, and we expect that integrating REMS monitoring into their current course of care will be seamless and serve as an effective tool for physicians monitoring their patients. Overall, we believe this label will provide nephrologists with the confidence needed to prescribe FILSPARI for their IgAN patients at risk of rapid disease progression and that this is just the beginning for realizing FILSPARI's potential. Later this year, we're expecting top line data from the confirmatory portion of the PROTECT study. If these data demonstrate a clinically meaningful benefit on eGFR after 2 years of treatment, this will further solidify FILSPARI's potential as a new treatment standard. Achieving this would enable us to submit for traditional approval with the expectation of a label that would be more representative of the total studied in PROTECT and reflect the long-term benefits of FILSPARI. Beyond IgAN, we're nearing the final results from the DUPLEX study of sparsentan in FSGS. The DUPLEX study is progressing according to plan, and we're pleased with the continued conduct and efforts to get to database lock. If the 2-year data progresses in a favorable manner, we expect to submit an sNDA for sparsentan to gain an indication for FSGS and be added to the FILSPARI label. This could be paramount for people living with FSGS as many are facing an even faster progression to kidney failure and fewer effective and safe treatment options. Beyond sparsentan, we continue to advance our pegtibatinase program in classical homocystinuria. During the fourth quarter, we completed enrollment activities in the sixth and final cohort of the ongoing Phase I/II COMPOSE study. As a reminder, pegtibatinase demonstrated dose-dependent reductions in total homocystine during 12 weeks of treatment in COMPOSE. In the 1.5 milligrams per kilogram twice weekly dose cohort, treatment with pegtibatinase resulted in rapid and sustained reductions in total homocystine of approximately 55%, resulting in the maintenance of total homocystine below a clinically meaningful threshold of 100 micromoles from week 2 through week 12 of treatment. Our sixth cohort is evaluating additional higher doses and also a lyophilized formulation that, if effective, could be utilized in a potential pivotal program and in clinical settings if approved. We remain on track for additional data from COMPOSE later this year. These data will be helpful for completing our engagement with regulators and potentially initiating a Phase III study in the second half of this year. Finally, regarding the development programs, we received Fast Track designation for our Chenodal development program in 2022. As many of you may recall, Chenodal is currently approved for the treatment of radiolucent gallstones, but it has been recognized as the standard of care for cerebrotendinous xanthomatosis or CTX for many years. Our ongoing Phase III RESTORE study is designed to provide a data set that will allow us to submit an sNDA to have the label amended to reflect what we believe is the true use of the product. We believe this could significantly aid patient identification and help people living with CTX gain earlier access to a greatly needed treatment option. We know that if CTX is identified and treated early, oftentimes, patients can go on to live a relatively normal life. We expect to have data from the Phase III study in-house this year and to subsequently submit an sNDA if the data are supportive.

