Earnings Call Transcript - TVTX Q1 2022

Chris Cline, Senior Vice President of Investor Relations

Good afternoon. And welcome to Travere Therapeutics First 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 Dube. Eric will be joined for the prepared remarks by Dr. Jula Inrig, our Chief Medical Officer; Peter Heerma, our Chief Commercial Officer; and our Chief Financial Officer, Laura Clague; Dr. Bill Rote, Senior Vice President of Research & 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 factors section in our Forms 10-Q and 10-K filed with the SEC. In addition, any forward-looking statements represent our views only as of the date such statements are made, May 5, 2022 and Travere specifically disclaims any obligation to update such statements to reflect future information, events or circumstances. I'll now turn the call over to Eric. Eric?

Eric Dube, CEO

Thank you, Chris, and good afternoon. I'm very pleased with our progress to start 2022. During the first quarter, we made significant headway on our key priorities of advancing our pipeline of potential first-in-class treatments for people living with rare disease and preparing our organization for potential launches of sparsentan if approved. Most notably during the quarter, we achieved an on-time submission of our new drug application or NDA for accelerated approval of sparsentan in IgA nephropathy. We look forward to receiving notice later this month from the FDA regarding the acceptance of the NDA, as well as the timeline for review. If the NDA is accepted and we are granted priority review, we would anticipate a launch in IgA nephropathy as early as the end of this year if sparsentan is approved. We are also on track to submit additional eGFR data from the ongoing DUPLEX study to the FDA this quarter. We will be providing an update following our regulatory interactions, but we will not be providing incremental updates before then. As a reminder, we believe the potential outcomes include the FDA being supportive of a submission for accelerated approval for FSGS. In which case, we will be preparing to submit an NDA under Subpart H in the coming months or that the FDA recommends that we instead wait until full completion of the study in the first half of next year, and we would subsequently expect to submit for full approval in 2023. Together with our European partner, Vifor Pharma, we also remain prepared to submit a combined IgA nephropathy and FSGS MAA submission for conditional approval of sparsentan in Europe, pending alignment with the regulatory path in the U.S. I’m also pleased with the further positive reception of the data from our ongoing Phase 1/2 COMPOSE study of pegtibatinase, following its presentation at SIMD last month. Pegtibatinase represents an exciting potential new treatment for people living with classical homocystinuria or HCU. And we look forward to continuing to progress our discussions with regulators on the design of a pivotal program. On the commercial side of the business, our first quarter performance was strong and in line with expectations in a challenging environment. As many of you will recall during our end of year update, we outlined that in 2022, we do not anticipate overall growth in net product sales due to the generic dynamics for Thiola. Our first quarter performance is consistent with that guidance. Demand across all products in the quarter increased. In fact, we are seeing a return to pre-pandemic levels for overall demand and the bioasset portfolio continues to perform well. But as expected, the dynamics for the evolving competitive landscape in cystinuria are beginning to put pressure on the net revenue from our Thiola business. This shift is accounted for in our planning and I continue to be incredibly impressed by our team's ability to maintain continuity of the business and support for the patient community despite these challenges. Notably Peter and the commercial organization continued to do a fantastic job of building upon the strengths and expertise of our current sales team in nephrology to prepare for a launch of sparsentan in the U.S. as early as the end of the year if approved. As a result of our progress to-date both in the clinic and from a commercial preparation perspective, I remain confident that if approved, sparsentan can become a new treatment standard for the many patients with rare kidney disease currently facing a rapid progression to dialysis. Finally, during the quarter, we strengthened our financial foundation through the convertible refinancing transactions enacted in March. These transactions resulted in us being able to effectively extend the maturity on the vast majority of our convertible notes from 2025 to 2029, and add modest incremental cash to the balance sheet. Let me now turn the call over to Jula for a clinical update. Jula?

