Good day and welcome to the Travere Therapeutics Fourth Quarter and Full Year 2023 Financial Results and Corporate Update Conference Call. Today's conference is being recorded. At this time, I would like to turn the conference call over to Anne Crotteau. Please go ahead, ma'am..

Thanks, Jenny. Good afternoon and welcome to Travere Therapeutics fourth quarter and full year 2023 financial results and corporate update call. Thank you all for joining. Today's call will be led by our President and Chief Executive Officer, Dr. Eric Dube. Eric will be joined in the prepared remarks by Dr.

Jula 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 up for the Q&A session.

Before we begin, I'd like to remind everyone that statements made during this call regarding matters that are not historical facts are forward-looking statements within the Safe Harbor provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements are not guarantees of performance.

They involve known and unknown risks, uncertainties and assumptions that may cause actual results, performance and achievements to differ materially from those expressed or implied by the statement.

Please see the forward-looking statement disclaimer on the company's press release issued earlier today as well as the Risk Factors section in our 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, February 15, 2024 and Travere specifically disclaims any obligation to update such statements to reflect future information, events or circumstances. With that, let me now turn the call over to Eric.

Eric?.

Thank you, Anne and welcome, everyone. 2023 was a year of many great achievements for Travere as we work towards our goal of breaking down barriers and treating rare diseases with historically little innovation.

At the start of 2023, we gained the first approval from our pipeline, delivering sparsentan or FILSPARI, as the first and only non-immunosuppressive treatment option for people living with IgA nephropathy or IgAN.

For decades, people living with IgAN, most of whom are diagnosed in their 20s and 30s and on average face kidney failure in 10 years had limited treatment options.

We are proud to help lead the growing evolution of the treatment paradigm that we believe will ultimately see patients get diagnosed and initiate treatment earlier and where physicians will ultimately utilize FILSPARI as a foundational treatment with its superior proteinuria reduction and accrual of kidney preservation benefit.

Following the grant of accelerated approval, our team quickly initiated our comprehensive commercial launch plan and worked throughout the year to lay a strong foundation for FILSPARI uptake. I am very pleased with our results. We continue to make substantial progress in physician demand, payer coverage and revenue, the key aspects of the launch.

Of note, FILSPARI is the only recent launch in the rare kidney space that has seen consistent growth in demand each quarter in its first year and we saw a meaningful inflection in net product sales to close out 2023. Last year, we encountered a challenge in our pursuit of a better outlook for the FSGS community.

Specifically, the DUPLEX study of sparsentan in FSGS did not achieve the results we had hoped. And following our FDA engagement, it was clear we would not be in a position to submit an sNDA at that time based on the DUPLEX results alone. I am incredibly grateful and proud of how our colleagues at Travere learn and quickly adjusted.

We moved quickly to align our investment in this program, implement a strategic restructuring of our organization to focus our resources and concentrate our efforts to collaborate with regulators with the goal of identifying a potential regulatory path forward in the future.

As for pegtibatinase development program for classical homocystinuria, or HCU, we achieved important milestones in 2023. Globally, we believe there are 7,000 to 10,000 patients diagnosed with HCU who are not in full control of their homocystine levels.

With better diagnosis and a future where an effective treatment is available, we believe this may grow by 50% or more over time. Last year, we generated additional exciting data from our Phase I/II COMPOSE study which further demonstrates the potential for pegtibatinase to become the only disease-modifying therapy for HCU.

With these data, we worked closely with regulators to align on a Phase III program, utilizing total homocysteine reduction as a primary endpoint and initiated that study before year-end. All of our efforts last year positioned us to start 2024 with focus and a plan for execution across the board.

Strong launch performance in FILSPARI remains our top priority for 2024 and we expect the momentum in our launch from the second half of 2023 will continue into the New Year. We are also executing on three additional priorities aimed at broadening access to FILSPARI.

Of note, we are on track to submit our sNDA this quarter to support conversion at FILSPARI from accelerated approval to full approval for IgAN in the U.S., together with our partner, CSL Vifor, we expect an opinion on conditional approval of FILSPARI in Europe from CHMP later this quarter. We're optimistic that this will be positive.

And with our recent agreement with Renalys, we are looking forward to aiding their development plans to ultimately enable access to FILSPARI in Japan and other regions in Asia, where IgAN is an even more prevalent disease and leading cause of kidney failure.

And importantly, we are excited about the opportunity we have with pegtibatinase, our novel investigational enzyme replacement therapy being evaluated for the treatment of classical homocystinuria, or HCU.

In 2024, our focus will be on enrolling our Phase III HARMONY trial and raising awareness of the need for innovative treatments for this rare disorder. Let me now turn the call over to Jula for a clinical update.

Jula?.

Thank you, Eric and good afternoon. I'm very pleased with the progress made on our clinical and medical affairs initiatives in 2023. With our achievements last year, we are well positioned to ultimately deliver two new treatment standards in rare diseases with limited options available.

As for FILSPARI, we completed the 2-year double-blind dosing periods for our studies in FSGS and IgAN. It's important to highlight that our studies are the only ones in the space that use a maximally optimized active comparator, setting the bar highest in the field.

The results which clearly demonstrated robust proteinuria reduction and preservation of kidney function in IgAN were simultaneously presented as late-breaker presentations at ASN and published in world-renowned medical journal, the Lancet and New England Journal of Medicine.

Following those data presentations, we have received positive feedback from nephrologists about the foundational role that FILSPARI can play in long-term kidney function preservation for patients with IgA nephropathy.

What is resonated with nephrologists is that FILSPARI is the only approved non-immunosuppressive treatment for IgAN and it's the only molecule that works by simultaneously blocking the 2 key pathogenic pathways in the kidney. Endothelin-I and angiotensin II, that both work together to drive damage and kidney function loss.

