Travere Therapeutics Inc (TVTX) 2022 Q1 法說會逐字稿

Good day, and welcome to the Travere Therapeutics Conference Call. Today's conference is being recorded.

At this time, I'd like to turn the conference over to the Senior Vice President of Investor Relations, Chris Cline. Please go ahead, sir.

Great. Thank you, Justin. 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 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 Factors section of our Form 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?

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 time line 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. Consistent with our prior guidance, we will be providing an update following our regulatory interactions, but we will not be providing incremental updates before them. As a reminder, we believe the potential outcomes that are either the FDA is supportive of a submission of 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 am 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 performance for the quarter 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 bile acid 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?

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 the 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 we believe it has the ability to become foundational therapy for the future.

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 the review time line later this month. If priority review is granted, we would expect the 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 of sparsentan 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 am pleased that both DUPLEX and PROTECT, 2 of the largest studies to date in 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 5 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 pegtibatnase 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 ad board held in conjunction at SIMD, we received uniformly positive feedback on pegtabatinase's potential in HCU and invaluable insights to incorporate into our pivotal program planning.

Patients from the first 5 cohorts in the COMPOSE study are continuing in the open-label extension, and we're continuing enrollment activities in the 6 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?

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 initiate 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, but 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 teams execution with Cholbam. While we often see an even quality 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 engagement.

We continue to expect modest growth on 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 3 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 of sparsentan is approved. I continue to be very pleased with our progress. For example, we have already hired senior leadership with -- senior sales leadership with extensive rare and nephrology experience, and we have incredibly strong demand 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 the new treatment standard in rare nephrology if approved.

I will now turn the call over to Laura for the financial update. Laura?

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 growth 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 advancement 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 head count 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 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 effected in March. Taking 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?

Thank you, Laura. Last month, we announced that after spending more than 30 years in the biopharmaceutical industry and more than 7 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 to 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. And 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. And 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?

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

(Operator Instructions) And our first question today comes from Joseph Schwartz with SVB Securities.

This is Will on for Joe. 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?

Will, 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.

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 are confirmed IgA nephropathy diagnosis through a biopsy and that have consistent high protenuria levels. And 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.

Great. 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 in IgA nephropathy. So just wondering kind of how you're thinking about the competitive landscape moving forward with potentially multiple players in this market.

Sure. I'll ask Jula to give her perspective on that. And 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?

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 and patients remain at very high risk with the current treatment options we have, which is ACE inhibitors or ARBs. And so we believe sparsentan therapy with the significant reduction in proteinuria that we saw with PROTECT with a 50% reduction in proteinuria that sparsentan will become foundational therapy if it's approved. And yes, there are a number of other therapies in development that we believe sparsentan will be foundational therapy and some of the other niche therapies can potentially be additive to that.

Excellent and congrats on the progress.

And our next question will come from Carter Gould with Barclays.

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 EFR data from PROTECT anytime soon, are there plans to share or publish the data that you've shown already and maybe additional secondary analyses 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 the next go-round in terms of conversations?

Yes, Carter, thanks for the question. I think 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. And any additional data beyond the interim analysis on proteinuria which was the primary endpoint at that point could potentially increase the risk of unblinding (inaudible). And I think as we've discussed repeatedly in the past, that's really an area of focus for 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.

And as such, we do not have plans to publish any additional data at this point and also 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. So at this point, we do not have plans for additional analysis or disclosure of additional data beyond what we have to date.

Our next question will come from Greg Harrison with Bank of America.

This is [Mary Kate] on for Greg. Maybe just a question in regards to the potential sparsentan launch in IgAN. If approved, what are your expectations for the cadence on the initial uptake and ramp-up of sparsentan IgAN and maybe what are your expectations regarding reimbursement?

Thanks for the questions. And 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. And 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 that his team is working on this.

Yes. Very good. Thank you, [Mary Kate]. So it's too early indeed to give specifics how we see a large update. But I think what we are seeing very consistently in our own research as well as -- syndicated research as well as actually external research that is being done also among the investor community. We see a very consistent trend that physicians feel very excited about the opportunity, the mechanistic mode of action of sparsentan to claim that foundational therapy because to Jula's earlier point, like a lot of those patients remain not treated to the targets that physicians would like to see. So with (inaudible) often failing, we think that, that's really the position that sparsentan can claim. Also thinking about like the new guidelines that was presented last fall.