Jula Inrig, Chief Medical Officer

Thank you, Eric and good afternoon. I'm pleased to report that in the first quarter we advanced all of our clinical programs. For sparsentan, the most notable achievement during the quarter was a submission of an NDA for accelerated approval in IgA nephropathy. And looking at the IgA nephropathy treatment paradigm, there's a desperate need for novel non-immunosuppressive treatments. Physicians are currently treating patients with IgA nephropathy with RAS inhibitors and steroids in an attempt to reduce proteinuria, delay the progression to dialysis, and avoid the need for transplantation. If possible, what we've seen for many years is that the available treatments are limited in their effectiveness or long-term safety. Many patients are still progressing at a rapid pace to end-stage kidney disease. If sparsentan is ultimately approved, it has the potential to be the first non-immunosuppressive treatment indicated for IgA nephropathy and is believed to become foundational therapy for the future. The NDA submission in March was a critical step on the path to potentially delivering sparsentan to patients and physicians. Given the significant unmet need in IgA nephropathy and the strength of the data from the PROTECT study, we requested priority review in our submission. We expect to receive a response on the acceptance of the submission and a review timeline later this month. If priority review is granted, we would expect a PDUFA action date and potential approval as early as November of this year. We look forward to working with the FDA throughout the review process. We also remain on track to provide the FDA with additional eGFR data from the ongoing DUPLEX study and FSGS this quarter. As Eric outlined earlier, we will provide an update once we've had our regulatory interactions. Consistent with our plans, since our Type A meeting last year, should the additional eGFR data meet the agency's requirements for accelerated approval, we will be in a position to quickly submit an NDA for FSGS as well as a joint MAA submission with our European partner, Vifor Pharma. I'm pleased that both DUPLEX and PROTECT, two of the large studies year-to-date and FSGS and IgAN respectively, continue to progress and remain on track for their completion next year. Finally, we continue to be excited about the potential for pegtibatinase to become the first disease-modifying approach to homocystinuria. In April, we had the opportunity to present detailed results from the first five cohorts of the Phase 1/2 COMPOSE study at the SIMD annual meeting for 2022. The data including rapid and sustained decreases in homocysteine and methionine and achieving mean homocysteine levels below 100 micromole demonstrate that pegtibatinase can improve overall metabolic dysfunction and support proof-of-concept for pegtibatinase as a potential treatment for HCU. Throughout the presentations of the data, engagement with KOLs, patient leaders and an advisory board held in conjunction at SIMD, we received uniformly positive feedback on pegtibatinase's potential in HCU and invaluable insights to incorporate into our pivotal program planning. Patients from the first five cohorts in the COMPOSE study are continuing in the open-label extension and we're continuing enrollment activities in the sixth cohort. The continued advancement of the COMPOSE study is designed to build upon the strong initial data set as we plan for the next phase of development. In parallel, we're advancing our discussions with regulators on a pivotal program while working through ongoing global supply constraints to scale CMC and manufacturing for the pivotal phase of development and commercial access. We are pleased with our progress on both of these initiatives, and we look forward to providing additional updates later this year. Let me now turn the call over to Peter for the commercial update. Peter?

Peter Heerma, Chief Commercial Officer

Thank you, Jula. We continue to see great execution from our commercial organization, which is particularly encouraging as we move closer to the first potential launch of sparsentan if approved. The first quarter of the year has had the highest number of new patients initiating our therapies since the first quarter of 2020. We believe this is a result of our team's continued efforts, increased access to engage with prescribers and patients visiting deposition again, more regularly. Despite the increase in new patients initiating therapy, we did see a slight decline in net product sales compared to the same period last year. This is driven by generic dynamics affecting Thiola, which is consistent with our expectations and business planning. As we guided in the beginning of the year, we expect further pressure on Thiola through the balance of the year that we will work to continue identifying new patients and continue to support the cystinuria community. Notably in the first quarter, our bile acid product experienced 14% organic growth over the same period last year, primarily driven by the team's execution with Cholbam. While we often see uneven performance with the bile acid products due to the ultra-rare nature of the conditions they treat, this was a particularly strong quarter for Cholbam, which we believe is a testament to our Cholbam suite’s continuous engagements. We continue to expect modest growth of the bile acid products in 2022, which is expected to partially offset the generic impact on Thiola. Most importantly, our performance is within our expectations to start the year, and it continues to demonstrate our ability to identify and treat patients with rare diseases. Furthermore, it provides added confidence in our planning and execution as we prepare for the upcoming potential launches of sparsentan if approved. As we move ahead through the balance of 2022, we will leverage our nephrology goal points to develop a deeper understanding of those physicians who treat patients with IgA nephropathy and FSGS, and we will continue to focus on the three key areas we outlined at the outset of the year, working with our medical team so they can provide helpful disease state education, advancing the compelling value proposition to payers, and expanding our established commercial infrastructure to be ready to support the launches if sparsentan is approved. I continue to be very pleased with our progress. For example, we have already hired senior leadership – senior sales leadership with extensive rare and nephrology experience. And we have incredibly strong demands from high-quality candidates for our field-based roles to ultimately support sparsentan. Altogether, we remain confident that we will be in a position to enable sparsentan to become a new treatment standard in rare nephrology if approved. I will now turn the call over to Laura for the financial update. Laura?