FILSPARI dual mechanism of action is critical to inhibiting the damaging pathways in the kidney in order to achieve sustained proteinuria reduction and long-term kidney function preservation that accrues over time.

Unlike intermittent therapies which may have short-term benefits on kidney function, FILSPARI demonstrated a long-term accrual of benefit on eGFR. In the PROTECT study at 1 year, there was a 1.7 mill per minute favorable effect on absolute eGFR with FILSPARI compared to maximize titrate irbesartan.

And that benefit increased to 3.7 mill per minute greater eGFR at 2 years. Importantly, the rate of loss of kidney function in year 2 compared to year 1 was significantly slower for FILSPARI-treated patients, suggesting a potential additive benefit with longer-term treatment.

This year-over-year accrual of benefit is important for a patient who has ongoing kidney injury over their lifetime and may otherwise be facing kidney failure less than 10 years from diagnosis.

Our 2-year data from the PROTECT Study in IgAN shows that FILSPARI is superior to historical RAS inhibitors and is safe for chronic use which is critical in treating patients for life.

Community and academic nephrologists are continuously highlighting to us the early clinical experience with FILSPARI, where they see significant reductions in proteinuria and the ability to safely use FILSPARI with their patients chronically.

We believe this cements the role that FILSPARI can play by replacing RAS inhibitors as foundational care for those at risk of rapid disease progression due to uncontrolled proteinuria.

Following the positive results from PROTECT, we successfully completed a pre-NDA meeting with FDA to discuss our plans to submit an sNDA to convert FILSPARI from accelerated approval to full approval for IgAN. Importantly, we aligned with the FDA on the data analysis to support our submission and to support potential broader labeling.

I'm pleased to report that we remain on track to submit the sNDA this quarter. We are at an exciting juncture in the evolution of the IgAN treatment paradigm. We believe that nephrologists are focused on treating the damage in the kidney and then preventing further damage systemically.

Our goal is to ultimately have FILSPARI used as the foundational care in IgAN essentially replacing the historical role of RAS inhibitors and then other medicines can be added as needed. As this evolution continues, there are a number of factors that we expect will help FILSPARI achieve this goal.

With a full approval from FDA, we would expect a broader label that reflects the full study population and the results. This would provide nephrologists and patients with greater flexibility to choose FILSPARI when seeking treatment options that can provide long-term kidney function preservation.

Additionally, we believe FILSPARI likely inclusion in the soon to be released KDIGO guidelines should further standardize use of FILSPARI with a nephrology community and potentially result in earlier treatment.

As positions in up-to-date and recent peer-reviewed IgAN treatment articles, we anticipate FILSPARI will be described as a foundational treatment in the KDIGO guidelines.

We also believe that the proteinuria target for treating IgAN overall will be lowered which would support earlier diagnosis, more aggressive treatment to avoid long-term damage as well as combination treatment in the future.

Furthermore, later this year, we expect to generate longer-term data from our ongoing [indiscernible] and SPARTAN studies which are designed to show FILSPARI can be safely used in combination with other medicines, such as SGLT2 inhibitors and that patients may benefit from earlier use of FILSPARI.

Such data will further support the progress towards FILSPARI achieving foundational care. Beyond the U.S., we have continued to work closely with our partners at CSL Vifor on the conditional marketing authorization application that is currently under evaluation in the U.S. EU.

Following a procedural clock stop to review the 2-year data, we believe that we are well positioned for a positive CHMP opinion this quarter and an approval decision next quarter.

Beyond the CSL Vifor territories, our recent agreement with Renalys provides FILSPARI with a regulatory pathway that has the potential to deliver FILSPARI across a number of Asian countries in the coming years.

Overall, we are very pleased with the important groundwork laid in 2023 and we see a clear road map for increased utilization of FILSPARI for IgAN in 2024 and beyond.

Turning briefly to FSGS; with no approved therapies for tens of thousands of patients with this condition and the high rate of progression to kidney failure; we are committed to trying to find a path forward for sparsentan and FSGS.

We are taking a measured approach to evaluating our data sets and working with the community to reengage the FDA later this year towards the goal of ultimately being able to submit to have an FSGS indication added to the FILSPARI label. We anticipate being able to provide an update on this work late in the year.

As Eric highlighted earlier, our enthusiasm and pegtibatinase continues to grow. We were pleased to achieve alignment with regulators on the design of our Phase III program and to reach our goal of initiating the Phase III HARMONY study before year-end.

This study employs an innovative design with measurements very similar to our highly successful Phase I/II study which we believe provides a high probability of success as a registration-enabling study.

The Phase III HARMONY study is designed to recruit up to 70 patients with HCU and evaluate change in total homocysteine from baseline to week 6 to 12 as the primary endpoint. This is the measurement for which we saw a 67% reduction in the highest dose cohort in the COMPOSE study.

Patients will be followed in the double-blind period for 24 weeks in total to establish durability of effect and a robust safety database. Masimo's [ph] consistency there is a 10-week screening and diet stabilization period prior to randomization in HARMONY.

And patients who complete the full double-blind period will be eligible to enroll into an open-label study called ENSEMBLE [ph], where there is a protocolized diet liberalization substudy for eligible patients who have well-controlled total homocystine.

This portion of the study is designed to generate data throughout the life of the program and we believe it will ultimately be able to help patients understand how they may be able to increase protein intake by taking pegtibatinase, a key area of need for patients living with HCU.

As we move through 2024, we will be focused on ramping up enrollment in the HARMONY study and scaling our pegtibatinase manufacturing activities to support the full program and future commercialization. We look forward to top line data in 2026 with a potential approval in 2027. I'll now turn the call over to Peter for the commercial update.