With regards to your other question with access, we so far are very pleased with the interactions we've had with payers and the response we're getting from payers as well. They see the unmet need, they recognize the unmet need, and there is also a high interest with regards to new modalities and innovative treatments. So I think we're making good progress. I think 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 we're getting from physicians as well as from the payer community.

Yes. I think that's right, Peter. And [Mary Kate], the only thing that I would add to what Peter mentioned 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, and 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.

And our next question comes from Liisa Bayko with Evercore ISI.

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

So I think what our focus is to make sure that we understand the position of the FDA and what our time lines would be for an FSGS submission before we change any of the plans that we have in place. Nothing has changed in our plans to date, and 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 with -- before anything that may affect. But at this point, we don't see any of that. We've not yet met with FDA and our plans have not changed in our time line for MAA.

And if I can add one more question. Can you give some color on your collaboration with PharmaKrysto, like what is your rationale and how does that fit into your portfolio?

Sure. Well, we're really pleased about this opportunity. It is early, and it is an asset or a program that we believe is well suited within our rare nephrology expertise. This is an asset that -- or potential asset that is pre-IND. And so we're not discussing much at this point, but it is something that over the next couple of years, we do see that we have the potential for an IND and continuing to progress for development. We'll 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.

And our next question comes from Maury Raycroft with Jefferies.

Congrats on the progress. You disclosed some patient baseline characteristics from the IgAN PROTECT study in ERA conference abstract. Just wondering if you can help contextualize what's disclosed in the abstract. And maybe talk about what 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?

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

Sure. So 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. And what we think is really important is that both studies are representative of the planned patient populations. And so, we are excited to share this data with the nephrology community. And each of the populations are unique, and so you can see that represented when you look through the abstracts and that we cover those patient populations representatively.

I'll take the second question. Thanks for the question, Maury. I think the heart of it is compare and contrast sparsentan versus budesonide. And I think the -- and the potential impacts on that eventual labeling. Of course, it's speculation at this point. But 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 than 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. So 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. So we'll need to wait and see based on the review. But again, it's really going to come down to benefit risk, and I'm very confident in the position that sparsentan has in that arena.

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

It's very difficult to say at this point.

Okay. Okay. Maybe last quick question. Just 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 potential for an ADCOM so far?

Sure. Bill, would you like to take that?

Certainly. We don't expect to have an advisory committee. We asked the question during our pre-NDA meetings, and we ask them directly their answer was no. With what we know now, we don't anticipate having an advisory committee that could certainly change. And 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 ADCOM. So we're confident in their first answer that no, they don't intend to have one.

And moving on to Tim Lugo with William Blair.

Congratulations to [Laura Clague], as well as Chris on a 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 II meeting? Or do you need to complete the sixth cohort before your next FDA interaction? And can you also remind us how the formulation of the sixth cohort is different than the formulation used in the other 5?

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

Certainly. With the challenges that we're seeing in the manufacturing space, I think they're not so much specific to pegtibatinase, but I think that they're endemic within all of biologics manufacturer. You have a combination of a flexing the supply chain to manage a lot of COVID vaccine manufacturer around the world, and that was inserted into an already full contract manufacturing space. So that did 2 things. It took up manufacturing slots and made them more challenging to obtain. And it consumed a lot of raw materials and consumables. So those have been the areas where we've had challenges, and we're happy with the progress that we've made working through those. We continue to make progress on the manufacturing side, but it's important for us to let stakeholders know that it's that these are challenges that we've been navigating.

So on the second path of your question was the formulation difference for cohort 6. This is the first cohort that will be using the lyophilized formulation. Recall that cohorts 1 through 5 used a liquid formulation that, for stability reasons, was frozen at very low temperatures. So by going to the lyophilized formulation, it makes the overall handling of the material shipments and the supply of clinical trial material, much easier both on us as the sponsor and on our collaborators, but also on the patients and the study sites.

The only thing that I would add, Tim, just on that question of supply challenges, and these are not new. These are ones that we've shared in the past. And I think it's one that Bill's team is making great progress on, and we don't believe has any bearing yet on the timing of our interactions with FDA. We've made good progress with those interactions. We expect that they would continue to be. And again, Bill and his team are working through all of those challenges at good pace.

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

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. Certainly, there is a lot of weakness within the marketplace. We know that there are companies that may have either the lack of expertise and capability or cash to move their assets in rare disease forward. That said, we also want to be very mindful about our use of cash and be very sensitive to any potential dilution, particularly before we get sparsentan out there and have a successful launch there. So we -- our #1 goal remains the successful launch of sparsentan. We're doing all we need to, 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 want to add?