Laura Clague, CFO

Thank you, Peter. For the first quarter of 2022, we reported total revenue of $48.5 million, consisting of approximately $46.4 million in net product sales and $2 million in collaboration revenue from our European partnership with Vifor Pharma. This compares to $47.4 million in net product sales reported for the same period in 2021. As has been typical for us in years past, we did experience higher gross-to-net discounts in the first quarter, driven by insurance coverage changes in the beginning of the new year. As we move through the balance of the year, the gross-to-net discounts are expected to narrow but will continue to be higher than in previous years for the Thiola business. We reported a GAAP net loss of $76 million for the first quarter of 2022. After adjusting for non-cash expenses and income tax, we reported a non-GAAP net loss of $51.6 million for the first quarter of 2022. On a GAAP basis, R&D expenses were $56.6 million for the first quarter of 2022. The increase compared to 2021 is largely attributable to the ongoing studies of sparsentan as well as advancements of the pegtibatinase program in HCU. On an adjusted basis, R&D expenses were $53.2 million for the first quarter of 2022. Relevant non-cash expenses for the fourth quarter included $3.5 million of stock-based compensation and amortization. On a GAAP basis, selling, general and administrative expenses for the first quarter of 2022 were $46.8 million. The increase compared to 2021 is largely attributable to increased headcount and commercial launch preparations. On an adjusted basis, SG&A expenses for the first quarter of 2022 were $35 million. Significant non-cash adjustments for the quarter consisted of $11.8 million in stock-based compensation and depreciation and amortization. From an OpEx perspective, we anticipate that our R&D expenses will continue to run at a rate slightly higher than in the first quarter. This is representative of the ongoing DUPLEX and PROTECT studies that will continue into 2023, as well as the ongoing COMPOSE study of pegtibatinase and foundational work, including scaling CMC, to prepare for a pivotal program. Consistent with our planning from the beginning of the year, we expect increases in SG&A from the first quarter level, as we continue the commercial build-out, including additions to our field team for the potential sparsentan launch in IgA nephropathy. Importantly, we continue to be in a strong financial position to execute in 2022 and beyond. We ended the first quarter with $603.4 million in cash and cash equivalents. This balance includes approximately $19 million in net proceeds from our at-the-market facility, prior to our convertible transaction in the first quarter and approximately $95 million from the convertible refinancing transactions enacted in March. Taken into account, the potential impact of further competitive pressure on Thiola, milestone payments we expect to pay related to regulatory achievements for sparsentan, but not yet factoring in the full pivotal program for pegtibatinase, as that is still being planned out. We anticipate this cash balance will support our planned operations into 2024. Let me now hand the call back over to Eric for his opening comments. Eric?

Eric Dube, CEO

Thank you, Laura. Last month, we announced that after spending more than 30 years in the biopharmaceutical industry and more than seven years as CFO of Travere, Laura has decided to retire so that she can spend much-deserved time with family. I would like to take this opportunity to thank Laura for her unwavering dedication to our mission and her contributions in making Travere into a leader in the rare disease community. As a result of Laura's leadership, we have developed an outstanding finance team and a strong financial foundation. We are very pleased that Chris will be taking over the CFO role in August. His capital markets experience, deep institutional knowledge, and strategic vision will be ideally suited for the role. We look forward to him continuing to work closely with the investment community as we enter this new phase of growth. Overall, I am very pleased with our execution to start the year. Most importantly, we have continued to progress towards our goal of making sparsentan a new treatment standard for rare kidney disorders if approved. With the on-time submission of our NDA for IgA nephropathy, we have furthered our commercial preparations to be ready for a potential launch as early as the end of this year. We remain on track for our planned FDA interactions regarding the eGFR data from DUPLEX and the accelerated approval pathway in FSGS. Together with the continued advancement of our pegtibatinase program and the strengthening of our balance sheet during the quarter, we are well positioned to continue our execution throughout the balance of 2022. Let me now turn the call over to Chris for Q&A. Chris?