Peter?.

Thank you, Jula. Looking back on 2023, we made robust progress on what we have outlined during our launch call in February last year.

[Indiscernible] as the future foundational care for patients at risk of rapid progression through educating our nephrology targets, securing broad access and ensuring a positive initial FILSPARI experience for patients and physicians.

And I'm really proud on the progress our commercial team has made in the past year, especially while adapting to the initial promotional restrictions that come with accelerated approval and an unexpected advance program for liver monitoring.

By the end of 2023, we reached 5,700 nephrologists with our sales team in regular face-to-face educational interactions that is 95% of our target base of 6,000 nephrologists that we believe treat about 85% of the addressable IgAN patients in the U.S.

These efforts resulted in strong and steadily increasing demand with increasing breadth and depths of prescribing nephrologists. In particular, in the fourth quarter, we built strong momentum for FILSPARI demand and I couldn't be more pleased with how we ended the year.

It was encouraging to see further growth in new patient start forms or PSFs after ASN Kidney Week, where the confirmatory PROTECT study results were presented and published. Importantly, we also received further validation of the FILSPARI profile from [indiscernible] leaders which was evidenced by an increase in key opinion leader prescribers.

We ended the fourth quarter with 459 new PSFs which demonstrated quarter-over-quarter growth for each period in 2023. In fact, this is the first recent rare nephrology product that has shown a continuation of growth in demand during each period of the first -- in the first year of launch.

In total, we received more than 1,450 patient start forms in 2023 which clearly indicates FILSPARI is helping fill a significant need for the nephrology community. On the payer front, we established a strong base allowing broad patient access. By the end of the year, coverage reached about 70% of U.S. lives.

In the fourth quarter, we added about 180 new FILSPARI specific formularies. And overall, more than 1,000 formularies have included FILSPARI with authorization criteria that are generally consistent to the FILSPARI label.

And if we account for plans that didn't yet include FILSPARI, would have a clear pathway for [indiscernible], that total is about 89% of the U.S. lives. Following our team's quick adjustments to improve patient education and provide further support for the liver monitoring REMS in the second half of the year.

We saw continued progress in our lead measures of REMS certifications in the first 14 days after receiving patient start form. This also led to a growing number of reimbursed patients initiating therapy during the quarter.

And we are hearing almost on a daily base on patients and physicians how impressed they are with the results that they achieved with FILSPARI. These results are consistent to what was observed in the PROTECT trial with rapid and sustained proteinuria reductions versus safety profile similar to ACE inhibitors and ARBs.

This is encouraging for patients that started using FILSPARI and likely why we are seeing high compliance rates so far in the loans [ph]. All these accomplishments resulted in a significant increase in net FILSPARI sales.

In the fourth quarter, we reported approximately $15 million in net product sales which resulted in nearly $30 million for the year. [Indiscernible] also remained steady, contributing approximately $25 million in net product sales in the fourth quarter.

We recently learned of an approval of a generic trial that we see was a narrower labeled and we will continue to monitor what impact that may have throughout the year. Overall, we ended 2023 with solid execution and this provides us with a robust foundation for strong performance in 2024.

In fact, in the first 6 weeks of the New Year, I'm pleased to see our strong FILSPARI performance continue. Our team is ready to show the true potential of FILSPARI in this New Year and we have multiple inflection points throughout 2024 that provides confidence in continuing growth.

Let me highlight the four areas that I am particularly excited about in the coming year. First, if we achieve full approval as targeted for later this year, we anticipate that an updated and potentially broader label will provide greater support for physicians to prescribe FILSPARI to more of their patients.

Second, as Jula mentioned earlier, we anticipate that FILSPARI will be included in the global KDIGO guidelines, scheduled to be updated this year. This will potentially provide uniform guidance for physicians to choose FILSPARI as an early treatment for their patients.

Third, additionally, if the guideline revision emphasizes earlier intervention by lowering the proteinuria targets, it would likely amplify the urgency to diagnose and treat patients earlier.

We believe this would increase the number of patients that would be eligible for FILSPARI and importantly, a broader label together with a potentially lower target to treat earlier in the guidelines, would allow us to establish FILSPARI as a foundational treatment in a larger addressable patient population.

And fourth, we expect the additional clinical evidence Jula highlighted earlier will ultimately provide additional support for physicians to treat earlier with FILSPARI and use it in combination with other available medicines for patients that may need more aggressive treatments.

With all of this in mind, I could not be more excited about FILSPARI's prospects in this New Year and we feel strongly that we are well positioned for significant growth in 2024. Let me now turn the call over to Chris for the financial update.

Chris?.

Thank you, Peter and good afternoon, everyone. Following our fourth quarter results, we are in a strong financial position. From an operational perspective, we continue to grow revenues and we have focused our investments on the ongoing launch of FILSPARI and IgA nephropathy and the advancement of our Phase III pegtibatinase program.

For the fourth quarter of 2023, net product sales were $39.9 million compared to $25.8 million for the same period in 2022. The increase is attributable to growth in net product sales from the ongoing launch of FILSPARI and IgA nephropathy.

During the quarter, we also recognized $5.1 million of license and collaboration revenue which results in $45.1 million in total revenue reported for the period compared to $29.3 million in the same period in 2022.

Research and development expenses for the fourth quarter of 2023 were $59.7 million compared to $58.1 million for the same period in 2022.

The difference is largely attributable to the continued advancement of our pegtibatinase clinical program, partially offset by reduced investment in our FILSPARI Phase III programs following the readouts from the 2-year endpoints.