Thank you, Jula. This has already been an exciting week for us. As I mentioned on the call last Friday, we built our FILSPARI launch upon our proven commercial infrastructure, which has delivered consistent results over the past eight years. We further strengthened our execution capabilities and now have a dedicated launch team with specific experience and expertise to be successful with FILSPARI. I mentioned that this team was ready to execute with a sense of urgency, and I'm pleased to report that our team has been executing very well since approval on Friday afternoon. Within one day, our materials were finalized consistent with the label in FILSPARI, FILSPARI REMS and for the total care websites were nice and operational. Even though Monday was a public holiday, our commercial field teams were excited to finish that framing and get out into the field, engaging with their customers, both nephrologists and payers. All these extensive planning and execution efforts led to the first FILSPARI prescription being written within eight business hours of approval. We anticipate this positive momentum to continue to build. To provide you a bit more context on our initial day of FILSPARI commercialization, our experienced commercial field team of more than 80 seasoned professionals is engaging in productive conversations with nephrologists and payers, focusing on the burden of disease IgAN, the challenges with the current set of care and how FILSPARI's profile could potentially address the shortcomings in the addressable population of adult patients at risk of rapid progression. The receptivity and initial interest from the nephrology community is in line with our expectations, suggesting that patients have been waiting for a product like FILSPARI. Through approval, nephrologists have consistently expressed that they need more efficacious treatment options that allow for long-term use in treating their IgAN patients who are at risk of rapid progression without the tolerability issues associated with immunosuppressive agents. We believe FILSPARI is well positioned to fill that need. It aligns with what nephrologists have been exploring over the past 30 years, built upon a common belief and routine while adding the missing component of antagonizing the endothelin. We know that endothelin and angiotensin stimulate each other and act in tandem to amplify damage to the filtration barrier in the kidney, resulting in increased proteinuria levels. Integral blocking of endothelin and angiotensin with FILSPARI has allowed for the superior efficacy relative to as observed in the interim readout of the trial. Based on FILSPARI's novel mechanism of action and robust efficacy and safety data, we are convinced that FILSPARI has the potential to become the foundational treatment option for the roughly 30,000 to 50,000 IgAN patients addressable under the current indication. It is our goal to make FILSPARI the cornerstone therapy for these patients within the evolving IgAN treatment paradigm. Lastly, I mentioned on the approval call that we have a recent product launch experience in rare nephrology, and we know that nephrologists have a largely mechanism- and data-driven approach. Therefore, our initial focus is to educate nephrologists on the FILSPARI profile, both the efficacy and safety findings as outlined in the label. Another launch dynamic that we will be navigating is the process of obtaining payer coverage. Here, I believe we are also off to a solid start. Prior to approval, we conducted extensive scientific pre-approval engagements with payers covering over 150 million lives, and we are building upon those initial conversations now. This week, we have already interacted with several national payers, and these interactions have reinforced that payers are generally well aware of IgAN and appreciate the importance of proteinuria reduction in relation to disease progression. I also referenced that we plan for an exclusive virtual experience for patients and physicians. We have established total care to help patients by offering personalized education, support in the reimbursement process and copay assistance for patients, as well as assistance for physicians with their REMS enrollments, which is typically a simple procedure. During this process, physicians will review the prescriber guide and will enhance their understanding of the label, preparing them to prescribe FILSPARI. It's also worth emphasizing that our REMS monitoring integrates seamlessly with the established REMS processes nephrologists currently use for other therapies. From a logistical standpoint, we remain on track for FILSPARI to be shipped to our specialty pharmacies next week. In summary, our execution has started according to plan, and we are well-positioned to deliver on our powerful purpose of bringing FILSPARI to patients who need it most. Turning to the performance of our in-line product portfolio in the fourth quarter of 2022, I continue to be very pleased with the execution of our commercial organization. For Thiola, we continue to see solid demand as we support the identification and treatment of cystinuria patients. This reflects our organization's inspiring way of operating and our established capabilities in the rare kidney space. We are pleased with the meaningful Thiola performance within the evolving competitive landscape. As we have talked about historically, we are seeing the impact of generic dynamics that affect net sales of Thiola, and we expect this could materialize further this year. Our bile acid portfolio continued to deliver growth in the fourth quarter. The team has a long-standing reputation for performance and dedication to educating pediatric and hepatologists. These efforts have been key to the continued growth. Our team's capability to help physicians identify patients with these ultra-rare conditions is fundamental. This expertise provides a solid foundation to build upon as we prepare for a potential future CTX indication and as we progress in our development program. In 2023, we expect to return to year-over-year growth in net product sales, while we anticipate that this will be offset by expected growth of our bile acid portfolio and the FILSPARI launch performance. As a reminder, we anticipate that FILSPARI's performance will be in line with recent benchmarks in the first 6 to 9 months. Once we gain meaningful FILSPARI payer coverage and prescribers gain their initial experiences and observe the same consistent proteinuria reduction seen in the PROTECT trial, we anticipate accelerated adoption towards the end of the year. Beyond the first year, we are well-positioned for ongoing growth of FILSPARI, which is exemplified by our ability to execute, as demonstrated with our commercial performance in 2022. This, together with the robust profile of FILSPARI and our meaningful timing advantage before traditional therapies may potentially be approved, gives us confidence that we will succeed in our strategic objective to make FILSPARI the foundational treatment for rapidly progressing IgAN patients. Let me now turn the call over to Chris for the financial update. Chris?