Chris Cline, Senior Vice President of Investor Relations

Great. Thanks, Eric. Justin, can we go ahead and please open up the lines for Q&A?

Unidentified Analyst, Analyst

Hi, all. This is Will on for Joe, and thank you for taking our questions today and congrats on recent progress. So one question for us in terms of the overall IgAN market, there's obviously a relatively large addressable patient population here, but we're curious who the early adopters would be of something like sparsentan. Is it something with those with higher proteinuria or are there other segments that are important for physicians in the company to target as you approach the potential launch in the fourth quarter? Thank you.

Eric Dube, CEO

Well, thanks for that great question. I will ask for Peter and Jula to give their thoughts on where we might assume the early uptake for sparsentan. Peter, maybe you can start and then Jula maybe you can add your perspective.

Peter Heerma, Chief Commercial Officer

Yes, absolutely. Well, we've spoken about how we see the IgA nephropathy market. I think the total market is about 130,000 to 150,000 patients, the way we are thinking about like what is the addressable patient population at launch for sparsentan. We have indicated that's about 30,000 to 50,000, and those are the patients that are seen by the nephrologists that have a confirmed IgA nephropathy diagnosis through a biopsy, and that have consistently high proteinuria levels. Those are seen as the patients that are on a rapid path of progression. So those are the patients that we will be focused on initially.

Unidentified Analyst, Analyst

Great. Thank you. And if I could just sneak in one quick follow-up. We recently saw another sponsor in this space report some interim data with another ETA inhibitor, also for IgA nephropathy. So just wondering kind of how you're thinking about the competitive landscape moving forward with potentially multiple players in this market?

Eric Dube, CEO

Sure. I'll ask Jula to give her perspective on that. I think it's an important caveat that those are very early interim data, but Jula, maybe you can pick up on there and where you believe sparsentan will be well positioned if approved.

Jula Inrig, Chief Medical Officer

Yes, there remains a significant unmet need for treatment of IgA nephropathy, and we believe that nephrologists will ultimately be seeking out new treatment options. Patients remain at very high risk with the current treatment options we have, which is ACE inhibitors or ARBs. We believe sparsentan therapy with the significant reduction in proteinuria that we saw with PROTECT, a 50% reduction in proteinuria, will become foundational therapy if it's approved. Yes, there are a number of other therapies in development. We believe sparsentan will be foundational therapy, and some of the other niche therapies can potentially be additive to that.

Unidentified Analyst, Analyst

Excellent. Thank you again, and congrats on the progress.

Eric Dube, CEO

Thanks.

Carter Gould, Analyst

Good afternoon, and then best of luck to Laura and congrats to Chris on the new role. I guess, the first question is around understanding that we're not going to see any eGFR data from PROTECT anytime soon. Are there plans to share or publish the data that you've shown already and maybe additional secondary analysis or baseline characteristics before a potential launch? It's been – I guess, close to 260 days since we got the top line, and we still haven't seen any other kind of data. And then beyond sort of the eGFR data in FSGS, are there any other data you'll be providing to the FDA as part of that next go-round in terms of conversation? Thank you.

Eric Dube, CEO

Yes, Carter, thanks for the questions. The answer to both of those is that we are going to prioritize managing the blind and the integrity of the study until it is completed in the first half of next year. Any additional data beyond the interim analysis on proteinuria, which was the primary endpoint at that point, could potentially increase the risk of unblinding, trial integrity. As we've discussed repeatedly in the past, that's really an area of focus for the FDA. So we're balancing that very carefully and making sure that we do everything possible to complete the study with a robust data set. As such, we do not have plans to publish any additional data at this point. For the interim analysis on eGFR that we're meeting with FDA later this quarter, we do not have any additional analyses beyond that update to eGFR. We want to make sure that we are doing as minimal look as possible based on what FDA would like to see, anything beyond that may actually compromise the unblinding within the company or with sites and could compromise our ability to maintain alpha for the final analysis. At this point, we do not have plans for additional analysis or disclosure of additional data beyond what we have to date.