On a non-GAAP adjusted basis, R&D expenses were $55.3 million for the fourth quarter of 2023 compared to $52 million for the same period in 2022. Selling, general and administrative expenses for the fourth quarter of 2023 were $63.6 million compared to $57.1 million for the same period in 2022.

The difference is largely attributable to the commercial launch-related activities following the accelerated approval of FILSPARI in February of 2023. On a non-GAAP adjusted basis, SG&A expenses were $49.7 million for the fourth quarter of 2023 compared to $44.3 million for the same period in 2022.

During the fourth quarter, we recognized $11.4 million in restructuring fees related to this strategic reorganization that was announced in December. Total charges related to the reorganization are expected to amount to between $12 million and $14 million.

Total other income net for the fourth quarter of 2023 was $5.7 million compared to $1.1 million in the same period in 2022. The difference is largely attributable to an increase in interest income during the period.

Net loss, including from discontinued operations for the fourth quarter of 2023 was $90.2 million or $1.18 per basic share compared to a net loss of $65.8 million or $1.03 per basic share for the same period in 2022.

On a non-GAAP adjusted basis, net loss, including from discontinued operations for the fourth quarter of 2023 was $71.8 million or $0.94 per basic share compared to a net loss of $46.9 million or $0.73 per basic share for the same period of 2022. As of December 31, 2023, the company cash, cash equivalents and marketable securities of $566.9 million.

Looking ahead, we expect meaningful growth in net product sales of FILSPARI in 2024 and we look to achieve non-GAAP operating expenses below $400 million for the year. We also anticipate meeting milestones for both FILSPARI and pegtibatinase that will result in us making expected net payments of approximately $50 million during the year.

With our strong balance sheet, expected growth in FILSPARI revenues and measured investments we currently expect that our cash balance can support operations into 2028. I'll now turn it back over to Eric for his closing comments.

Eric?.

the continued strong execution of our FILSPARI launch, the expected conditional approval of sparsentan in the EU and full approval of FILSPARI for IgAN in the U.S. with potential broader labeling, updated IgAN treatment guidelines and further data generation to reach the growing number of patients in need of a better therapy.

Finally, I'm particularly excited about the advancement of our development program for pegdibatenase as the only potential disease-modifying therapy in a market that is expected to grow meaningfully over time.

This year, we look forward to raising awareness of HCU and enrolling the Phase III HARMONY study with a goal of achieving top line data in 2026. Let me now turn the call over to Anne to open up the lines for Q&A.

Anne?.

Thank you, Eric. We can now open the line-up for Q&A. Jenny..

[Operator Instructions] We will now take the first question from the line of Joseph Schwartz from Leerink Partners..

I guess I'll ask on FILSPARI, how much does the higher hurdle that FILSPARI had in the PROTECT trial seem to resonate with the prescribing community. Do they appreciate that patients in the control arm were so well managed.

Does this impress them? Or do you have more education to do in order for them to appreciate FILSPARI's relative to performance and protect?.

Joe, thanks so much for the question. Peter, why don't I turn that over to you and perhaps you can also comment on what we saw coming out of ASN where there was much more discussion about the PROTECT trial and trial design..

Yes, I have to take that question, Joe. I would say the conversations I have had with physicians and I think that's also being in the line with the market results that we saw. But if we outline the study design of PROTECT and the understanding of like an active control arm is understood.

There's really like great appreciation for the -- for the very robust results that we have. And we have highlighted earlier in the call, like 1.7 mill per minute per year improvement. And then in the second year, it is actually 3.7 mill per minute per year. So an accumulation of benefit over time.

And I think that is something that the physicians if they understand design really speak highly of..

Jula, is there anything that you'd like to comment from your team's engagement with thought leaders on that trial design and the high bar?.

Yes. I think it does take some education because all the other trials are comparing to a not fully optimized standard which we know historically 50% and really all the other trials aren't [indiscernible] we have a higher hurdle.

And so when they initially see the comparison in the slopes, most of which they don't look at in their clinical practice, it takes some education to look at the benefit and then also the accrual of benefits that we can see.

We only did a 2-year snapshot but you know that if you have a benefit that's better in year 2 versus year 1, then that's going to continue to improve year-over-year. That does take some time but they get it once they spend some time with the data and the information..

And I think this is going to be a very important part of why we're eager to have full approval and a label that will allow us to talk about that long-term benefit and how the trial design really does help explain why we see such great results throughout the 2 years..

Our next question is going to come from Greg Harrison from Bank of America..

Just thinking through the IgAN treatment landscape.

And when it comes to comparing different treatment options, especially in light of recent data, is it fair to say that the focus for investors should be on the eGFR benefit? Or is there a better way to think about it?.

Greg, thanks so much for the question. I think the very short answer is no. But I'm going to let Jula talk a bit more about what she as a nephrologist and what she's hearing from thought leaders about the evolving treatment landscape and the importance of eGFR and proteinuria.

Jula?.

First, I'll start with proteinuria and eGFR, both matter for how we take care of patients but I'll highlight that proteinuria is really critical for nephrologists for patients and for regulators for evaluating and looking at risk as well as response to treatment over time.

As the proteinuria changes can occur more quickly versus the eGFR changes require many years to show effect. And I would say, importantly, multiple data sets show a strong correlation between proteinuria reductions over time and risk of kidney failure, that's why it's an approvable endpoint for accelerated approval.

And we also know that we need to get patients as close to normal as possible. When you look at the rate -- still remain at risk if they got 0.44 grams per day. So getting patients closer to normal with regards to proteinuria is very important [indiscernible] we saw 1 in 3 patients on FILSPARI and PROTECT, achieve complete remission of proteinuria.

And so far [indiscernible] both reductions in proteinuria and eGFR preservation that accrues overtime. So I think all those are important factors to take into consideration..