No, I think you covered it well, Eric. (technical difficulty) our position on cash, as we've mentioned on the call, we do believe our cash (technical difficulty) into 2024. Of course, to your point, that really is completing any additional BD work, but to Eric's point, (technical difficulty) seem to be a little more undervalued these days. So you never know, there could be a good fit out there, but nothing planned right at this point.

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

And our next question comes from Michelle Gilson with Canaccord Genuity.

This is Michael on for Michelle. Congrats on the quarter. Just a couple of more questions on pegtibatinase. So what is the path forward with pegtibatinase? How is your engagement with regulators been regarding moving forward based on a biomarker versus perhaps clinical outcomes? And what would you need to show in any secondary functional endpoints?

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

Certainly. Thanks for the questions, Michael. 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, et cetera. And 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 use of a biomarker as a clinical endpoint, and we're working with the agency and following their guidance on how to qualify total homocysteine as the appropriate endpoint for that, and those efforts are underway. I think if you wanted to use a clinical endpoint in this disease space, it would be very challenging because of the time scale on which these changes take place are longer than what traditional pivotal clinical trials are. There's just a mismatch in the duration of what would be required. So it really is an ideal setting. And there is precedent early from the '90s, but there is precedent of a drug that was approved using total homocysteine as a biomarker. So we're optimistic that we'll be able to achieve that once we've completed those interactions.

Jula, do you want to take the question around clinical secondary endpoints?

Yes. As (technical difficulty) disease as Bill mentioned, (technical difficulty). As Bill mentioned, the disease is very slowly progressive and some of those secondary endpoints we would be collecting as patients would be in our studies, but they develop over many years in time. So those clinical endpoints such as ocular effects or thrombotic events would be collected over many, many years and not as part of homocysteine direct lowering over a short term. And of course, for the patients, from their perspective, eventually their goal would be able to liberalize their diet. And so, that would be the ultimate goal over the long term, and we hope to be able to capture some of that information eventually over time.

And just one quick one more on pegtibatinase. How is the -- how does the IT look or how long do you anticipate an exclusivity period?

Yes. So we do have a patent family for pegtibatinase, but I think that 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.

And our next question will come from Laura Chico with Wedbush Securities.

I just have 2. So 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 of proteinuria. So I'm just wondering kind of 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?

And then my follow-up question is actually perhaps for Jula or Eric. You made the comment earlier about sparsentan serving as a foundational component versus other MOAs in development for IgAN. And I'm curious if you could perhaps elaborate a little bit more in terms of what specific features make sparsentan well suited to be a foundational treatment?

Certainly. I'll take that first on FPRE. I'll ask Jula to add anything further because her work before joining the company certainly involved a lot of the foundational work tying robust measures of proteinuria to long-term renal outcomes. But that really is the foundational element of FPRE. It is a robust measure of proteinuria reduction and is in -- using some of the largest registries of FSGS patients correlated with longer-term renal survival and eGFR. And so, 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 I think fundamentally, it's the same focus of measuring proteinuria, which is aligned with how nephrologists think about treating these patients as well as eGFR over the long term, which we know is very important to regulators.

Jula, anything else that you want to add on FPRE and then also the kind of profile of sparsentan making it a foundational therapy?

Yes. FPRE is more aligned with how we think of FSGS, which is a disease in which you're looking at remission. You can -- and it is a measure of proteinuria and patients getting to a certain threshold and a magnitude of reduction, so it captures that. And as Eric said, it is the measure which has the strongest correlation with protecting eGFR and preserving kidney function and delaying time to dialysis or transplantation. So it has the greatest correlation there.

However, it's ultimately a measure of reduction of proteinuria. So it is consistent with the other trial. And so we just have the greatest data for that endpoint.

Let me answer then a little bit further about why we believe sparsentan can be foundational therapy. So sparsentan itself blocks endothelin and angiotensin receptor in a single molecule. And so the benefit of that is you reduce proteinuria, and you are getting a combined mechanism in a single molecule. And so you get the safety profile with that in addition to the magnitude of the proteinuria reduction.

And so essentially, you can switch patients from their therapy of an angiotensin receptor blocker or an ACE inhibitor over to a safe and effective therapy with a significant reduction in proteinuria, which we know we've demonstrated is beneficial on reducing proteinuria. And so that's why we believe it can be foundational therapy. So far, it's safe and it's effective.