Carter Gould, Analyst

All right. Thank you.

Eric Dube, CEO

Thank you.

Greg Harrison, Analyst

Good afternoon. This is Mary Kate on for Greg. Thank you so much for taking our question. Maybe just a question in regard to the potential of sparsentan launch in IgAN if approved. What are your expectations for the cadence on the initial uptake in ramp-up of sparsentan in IgAN, and maybe what are your expectations regarding reimbursement?

Eric Dube, CEO

Mary Kate, thanks for the questions. As you can imagine, that is right. The area of focus for Peter and his team, it is a bit early in terms of us talking about that, but our goal is to make sure that we have a very strong launch and that sparsentan does become the new standard within IgAN and FSGS after that. In order to do so, we need to have broad access within those populations. I'll ask Peter to talk a little bit more about early expectations as his team is working on those.

Peter Heerma, Chief Commercial Officer

Yes, very good. Thank you, Mary Kate. It's too early to give specifics on how we see the large uptake, but I think what we are seeing very consistently in our own research, as well as syndicated research, and external research being done, also among the investor community, we see a very consistent trend: physicians feel very excited about the opportunity, the mechanistic mode of action of sparsentan. To claim that as foundational therapy because to Jula’s earlier point, many of those patients remain untreated to the target that physicians would like to see. So, with this in mind, we think that sparsentan can really play a role, especially considering the new KDIGO guidelines that were presented last fall. With regards to your other question on access, we are very pleased with the interactions we've had with payers and the response we're getting from them. They see the unmet need, they recognize the unmet need, and there is a high interest regarding new modalities and innovative treatment. So I think we are making good progress. We are building a very solid value proposition, so more to come, but so far, I think we are very pleased both with the feedback from physicians and from the payer community.

Eric Dube, CEO

I think that's right, Peter. Thank you for that. And Mary Kate, the only thing that I would add is that we certainly recognize that nephrologists are conservative by nature and very much focused on understanding the clinical evidence and the mechanism of a treatment. That very much is part of how we're planning to prepare to give them the information and the tools to help make the best decision for these patients once approved.

Liisa Bayko, Analyst

First congrats for your – the progress. And my question is, how well will the eGFR data in FSGS and subsequent FDA decision affect the MAA submission in Europe?

Eric Dube, CEO

Thanks for that question. Our focus is to make sure that we understand the position of the FDA and what our timelines would be for an FSGS submission before we change any plans we have in place. Nothing has changed in our plans to date. We are on track to provide a combined MAA in the middle of this year. The statement that I mentioned around it's going to be after, there may be information that FDA provides that helps us to think through before anything that may affect. But at this point, we don't see any of that. We've not yet met with the FDA and our plans have not changed in our timeline for MAA.

Liisa Bayko, Analyst

Thank you. And if I can add one more question, can you provide some color on your collaboration with PharmaKrysto? What is your rationale and how does it fit into your portfolio?

Eric Dube, CEO

Sure. We're really pleased about this opportunity. It is early and it is an asset or program that we believe is well suited within our rare nephrology expertise. This asset is a potential one that is pre-IND. We're not discussing much at this point, but it is something that over the next couple of years, we see the potential for an IND and continuing to progress for development. We will certainly share more information when we get to that point, and we're excited because it's another opportunity for us to support the rare nephrology community.

Maury Raycroft, Analyst

Hi, thanks for taking my questions and congrats on the progress. You disclosed some patient baseline characteristics from the IgAN PROTECT study in the ERA conference abstract. Just wondering if you can help contextualize what's disclosed in the abstract and maybe talk about what the FDA is going to be focused on with comparing and contrasting your drug with cholestasis, Tarpeyo, to determine what the label should ultimately look like?