Our next question is going to come from Anupam Rama from JPMorgan..

And a little bit more of a kind of an acute question as we think about FILSPARI in the first quarter.

Any guidance about how we should be thinking about payer reauthorizations and any seasonality considerations in the quarter?.

Anupam, thanks for the question. Let me just first say that Peter's team has done a really great job starting the year strongly and we've seen good performance. Peter, why don't I turn it over to you to talk a bit more about what we expect to see in those dynamics for Q1, recognizing that we've not and will not be providing guidance.

But I think certainly, Peter can talk about some of those dynamics in more detail.

Peter?.

Yes, happy to Eric. Yes, as I mentioned earlier, I think the -- across the 3 core fundamentals of launching a product that we made really substantial progress and in particular like ASN, I think, really allowed for building that momentum we saw like an increase of prescriptions, in particular, from thought leaders.

But we also saw like a good progress in our -- getting patients on paid product. And I think across the fundamentals, we see that the continuation of progress in the first 6 weeks of this year as well.

I think to your more specific question, like what is the insurance reset and reauthorization criteria, we move for the gross to net in the first quarter. While this is the first year we launched FILSPARI, so that's going to be a new learning. So we don't know that yet.

But if I look at the fundamentals, I'm really pleased with the progress we have been making..

Our next question is going to come from Tyler Van Buren from TD Cowen..

So as part of the sNDA submission by the end of the first quarter for the full approval of FILSPARI and IgAN.

Does that include a request to have the black box and revs warning removed? And if so, can you describe to us how you supported that request?.

So thanks so much for the question, Tyler. Jula, why don't I first turn to you to talk about the data that we've seen from a safety standpoint. And then, Bill, certainly, you can add what we're thinking in terms of engagement with FDA during the sNDA process..

So I want to highlight that across our development program and first year commercial launch including patients who we've had in some of our trials on treatment for after 10 years, we have had several cases -- several cases [ph].

Now I do note that there isn't historic for press removal of [indiscernible] but we certainly are going to advocate for the best process for patients which may [indiscernible] comment further on our process..

Yes. With the -- the anniversary of the approval, we will be submitting our first annual REMS update which we'll highlight the data that we've collected around liver safety and we'll also be submitting the sNDA this quarter which will give the full 2-year data in the PROTECT study.

Both of those give us a launching point to begin the dialogue around the potential modification of the REMS program. At the end of the day, we need to start this dialogue.

We don't know what the FDA's response will be but it's really important for us to have the data that we have now and to begin the conversation and these interactions with the agency..

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

A lot of mentions of momentum and inflection on the call there. The new start form increase was somewhat more modest.

I guess I'm trying to understand is that sort of mid-single-digit increase in new start farms probably a fair characterization of what we should expect going forward until those inflection points that Peter mentioned sort of hit, it does seem like those are back-end weighted. Any color or commentary would be appreciated..

Carter, thanks so much for the question. I'd say that Peter can speak to some of the qualitative and directional approach that we expect to see throughout the year for both patient start forms and demand. We will not be providing guidance on those for the year but we certainly do expect to see a strong year of our performance, particularly in revenue.

But Peter, why don't you talk in a bit more detail about what we can expect to see moving forward..

Yes. Thanks, Carter, for the question. I think it's the characterization that you have to take it into context of a prescriber base that had very low innovation in the last 30 to 40 years. And so I think the adaptation, it takes time to educate the broad community and get to the prescriber base.

And within that context, I think the growth that we're showing in Q4 and basically in every quarter in the first year, I think what I called out earlier is that this is the first recent [indiscernible] where you see that continue growth. I think that is something that is the data we expect this year.

The guidelines to be updated that is a good momentum to show continuation of growth in patient start forms and more importantly, ultimately in revenue as well. So, I think I understand your question but I think you have to bring that into consideration with an audience that is maybe not used to that much innovation and really requires education.

And with the experience that they are gaining and that's what we are seeing right now is the best advocate for further use and further prescription. And that's where we are right now. So I think in the first year, the plans to have the continued growth that we saw, I'm really pleased with..

Our next caller is going to be Maury Raycroft from Jefferies..

For the EU, you initially had filed for conditional approval and it sounds like that's what you're expecting this quarter but then you submitted the 2-year data to the EU which led to the clock stop.

So is it possible that you could get full approval in the EU? I guess is there any possibility for that? Or will it still be conditional and has EMA provided any feedback after reviewing your 2-year data?.

Maury, thanks so much for the question. Bill, I will pass that over to you..

Sure. Well, we remain optimistic about the positive CHMP decision that will be made this first quarter. The 2-year data, I think, was helpful for the EMA in making their decision because it essentially removes the regulatory risk associated with their equivalent of accelerated approval.

There wasn't a discussion of potential full approval and there are aspects of the data package that they don't have yet. The full tables figures and listings weren't provided more of a top line look at the 2-year data. So I wouldn't expect a full approval with this round..

Got it.

And has EMA provided any feedback after seeing the 2-year data that they've seen?.

No. There wasn't an opportunity in the process for feedback from that at this point in time, I'm sure we'll have dialogue as we go towards full approval..

Our next person is going to be Tim Lugo from William Blair..

This is John [ph] on for Tim. So just wondering if you have any sense on if the agency might require an ADCOM to discuss conversion to full approval.

And as a follow-up, if you have any sense on the last date that you might be informed that ADCOM might be required?.

John, thanks for the questions, Bill. I'll pass that back to you..

Sure. I don't think that this is the type of regulatory decision where the agency would seek advice from an advisory committee. I think the data is quite clear. So there isn't a need to go out to additional external experts to help interpret trial results. And I think also there isn't a controversial aspect for this.