Thank you, Peter, and good afternoon, everyone. With the continued execution of our commercial organization and the focus on our key priorities throughout the business, we ended 2022 in a strong financial position. For the fourth quarter of 2022, net product sales were $52.3 million compared to $54.6 million for the same period in 2021. For the full year 2022, net product sales were $200.5 million compared to $210.8 million for the same period in 2021. The difference is largely attributable to a decrease in Thiola sales, partially offset by an increase in sales for the company's bile acid products. Research and development expenses for the fourth quarter of 2022 were $60.2 million compared to $62.2 million for the same period in 2021. For the full year 2022, R&D expenses were $235.8 million compared to $210.3 million for the same period in 2021. The difference is largely attributable to the continued advancement of the company's sparsentan and pegtibatinase clinical programs, including clinical trial expenses, manufacturing, and increased headcount. On a non-GAAP adjusted basis, R&D expenses were $54.2 million for the fourth quarter of 2022 compared to $57.7 million for the same period in 2021. Selling, general and administrative expenses for the fourth quarter of 2022 were $2.9 million compared to $42.1 million for the same period in 2021. For the full year 2022, SG&A expenses were $220.2 million compared to $149.9 million for the same period in 2021. The difference is largely attributable to the commercial launch preparations for FILSPARI, including having the full sales team on board and ready to launch this week. On a non-GAAP adjusted basis, SG&A expenses were $50.2 million for the fourth quarter of 2022 compared to $30.9 million for the same period in 2021. Total other income net for the fourth quarter of 2022 was $1.1 million compared to total other expense net of $4.4 million in the same period in 2021. The difference is largely attributable to increased interest income and lower interest expense during the period. Net loss for the fourth quarter of 2022 was $65.8 million or $1.03 per basic share compared to a net loss of $51.6 million or $0.84 per basic share for the same period in 2021. For the full year 2022, net loss was $278.5 million compared to $180.1 million for the same period in 2021. On a non-GAAP adjusted basis, net loss for the fourth quarter of 2022 was $49.1 million or $0.76 per basic share compared to a net loss of $37.6 million or $0.61 per basic share for the same period in 2021. As of December 31, 2022, the company had cash, cash equivalents, and marketable securities of $450.2 million. As we look to the year ahead, we anticipate that our operating expenses will continue to increase and may be variable quarter-to-quarter as we advance our programs. For SG&A, this is primarily driven by having a full year of the expanded sales team in place and our associated launch investments to position FILSPARI for success. For R&D, it is primarily driven by the continuation of both the PROTECT and DUPLEX studies of sparsentan and our work to evaluate peg treatment in combination with inhibitors while preparing for a potential pivotal program, including building supply. Accordingly, we anticipate that we can manage our balance sheet to support our operations well into 2024. This takes into account potential further competitive dynamics for Thiola, investing in launches for both IgAN and potentially FSGS, advancing pegtibatinase as well as milestone payments related to achievements for the programs. Importantly, we entered the new year with a strong financial position to support this exciting period of launch execution and the continued advancement of our pipeline to a number of key milestones in 2023. I'll now turn it back over to Eric for his closing comments. Eric?

Thank you, Chris. I want to express my gratitude to the rare disease community, the patients, their families and the Travere team for their hard work and dedication that has led us to this successful moment, the launch of FILSPARI. The strong reception by physicians, patients, and payers, even in these early days, demonstrates the value of FILSPARI in addressing the unmet need of those in the rare kidney community. We are committed to improving the lives of patients and to do so are focused on the advancement of our pipeline. In this regard, we still have a number of exciting milestones to come, including the potential approval of sparsentan for IgAN in Europe in the second half of this year and the 2-year data from the PROTECT trial in IgAN in the fourth quarter. We also anticipate top line data from the 2-year endpoints in the DUPLEX study of sparsentan in FSGS in the second quarter of this year, which could lead to an important new indication for sparsentan. And finally, we expect to be able to share more this year on our novel pegtibatinase program as we prepare for a potential Phase III program. Our years of hard work have set us up for an incredibly bright 2023. I am confident our talented team will deliver strong results for our patients and for the rare disease community. Let me now turn the call over to Naomi for Q&A. Naomi?

Thanks, Eric. Rachel, can you please go ahead and open the lines for Q&A?

We will take our first question from the line of Greg Harrison with Bank of America.

Maybe just to start off, could you walk me through the process from a patient's perspective of getting the script, enrolling in the REMS program and then the monthly maintenance testing for the REMS?