And Peter, anything you'd want to add? Yes.

Yes. No, I think Jula, I think it's a great explanation. What we also hear from our physicians is that they are very comfortable with the mechanistic approach because it allows itself for add-on therapies in need. And I think that's what gives confidence to the decisions we are speaking with that they see this like frontline treatment early in the treatment paradigm, allowing for additional modalities if needed to add.

Congrats to Chris and Laura both on the transition.

Moving on to Do Kim with Piper Sandler.

This is [Skyler] on for Do Kim. 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, the indications for FSGS could be 2x the dose of IgAN? I'm curious if you could provide any color around your thoughts around that.

Sure. Thank you, [Skyler], for the question. So I'd say largely, it's early for us to talk specifics around pricing. That said, there's a lot of work that we're doing to assess the burden of illness and the health economic aspects of sparsentan. And our overall strategy for the pricing and reimbursement approach of sparsentan is to ensure broad access within the label population to make sure that patients are able to benefit from sparsentan. But ultimately, that's the way that we will be able to achieve our vision of sparsentan being a foundational therapy. I'll ask Peter to talk a little bit more about how his team is thinking about the potential price difference given the difference in dosing.

Well, I think it's well said, Eric, I think you covered the majority there. I think it's a different disease, states and also FSGS is generally seen as a more progressive disease. Your point is well taken (inaudible) if you have to take into account from a pricing perspective, but there's also like the building of disease to Eric's point is different as well. And all those aspects, we take into consideration before we make a pricing decision. Our initial launch will be in IgAN, and I think we have a comparator there already. So I think that allows you some flexibility, with more to come on that based on the data that we are gathering right now.

And our next question will come from Ed Arce with H.C. Wainwright & Co.

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 I 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.

Okay. Great. Thank you, Ed, for the question. Peter, would you like to take that?

Yes. I think the last aspect of your question, I think, is the important part, right? And I think that's where we see most excitement from the prescriber community because this allows them to more effectively treat all those patients. And again, referring to the interim data that we have shown 50% versus 15% is a substantial increase of efficacy. And it allows physicians to use sparsentan without going in steroid path and do lock in for the steroids is quite high, both in patients as well as with physicians. And I think that's why physicians are so excited about this mode of action.

Also in the light of the KDIGO guidelines that I was mentioning earlier, where that you see a higher reluctance and caution with regards to steroid use. So to Inrig's earlier point, we want a price for broad access because we think this product has the potential to become a new standard of care. The value proposition that we are building, and you have to take into consideration that kidney disease patients, in particular, those patients have progressed to a dialysis are amongst the most expensive patients for payers and society. And so I think we have, especially for the rapid progressing patients, we have a strong glomerular disease that we can build upon.

Right. Great. And then thinking through the expense structure for the rest of the year and your expectations there, I wanted to get -- excuse me, your take on the commercial readiness activities that are ongoing, not only now and through presumably November when you have a PDUFA date, but also what you may be leaving pending approval.

Yes. Great question, Ed. I think first, let me say that our approach is to plan for success in our launch overall and to be ready for day 1 of approval. And that's largely what is driving a lot of the work that Peter and Jula's team are doing in launch readiness. So there will be, as Laura mentioned, a continued increase in our SG&A throughout the year, not just in the expansion of our commercial infrastructure, but also in investing for that launch from day 1.

We recognize that, that may be different from other companies where you wait until kind of you've derisked a lot of that. We are planning for success, and I think we'll continue to provide updates on what that looks like and how we're preparing for launch later this year.

Peter, or Laura, anything else that you want to add?

No, I think you covered it well, Eric. I think we are building upon an organization that is existing that has shown year-over-year that they are successful in identifying and treating patients. I think to the point that you're making, like how does that expense look like? I think we are really focusing on 3 aspects. One is educating the market, in particular, making sure that physicians are comfortable with that new mechanistic approach of dual angiotensin and endothelin antagonism. 2, make sure that we educate the payers and they understand the building of disease and IgAN and FSGS. So our value proposition is well received.

And the third one is increasing the awareness of sparsentan also the intention to treat. And also on those parameters, we see nice progress both for our end reserves as well as external reserves.

That does conclude the question-and-answer session. I'll now turn the conference back over to you for any additional or closing remarks.

Thank you, Justin, and 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.

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