So I don't anticipate that the agency will panel an advisory committee. Certainly, if they do, we will be ready. Your -- the second part of your question was the timing. Generally, the agency will let sponsors know within 60 days of submission, whether or not they're going to have an ADCOM or not.

So if we submit in the first quarter by mid- to late second quarter, we will know whether or not we're going to be going for an ADCOM..

Our next question is going to come from Liisa Bayko from Evercore ISI..

Do you have any more color on when the new guidelines will be released?.

Jula?.

We know they're working on it now but I can't provide more color other than we were anticipating potentially this quarter and that means they would be finalized later in the year but we know it's in the works..

Okay. You mentioned compliance rates were good. And can you speak to kind of where you are with compliance? And also can you describe growth from that for the year? Like what kind of average for the year should you be thinking about or when would normalize? Any color there would be helpful..

Sure. Peter, I'll turn that over to you..

I'll take the question on the compliance and Chris, maybe you can take the gross to net earn. So on the compliance rate, like if you look at [indiscernible] for chronic disease without a [indiscernible] method disease, overall compliance rates are not very high. What we see with FILSPARI so far, it is actually really high.

It's higher than what we anticipated, especially when you also have a REMS program with monitoring that requires monthly liver testing. So far, we see very strong compliance rates. I think it keeps also to the experience patients are having. And that's for the first time, they actually see that be in control to the target levels.

And I think you have to take into consideration like a lot of those patients, they feel that they're losing. I mean, over the course of their disease, they hear every time from their physician that they're not yet on the target.

And I think now with FILSPARI, they feel like, hey, you know what, we are able to reach the target and I think that is motivating patients to continue to use the product and supply I think we see also high compliance rates..

And Liisa, just on the gross to nets, we've been pleased with how we've seen things meet our expectations of having a mid- to high teens gross to net. The other thing that I would say is for 1Q with the rest of the year, we may see that be a little bit higher as we have some of our other products in the past.

But overall for the year, we would expect it to remain in that mid- to high teens level..

Okay.

And then can you comment at all on like how many patients were on kind of exiting 2023 on FILSPARI?.

So we've not provided guidance for any KPIs on a number of treated patients. I think Peter can talk about directionally what we were seeing as we ended the year. But Liisa, we're going to continue to provide updates on PSFs on payer coverage and on revenue at this point in the launch.

Peter, you want to provide anything further to this question?.

I think that's right. As I mentioned earlier, I think we're making robust progress on all the fundamentals, including the pull-through getting patients on base product. I think the process is well within benchmarks which you would expect from rare disease products.

And so I think we will see that continuation and it will be reflected by revenue as well to Eric's point..

Our next question is going to come from Vamil Divan from Guggenheim..

Great. Maybe just a couple of follow-ups on the payer side. So I think, Peter, I think you mentioned your prepared remarks that the payers are -- they're sort of acting generally consistent with the label in terms of the patients that they're reimbursing therapy for.

I'm curious if maybe you can just give a little more detail there in terms of when they're deviating from the label sort of what issues, if any, are they sort of raising? And then the second question I have is more around the full approval, assuming you get that sort of later in this year, would you expect sort of a sort of immediate change in sort of payer behavior on that? Or is that something we'll have to wait until sort of the 2024 -- 2025 cycle starts up in terms of formulary status or authorizations..

All right. Peter, I'll hand those over to you..

Yes. With regards to authorization criteria. I mean there's always certain effects that the payer is expecting to see -- and so I think where we are is that especially in the beginning when we got the label and the label was kind of safe on patients with rapid progression of disease with regards to proteinuria states like generally 1.5.

When we are seeing that players in most of the authorization criteria refer to the label but also refer to the clinical guidelines and that has lower proteinuria targets. So that allows for a broader use.

And that's why to my earlier point in the call with a further lowering of the proteinuria targets within the legal lines [ph], a company is like a broad label fulfills powering that would allow them also for a broader patient population that is eligible for paid products..

And then, Peter, what is your comment on the question around full approval and how payers will respond with full approval and how quickly they might be able to review..

Yes. So I think it speaks a little bit to what I said with a further lowering of proteinuria target and then also a broader label, whether it's no restriction in proteinuria that authorization criteria on a threshold of proteinuria may disappear. And so that allows for a broader patient population. I think that's one aspect.

I think another aspect is -- and I think your question may have been referring to like the evolving competitive landscape as well with new competition coming in. I think the lead time that we have and the strong base that we have in formularies provides a very strong position, especially since we have like the highest standard for study design.

I mean this is the only study that has active comparator which is basically the gold standards how a payer is evaluating new products. So I think we are in a strong position with regards to lead time as well as study deciding how payers are evaluating that evolving landscape..

And our next question is going to come from Alex Thompson from Stifel..

I want to pivot a little bit to pay the bad news here.

Maybe could you talk a little bit about the HARMONY study through the expectations around enrolling 70 patients or at least up to 70 patients based on your experience with the Phase I/II, how well identified are these patients? If this is a 12-week primary endpoint of the top line is the 2026 readout conservative at this point? Or how are you thinking about that?.

Alex, thanks so much for the question and also for the focus on the pegtibatinase program. Jula, I'll turn that one over to you..

So thanks. We think this is an exciting trial design that focuses on changes in total home 15, not just at 6 to 12 weeks but also looking at durability of effect. So it is a 24-week study and then patients roll over to our open label which is able to look at diet liberalization.

And to your point, we are looking to recruit 70 patients from more sites than we did for COMPOSE. It's about 50 sites overall which will give us top line data in 2026. And while we have started the trial and we do have a list of patients who are excited to participate.

We are intentionally moderating our enrollment initially to ensure we have a good experience for the sites and patients and also proper training at some of these sites to -- some of which are research naive and then also to ensure our CMC scale up to support the full study as well as commercialization..