Yes, Greg, thanks for the question. Jula, maybe we'll turn to you first and you can walk through how this fits within how these patients are treated. And Peter, you can walk through what the process is for prescription and receiving FILSPARI.

Certainly. Thanks, Greg, for the question. So realize that patients who are at risk for progression are going to see their nephrologists more frequently, particularly if there's a change in their treatment algorithm. So they may see them every month with labs. As the patient is going to go see their nephrologist, they're going to discuss their overall risk of progression, having significant proteinuria as well as their eGFR decline, and the nephrologist is going to sign up for the REMS. This process for signing up for the REMS is relatively simple from both the physician’s and patient’s perspective. They need to be educated; that’s a significant part of the REMS, which means reading the label, reading the prescriber and pharmacy guide. Signing up means filling out their contact details and then signing a statement that says they're going to monitor their patient appropriately. That's the same process for a patient. They provide their contact details, state that they've been informed about the overall risk versus benefit and that they will follow the process. For a patient, what this means is that they're going to get their labs every month, and then they will receive the therapy through specialty pharmacy. I'll add one additional detail: we have just a couple of specialty pharmacies, and they will go through a similar process—reading the label, being informed to read the prescriber pharmacy guide, and then providing their contact details while attesting that they will follow this process.

Yes, let me build on what Jula said and thanks, Greg, for that question. Before giving you a little more detail on the mechanistics of the total care patient services, I think it's good to realize the high need for these patients, and that's the reason why we have accelerated approval in the first place. We have to realize that this is a younger patient population and it's often diagnosed in the late teens or early 20s. A hard proportion of those patients progress to kidney failure within 11 years, as Jula mentioned in previous remarks. So that means that many of those patients will end up in dialysis in the midst of their productive lives. When we talk about the REMS and the early responses we have seen so far, and this is still early days—it’s only day four of promoting FILSPARI—but early responses from nephrologists confirm that they don’t have alternative treatment options today for these patients as they have with FILSPARI. Once nephrologists understand the efficacy and safety profile of FILSPARI, they appreciate the simple procedure of the REMS enrollment and focus back on the clinical value that FILSPARI may have for their patients.

Great. That's really helpful. And then could you remind us how many IgAN patients are treated by community nephrologists and how this has influenced your launch strategy?

So the vast majority of those patients are being treated by community nephrologists, and we have plans for that as well. That's why I mentioned in the call last week that we will be consistently reaching out to about 6,000 nephrologists to cover about 85% of the patient potential.

When you did your most recent market research at the end of last year and asked about intent to prescribe in 6 months or a year post-launch, I'm wondering if you tested key aspects of the label in the market research.

Thanks, Maury, for that great question. Peter, would you like to take that?

Yes, absolutely. Thanks, Maury, for that question. We have done consistent market research, and that has been consolidated by external research, for example, by syndicated market reserve. It was quite surprising to me that the intent to prescribe did not change after we announced the liver monitoring REMS, and the intent to prescribe remained at 90%. I just saw a result actually this week of the latest profile of the label, and again, the intent to prescribe came in at 88%. So it’s been very consistent at around 90% prescription in the first year, and about 70% intent to prescribe in the first 6 months. So they didn’t really change meaningfully.

Got it. And Peter, you highlighted some of the plans around doctor education efforts. Can you talk about where the most challenging learning curves will be? And how will you message around eGFR to doctors?

Yes, absolutely. I mean it's early days—it's only day four—but what we see so far from what I'm hearing from our field reps is there is great excitement for the promise of FILSPARI. In fact, I got a text yesterday from one of our reps, who has been in the field for 30 years, saying that he has never seen this level of excitement among nephrologists. So I think there is a certain level of excitement to learn about the profile of FILSPARI, and proteinuria is often the marker that physicians are measuring on a monthly basis and also how they monitor progression of disease and how they change their treatment plan. So the conversation around eGFR has not come up yet in many of those conversations. They understand that it's an ongoing trial and are very excited to learn more about the FILSPARI profile over time.

I have a question on IgA nephropathy and then FSGS. So how do you expect the rate of FILSPARI uptake to differ, if at all, amongst patients treated at academic versus community nephrology centers? And beyond those segments, are there any other particular physician demographics that you expect to be earlier or later adopters?

Joe, thank you very much for the great question. Peter, I'll pass that over to you.