Eric Dube, CEO

Sure. I'll ask Jula to take the first question, which is providing context for the baseline data, and then I'll ask Bill to share what the FDA may be looking for.

Jula Inrig, Chief Medical Officer

Sure. We are excited to share our baseline characteristics at ERA from both DUPLEX and PROTECT independently. They're both the largest interventional trials testing a novel therapy in IgAN and FSGS. What we think is really important is that both studies are representative of the planned patient populations. We are excited to share this data with the nephrology community and each of the populations are unique. You can see that represented when you look through the abstracts and that we cover those patient populations representatively.

Bill Rote, Senior Vice President of Research & Development

I'll take the second question. Thanks for the question, Maury. I think the heart of it is compare and contrast sparsentan versus budesonide. The potential impacts on that eventual labeling, of course, it's speculation at this point. If you look at benefit risk, which is where the reviewers will start with any of the steroid class, the risk profile is very different from what you see with sparsentan, where we have a high degree of tolerability such that it's a long-term therapy that other therapies would be added upon. I would hope that there would be a broader label than what was provided to Tarpeyo. Certainly, most of my experience with the agency has been based around the premise of you get what you study. We'll need to wait and see based on the review. It's going to come down to benefit risk and I’m very confident in the position that sparsentan has in that arena.

Maury Raycroft, Analyst

Got it. That's helpful. And do you think there will be some restrictions on proteinuria based on baseline characteristics? Or is it tough to say at this point?

Eric Dube, CEO

It's very difficult to say at this point.

Maury Raycroft, Analyst

Okay. Maybe a last quick question. Just on since sparsentan is a first-in-class dual ARB and ERA blocker. Can you talk about chances of getting an AdCom and remind what feedback you’ve gotten on the potential for an AdCom so far?

Eric Dube, CEO

Sure. Bill, would you like to take that?

Bill Rote, Senior Vice President of Research & Development

Certainly, we don't expect to have an advisory committee. We ask the question during our pre-NDA meetings, and their answer was no, with what we know now, we don't anticipate having an advisory committee that could certainly change. If it does, we'd be prepared for that, but it's a very clear picture. Strong data, it's not the type of package where the agency would normally request an advisory committee. So we're confident in their first answer that no, they don't intend to have one.

Maury Raycroft, Analyst

Got it. Okay, thanks for taking my questions.

Eric Dube, CEO

Thanks, Maury.

Tim Lugo, Analyst

Thanks for the question and congratulations to Laura on the career, as well as Chris on the new role. Briefly I guess some questions on pegtibatinase. Can you talk about these global supply chain issues? Are they impacting the end of Phase 2 meeting, or do you need to complete the six cohorts before your next FDA interaction? And can you also remind us how the formulation, the sixth cohort is different from the formulation used in the other five?

Eric Dube, CEO

Sure. Tim, I will hand those over to Bill.

Bill Rote, Senior Vice President of Research & Development

Certainly. Thanks Tim. With the challenges that we're seeing in the manufacturing space, I think they're not so much specific to pegtibatinase but are endemic within all biologics manufacturing. You have a combination of a flexing of the supply chain to manage a lot of COVID vaccine manufacturing around the world, which took up manufacturing slots and made them more challenging to obtain, and it consumed a lot of raw materials and consumables. We’re making good progress on the manufacturing side, but it's important for us to let stakeholders know that these are challenges that we've been navigating. Regarding your second question about the formulation difference for Cohort 6, this is the first cohort that will be using a lyophilized formulation. Cohorts 1 through 5 used a liquid formulation that for stability reasons was frozen at very low temperatures. By going to the lyophilized formulation, it makes the overall handling and the material shipments and the supply of clinical trial material much easier.

Eric Dube, CEO

Thanks Bill. I think the only thing that I would add, Tim, just on that question of supply challenges is these are not new. These are ones that we've shared in the past. Bill's team is making great progress, and we don't believe has any bearing yet on the timing of our interactions with the FDA. We're making good progress with those interactions.

Tim Lugo, Analyst

Okay. And maybe I could ask a broader question kind of giving your current cash position and what we're seeing as kind of wide overall weakness in the market, which everyone's aware of. Does that change your thinking around bringing in additional assets? Pegtibatinase seems to be a good transaction. I'm sure there are some other assets out there.