So I think perhaps if you can comment on the enrollment period before for screening that it helps explain why the time line may be a bit longer than what people would typically say for this type of trial..

Yes. So because it is a 6-month trial, plus we have a 10-week run-in period where patients get screened to make sure they qualify as well as standardize their diet and that's really to try and optimize our chance of success that patients have understand the trial that they need to keep their diet table which clearly is going to impact your endpoint.

We want to maximize our chance for success at the end. So it's a bit longer than what you first stated..

Yes. And we'll certainly look to move swiftly on this but we -- for all of the reasons that you've explained, we've been very thoughtful around the time lines that we've put out there.

Alex, the only other thing that I would mention that we -- that gives us confidence in the enrollment is that as we see increased awareness within this community, there are more and more patients that are being identified and we would absolutely expect that there will be a growth in the number of patients identified, diagnosed in the overall market growth.

So this is something that we believe will certainly be a tailwind for us with the HARMONY trial and even more so as we look to reach these patients once we have approval..

And I guess, how many patients do you feel like you need to enroll to feel confident in powering if it's not 70..

Bill, why don't you talk about the powering but I can say we absolutely are confident in finding these patients. I think we've been able to help in thinking through where these patients are, with sites, et cetera. So I think Jula's team has done a really great job of ensuring how we can enable success in the HARMONY trial.

And I think, Bill, you can talk about a high level of the powering..

Yes. No, certainly and I appreciate the question. We’re very confident in the powering of the study. And recall in Jula's initial remarks, she mentioned the 67% reduction in total homocystine that was observed in Phase II.

So with that level of efficacy, even with a significant diminution in the treatment effect or a reduction in the overall total sample size which we don't anticipate. We certainly are in a good place to still achieve the endpoint. So I'm confident that we'll get there..

Jenny, can we move to the next question, please?.

Yes, we have Mohit Bansal [ph].

Can you hear me?.

Just wanted to understand. I mean I know you don't provide the patient count. But if I look at the average number of patient forms, coming from second quarter to third quarter and then third quarter to fourth quarter, it seems like there's a 57% increase but then there's a substantial increase in revenue.

So is this because you are converting a lot more of those patient form into paid patients? Or is there a stocking in part involved here? Can you help us understand that? And then last -- second question is on the price increase, I think you took a price increase in January, should we expect some benefit in 2024 due to that price increase?.

Okay. Thanks so much for the question. Peter, I will turn that over to you..

Yes. So thanks Mohit for that question. So as I mentioned, like one of the core fundamentals is making sure that patient forms transition ultimately to patients on products and in particular bases on paid products or you continue to increase the revenue.

And I think what you saw in this quarter is that we made robust progress in particular, also in the pocket of patients that we described in the earlier quarter that required some additional handholding and education with regards to the REMS loss I think -- as I mentioned, like the patient REMS certification within the first 14 days has increased quite substantially and that allow patients to go through the process and get to base product more quickly.

So good progress there. To Eric's earlier point, we don't provide further details on how many patients we have on product. But I think that transition from patients to our form ultimately get paid product, we made significant progress.

On the second question with regards to price and price increase, indeed, we had a price increase in the beginning of the year. Now that we have the confirmatory data and you see that proteinuria reduction -- the robust proteinuria reduction provides longer-term eGFR and getting preservation as well.

So we thought it was justified to have a price increase for this year..

And maybe just one final thing, Mohit, for your question on inventory. That has been stable, so there has been no pattern of stocking. So I think Peter is absolutely right. We expected to see a greater inflection in revenue as our teams are able to help those patients through the process.

You would imagine that, that is going to continue that trend this year with faster growth in revenues than perhaps what we see in patient start forms but we'll certainly apprise you how we're doing at the end of Q1..

And our next question is going to come from [indiscernible] from Citi..

I had one on FSGS.

Just curious if there were any recent updates with regard to the work that I believe the FDA is doing in collaboration with you on defining some of the optimal endpoints for FSGS, whether there's some variations of the eGFR slope endpoint that may be more appropriate based on some of the data cuts that you're exploring? And then secondly, on the broader landscape in IgAN, just wondering, obviously, there's been a lot of visibility around some of the newer mechanisms, anti-B-cell mechanisms.

Wondering whether FILSPARI, given the position is the conditional therapy, may benefit from a combo study using the B-cell modulators on top of FILSPARI at a future point..

Great. Thank you for the questions. And Jula, I will turn those over to you..

So thanks. As far as FSGS, we are continuing to do our processes with our data and external data sets, putting our trial into historical context. With regards to the FDA, this is a partnership with [indiscernible] which is a patient organization with academics and the FDA. And it's called Parasol [ph].

There's a website it's public and it's really to redefine the endpoints. And what they've recently announced is they're really looking at alternative proteinuria-based endpoints to help enable the regulatory pathways for FSGS.

We plan to reengage the FDA following their final analysis and decision on what those endpoints should be under this Parasol Group [ph] and they're targeting ASN for that time line?. And then your second question is around some of the newer agents and how FILSPARI should be placed.

And I think it's really going to be an exciting few years for IgA nephropathy patients in some of these new therapies most of which target different parts of the injury cascade contributing to IgAN and hopefully, they'll become available outside the context of a clinical trial but we're a few years away from that.

But I would add that all additional immunomodulating agents are being used on top of standard of care foundational treatment. And that's where FILSPARI plays a foundational role because it targets the injury in the kidney and the response to the [indiscernible] deposition and protects against further damage.

And really, we're really aligned with the KOLs. You need to target 2 things ongoing damage in the kidney with foundational treatment. And to your point, you could potentially add another agent that targets upstream pathways but that's additive.