Yes, very timely question, Joe, because this was also part of the market research I was just referencing. I saw that yesterday. Very interestingly, the utilization and intended utilization for FILSPARI is basically similar across community nephrologists as it is in academic nephrology. So we will see how that materializes over time, but the intent to prescribe is quite similar among the two specialty categories.

Thanks, Peter. Maybe if I could just add, Joe, one of the things that we are reflecting in our launch plans, and Peter's team has done a fantastic job, is really helping to understand not just those 6,000 targets but also the segments to make sure that we recognize which physicians have adopted recent innovation more quickly—the early adopters versus late adopters. Our team is making sure that we're very much focusing our efforts in the first part of launch on those clinicians that we would see as early adopters, similar to many other launches. So I think it's not just about academic versus community, but it's also a number of patients and their behaviors, such as adoption of recent rare renal launches.

If I may build on that, Eric, I just mentioned that we will be consistently calling on about 6,000 nephrologists. To give you a little more context on how we got to those 6,000, it's really based on three different segmentation and targeting assessments that we did. One was based on patient volume, the second was based on behavior, in particular on new product utilization, to identify the early adopters. The third was their influence in the nephrology community. We have a very clear way to target and segment those physicians that we see as most valuable in the prescription process to get to that broad patient population.

A question on the Phase III DUPLEX study in FSGS. When we look at or think about the eGFR slope, the 108-week data readout, could we use the DUET extension study and the slope that was calculated for there as a good estimate? And when you calculate the slope of the eGFR curve, what time points do you look at? I know for DUET, you were looking starting at day 42 to week 108; just wanted to know where the starting point is.

Thanks for the question. I’d say we certainly do feel that there is a parallel between what we have seen in DUET and what we expect to see and how we designed DUPLEX. I'll turn the question to you on how we might expect to see the slopes for sparsentan but also perhaps natural history given that we didn't have a long-term follow-up of an active comparator in that trial.

Yes. I think the long-term data that we've received from DUET shows kidney preservation compared to what we would expect to see in the long term for patients who are at high risk of progression with primary FSGS. I would say historically, those patients can progress more at a rate of greater than 5 ml per minute; more like 7, 8, 9, 10 mls per minute per year, and we saw less than that in our long-term eGFR data that we presented last year at ASN. In particular, in patients who achieve complete remission, we saw significant preservation in those patients regarding long-term eGFR slope. I don't know if there's any additional granularity you'd like me to provide around that.

I think most of my questions have been answered. But I guess I would just ask what the level of confidence is for a good outcome in the upcoming FSGS final data? Maybe you could just explain that level of confidence. Are you highly confident, kind of hopeful but moderate, not so confident? Just curious on how you're thinking about it. We're getting a ton of questions on FSGS these days.

Sure. Yes, Liisa, thank you very much for the question. We certainly are excited about this upcoming data readout next quarter. I would say that we remain confident in the outcome, and that's largely because the way that we designed the trial was based on showing a robust and statistically significant superiority on proteinuria. That would predict out to eGFR. As we've looked at the way the trial is conducted and the number of patients that we've retained in the trial, all of those considerations we look at to ensure that the study is being conducted as we had hoped are present. I’ll turn it over to Jula; maybe Bill, if you have any further thoughts on why we remain confident and what would constitute a good outcome from the 2-year results.

Yes. I'll just continue on with what Eric was saying. We see a clinically capable and statistically significant separation and reduction in proteinuria with sparsentan versus irbesartan. Importantly, when we met with the FDA, they said the study is designed to support traditional approval. This also helps reinforce our confidence in achieving our goals. We have powered the study appropriately and continue to retain a significant number of patients to achieve our endpoint separation or demonstrate the treatment effect on eGFR. Bill, do you want to chime in regarding regulatory perspective?

Yes. I think when I think about it from a regulatory perspective, this is Bill. The FDA approaches accelerated approvals very deliberately and somewhat conservatively because you have a partial data set for both safety and efficacy. At the end of the study, with a traditional approval, the totality of data will be considered, and I think that puts it in a different frame from a regulatory standpoint when compared with an interim analysis under Subpart H accelerated approval.

Thank you, everyone, for joining us for our fourth quarter and full year 2022 financial results and corporate update call. We look forward to an exciting year ahead and providing updates on our progress along the way. Have a great rest of your day. Thank you for joining.