Eric Dube, CEO

Yes, it's a great question, Tim. I'll start and then certainly I'll ask Laura to provide anything further. We continue to look at opportunities that are out there. There is a lot of weakness within the marketplace. We know that there are companies that may have issues moving their assets in rare disease forward. That said, we also want to be very mindful about our use of cash and be sensitive to any potential dilution, particularly before we get sparsentan out there and have a successful launch there. So our number one goal remains the successful launch of sparsentan. We're doing all we need to invest in that, but it's not going to slow down our diligence and monitoring of that landscape. Laura, is there anything else that you'd want to add?

Laura Clague, CFO

No, I think you covered it well, Eric. Really our position on cash, as we mentioned on the call, is we do believe our cash will last into 2024. To your point, that really is completing any additional business development work, but to Eric’s point, there do seem to be a little more undervalued opportunities these days. You never know, there could be a good fit out there, but nothing planned right at this point.

Eric Dube, CEO

Yes. I think the only other thing I would add is PharmaKrysto is a good example where, with very little cash investment, this could be an important area within the rare renal space. Again, it's early, but it's a reflection that we're going to continue, but we're going to be very responsible and disciplined in the use of our cash and any business development activities.

Unidentified Analyst, Analyst

Hello, this is Michael on from Michelle. Congrats on the quarter, just a couple more questions on pegtibatinase. So what is the path forward with pegtibatinase? How has your engagement with regulators been regarding moving forward based on a biomarker versus perhaps clinical outcomes, and what would you need to show on any secondary functional endpoints?

Eric Dube, CEO

Great. Thank you, Michael, for the questions. Bill, maybe you can take the question on how's that going the engagement with regulators and biomarker, and maybe Jula, if there's anything else you'd want to add about secondary endpoints that you're hearing from the specialist community.

Bill Rote, Senior Vice President of Research & Development

Certainly, the path forward is going well. We are in what is essentially an iterative dialogue with the agency around various aspects of the program, CMC, endpoints, trial design, etc. When we get to a point where we've completed enough of that, we'll update on the overall package. Your specific question around biomarker versus clinical endpoint: This is an ideal disease for the use of a biomarker as a clinical endpoint. We're working with the agency and following their guidance on how to qualify total homocystine as the appropriate endpoint for that. Those efforts are underway. If you wanted to use a clinical endpoint in this disease space, it would be very challenging because the time scale of these changes are longer than what traditional pivotal clinical trials are. There's just a mismatch in the duration of what would be required. It really is an ideal setting, and there is precedent from the 90s for a drug approved using total homocysteine as a biomarker.

Jula Inrig, Chief Medical Officer

As Bill mentioned, the disease is very slowly progressive. Some of those secondary endpoints would be collected as patients would be in our studies, but they develop over many years. Clinical endpoints such as ocular effects or thrombotic events would be collected over many years, not as part of homocysteine direct lowering over a short-term. Eventually, patients would want to be able to liberalize their diet, which would be the ultimate goal over the long term, and we'd hope to capture some of that information eventually.

Unidentified Analyst, Analyst

Excellent. Thank you. Just one more quick one on pegtibatinase. How does the IP look – how long do you anticipate an exclusivity period? Thank you.

Eric Dube, CEO

Yes, so we do have a patent family for pegtibatinase, but the simplest approach and most robust would be for the exclusivity period granted for a biologic orphan disease product. So you can assume 10 plus years for that, and then 12 years in Europe.

Laura Chico, Analyst

Good evening. Thank you very much for taking the question. I just have two. First in FSGS, one of your competitors announced they'll pursue a single pivotal study in a genetically defined FSGS population, but the endpoints they're focusing on are eGFR slope and change in proteinuria. So I'm just wondering, with a broad lens, could you comment on the robustness of FPRE as a surrogate measure and maybe how you see the FSGS regulatory landscape changing over time?