As far as other trials I think it's important to realize that every other trial is studying a new agent on top of standard of care and many of those trials now because of FILSPARI superiority over ACEs and ARBs they're being allowed as part of the foundational standard of care.

So we will get data over time from these trials as they read out about the combination and them being used together..

And we certainly are interested in that combination and generating additional data. I'm very proud of Jula's team, where we do have 2 ongoing studies looking at the combination of FILSPARI plus SGLT2.

So I think some of the few combination studies that have yet been initiated, we would expect that, that could potentially increase as other therapies are actually approved..

Our next question is going to come from Ed Arce from H.C. Wainwright..

A couple of quick questions for me. Firstly, with regards to the sNDA later this quarter for FILSPARI for approval, just wondering if you could confirm the length of the review period that you would expect 6 or 8 months or would that roll into sometime next year.

And then secondly, as I look at the PSFs quarter-over-quarter so far in last year and as those growth rates moderate a bit. I'm wondering if you can discuss some of the 2 inflection points that have been mentioned before later this year, the legal guidelines and the upcoming data analysis from ongoing trials especially the SGLT2 combo.

What impact -- and I guess this is a question more for Peter. But what sort of subjectively, what impact would you expect those to have on treating physicians as they get more experience with the drug..

Thanks for the question. Bill, why don't you take the regulatory question and then Peter, you can take the PSF outlook question..

Yes. We expect to have priority review out of for this sNDA that will be consistent with how the agency treated a predecessor that went just recently before us. In that case, it would be a 6-month review, so you'd have a Q3 decision. If we were a standard review, it would take until the end of the year. So in either case, we have a decision this year.

I'll pass over to Peter for the rest of your question..

Yes. Thanks for that question. I think there is really 2 elements that I would like to point you to with regards to the evolving landscape, with regards to the KDIGO guidelines as well as a broader label? And what would that mean for the potential for patient start forms in the future. I think there's 2 core elements.

One is the urgency to treat or better the urgency to change with further emphasis has to go lower proteinuria, as a level of [indiscernible] is still not where you need to be.

I think last year, the RADAR data got published from the U.K., it's more of [indiscernible] data and it shows that even with the proteinuria of 0.9, those patients actually have doubled progress to end-stage kidney disease compared to patients that had a proteinuria level of in average of 0.44.

I think this kind of data and then reinforcement in the guidelines further amplifies the urgency to change for those physicians and change that foundation that is currently ACE and ARBs and replace it with a much more efficacy treatment [indiscernible] and just to recall, I mean, the proteinuria benefit that FILSPARI had after 9 months was threefold [indiscernible] but after 2 years, it was actually tenfold.

So I think that is an important aspect. So the urgency to change, I think, is one aspect. The second one is really it allows for a broader patient population.

And what we have highlighted earlier is that we said at launch, we expect to have an addressable patient population for FILSPARI between 30,000 and 50,000, we think with the broadening of the label as well as further highlights of the guidelines to go to a lower proteinuria target. We think there is up to 70,000 addressable patients for FILSPARI.

I think those are the 2 core aspects I want to highlight with regards to the evolving landscape and what it means for the addressable patient population and potentially patient for FILSPARI..

Thank you, Peter.

Jula, is there anything that you'd like to add?.

Yes. Thanks. I think we have a couple of inflection points and Peter nicely highlighted KDIGO to treat patients earlier and diagnose them earlier. And then the SGLT2 combination, we know that combination therapy is going to be important in the future. So we think those are 2 things.

But the third thing that I want to point out is with regards to the earlier treatment, we have a trial called SPARTAN, where we utilized FILSPARI early after they first get diagnosed and the RAS naive.

We presented some of that data at ASN and it shows earlier, we see an 80% reduction in proteinuria most of the patients getting into complete remission and no change in eGFR over 36. That trial has been continuing. We'll have additional data on that over the years.

But I think that's an additional point as far as treating patients earlier in their disease course..

Yes. Thank you, Peter and Jula.

Maybe if we just take a step back for a moment, if we put ourselves towards the end of 2024 and you assume that we have a full approval with a potential broader label just as the KDIGO guidelines could potentially lower the target and really increase the dynamism in the treatment of patients with IgA nephropathy, we really will be at the right place at the right time.

And if you think about also all of the clinical experience that physicians are getting with FILSPARI, there's one thing that we know from this launch and hearing from physicians and their patients who are on FILSPARI. It is a very rapid and consistent reduction in proteinuria. We believe that we'll be in the right place at the right time.

And I think our goal is to make sure that we continue to expand for new physicians to be able to get that clinical experience and we believe that positions us very strongly for future growth..

And our next question is going to come from Laura Chico from Wedbush Securities..

I'd like to shift gears and ask one on pegtibatinase. And Eric, your comments there about kind of the phenomena we see with orphan disease and the expansion of patient populations over time. I apologize if I missed this but do you plan to keep a patient registry with respect to HCU.

And kind of related to that, would you be able to disclose an identified patient number as you're going along?.

Great question, Laura. Yes, we do have a registry and we do continue -- we plan to continue that. We think that, that's an incredibly important source of information for the community. And it's really a great question around sharing patient information or identification.

It's certainly something we know others have done, we'll be looking at the potential for us to be able to do that as well. I can't commit to it today but absolutely something that our team is looking at..

And this will conclude the question-and-answer session of today's conference call. I'll hand the call back over to Anne. Please go ahead..

Great. Thank you, Jenny and everyone, for joining us for our fourth quarter and full year 2023 financial results call. We look forward to providing additional updates on our progress. Have a great rest of your day..

And this concludes our call. Thank you for your participation. You may now disconnect..