Eric Dube, CEO

Certainly, I'll ask Jula to add anything further, because her work before joining the company certainly involved a lot of foundational work tying robust measures of proteinuria to long-term renal outcomes. That really is the foundational element of FPRE. It is a robust measure of proteinuria reduction and is using some of the largest registries of FSGS patients correlated with longer-term renal survival and eGFR. That was a strong component of why we chose FPRE and are confident in that being a high bar for proteinuria function. There is another program in clinical development. It is in a subset of FSGS patients. But fundamentally it’s the same focus of measuring proteinuria, aligning with nephrologists' treatment focus as well as long-term eGFR, which is very important to regulators. Jula, would you add anything on the profile of sparsentan making it a foundational therapy?

Jula Inrig, Chief Medical Officer

Yes, FPRE is more aligned with how we think of FSGS, a disease in which you're looking at remission. It is a measure of proteinuria and patients getting to a certain threshold and magnitude of reduction. It captures that. As Eric said, it is the measure, which has the strongest correlation with protecting eGFR, preserving kidney function, and delaying time to dialysis or transplantation. It has the greatest correlation. It’s ultimately a measure of reduction of proteinuria, so it is consistent with the other trial. This is why we believe sparsentan can be foundational therapy: sparsentan blocks endothelin and angiotensin receptor in a single molecule, reducing proteinuria, delivering a combined mechanism in one molecule.

Eric Dube, CEO

Yes, I think that’s right, Peter, thank you for that. Jula, the only other thing that I would add is that we certainly recognize that nephrologists are conservative by nature and very much focused on understanding the clinical evidence and the mechanism of a treatment. That very much is part of how we're planning to prepare to give them the information and the tools to help make the best decision for these patients once approved.

Skuyler, Analyst

Hi, this is Skyler on for Do Kim. Thank you for taking my question. I was wondering if you get approval in both IgAN and FSGS, how are you thinking about pricing when you consider the different dosing levels of the indications, or FSGS could be two times the dose of IgAN. I'm curious if you could provide any color around your thoughts regarding that. Thank you.

Eric Dube, CEO

Sure. Thank you, Skyler, for the question. I'd say largely, it's early for us to talk specifics around pricing. That said, there's a lot of work that we are doing to assess the burden of illness and the health economic aspect of sparsentan. Our overall strategy for pricing and reimbursement approaches is to ensure broad access within the label populations to make sure that patients can benefit from sparsentan, ultimately, that’s the way that we will be able to achieve our vision of sparsentan being the foundational therapy.

Peter Heerma, Chief Commercial Officer

I think you’ve covered it well, Eric. There are different disease states and also FSGS is generally seen as a more progressive disease. Your point about the dose difference is well taken when considering pricing. It's also important to consider the burden of disease. All those aspects we take into consideration before we make a pricing decision. Our initial launch will be in IgAN, and we already have a competitor there. So that allows for some flexibility with more to come based on the data we are gathering right now.

Ed Arce, Analyst

Hi, thanks for taking my questions. And let me add my congrats to both Laura and Chris. A couple of questions for me, firstly on pricing; I know you just mentioned this, but I wanted to take a slightly different approach. As you think about the decision process and of course, you still have to see the label ultimately, but wanted to get your take on how you view pricing and that decision in the context of the value proposition in general but specifically in the context of being a non-immunosuppressant agent, and then I have a follow-up.

Eric Dube, CEO

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

Peter Heerma, Chief Commercial Officer

The last aspect of your question is important. We see the most excitement from the prescriber community as this allows for more effective treatment of those patients. Referring to the interim data we shared, a 50% versus 15% increase, that is a substantial increase in efficacy. It allows physicians to use sparsentan without going into the steroid path, where the reluctance is quite high for both patients and physicians. This is why physicians are excited about this mode of action, especially in the light of the KDIGO guidelines that I mentioned earlier, where there's a higher reluctance and caution regarding steroid use. Hence, we want to price to ensure broad access, positioning sparsentan as a new standard of care. The value proposition we are building is vital here.

Eric Dube, CEO

Yes. I think that's a great response, Peter. Thanks for that insight. And I think that's an important part as we consider our broader planning. Again, thank you all for joining us today. This concludes our first-quarter update. We look forward to keeping you updated throughout the year and speaking with you again soon. Have a great rest of your evening.

Chris Cline, Senior Vice President of Investor Relations

Thank you. And that does conclude today's conference. We thank you for your participation. Have an excellent day.