Q4 2023 Travere Therapeutics Inc Earnings Call

Participants

Anne Crotteau

Jula Inrig; Chief Medical Officer; Travere Therapeutics Inc

Peter Heerma; Chief Commercial Officer; Travere Therapeutics Inc

Christopher Cline; Chief Financial Officer; Travere Therapeutics Inc

William Rote; SVP, Research & Development; Travere Therapeutics Inc

Greg Harrison; Analyst; Bank of America

Anupam Rama; Analyst; JP Morgan

Tyler Buren; Analyst; TD Cowen

Carter Gould; Analyst; Barclays

Maury Raycroft; Analyst; Jefferies

Liisa Bayko; Analyst; Evercore ISI

Vamil Davin; Analyst; Guggenheim Partners

Alex Thompson; Analyst; Stifel

Mohit Bansal; Analyst; Wells Fargo

Yigal Nochomovitz; Analyst; Citigroup

Ed Arce; Analyst; H.C. Wainwright & Co.

Laura Chico; Analyst; Wedbush Securities

Presentation

Operator

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.

Anne Crotteau

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 us 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 statements. 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 Servier 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 the year as we worked 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 sorry, at the first and only non-immunosuppressive treatment option for people living with IGA nephropathy or IDNs for decades, people living with, again, most of whom are diagnosed in their 20s and 30s and on average face kidney failure in 10 years and 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 those Ferrari as a foundational treatment with a superior proteinuria reduction and accrual of kidney preservation benefits following the grant of accelerated approval.
Our team quickly initiated our comprehensive commercial launch plans and work throughout the year to lay a strong foundation for fuel sorry, 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 fluorspar is the only recent launch in that 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'd 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'm 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 more picked about nice 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 home, assisting levels.
With better diagnoses and a future where an effective treatment is available. We believe this may grow by 50% or more over time last year. We and generated additional exciting data from our Phase 1 to compose study, which further demonstrate the potential for patent about next to become the only disease-modifying therapy for HCU.
With these data, we worked closely with regulators to align on a Phase 3 program utilizing total home assisting 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 equal story 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 Philstory. Of note we are on track to submit our SNDA this quarter to support conversion.
It feel sorry, for accelerated approval to full approval for IDNs in the US. Together with our partner, CSL V4, we expect an opinion on the conditional approval of fuel spike in Europe from CHMP later this quarter. We're optimistic that this will be positive.
And with our recent agreement with reanalysis. We are looking forward to eating their development plans to ultimately enable access to fill story in Japan and other regions in Asia where, again is an even more prevalent disease and leading cause of kidney failure.
And importantly, we are excited about the opportunity we have with Take-Two that makes 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 3 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?

Jula Inrig

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.
It was real story. We completed the two year double-blind dosing periods for our studies in FSGS. And again, it's important to highlight that our studies are the only ones in this space that use a maximally optimized active comparator, setting the bar highest in the field, the results, which clearly demonstrate a robust proteinuria reduction and preservation of kidney function.
And again, we're simultaneously presented as a 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 Jill story can play in long-term kidney function preservation for patients with IgA nephropathy.
What has resonated with nephrologists is that so far is the only approved non immunosuppressive treatment for IGN. And it's the only molecule that works by simultaneously blocking the two key pathogenic pathways in the kidney and OP-1 one and angiotensin two that both work together to drive damage and kidney function loss.
You'll see a 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 so far has demonstrated a long-term accrual of benefit on EGFR.
In the Protect study at one year, there was a 1.7 mil per minute favorable effect on absolute EGFR with Bill Sperry compared to maximally titrate herbicide. And that benefit increased to 3.7 mils per minute greater EGFR at two years.
Importantly, the rate of loss of kidney function in year two compared to year one was significantly slower for Phil Sparks treated patients suggesting a potential additive benefit with longer term treatments. 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 two year data from the PROTECT study in August shows that so far is superior to historical RASP inhibitors and it's 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 Phil Sparks where they see significant reductions in proteinuria and the ability to safely use so far with their patients chronically.
We believe this cements the role that so far I can play by replacing RASP inhibitors as foundational care for those at risk of rapid disease progression, we have 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 fuel card from accelerated approval to full approval for again.
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 IVF 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 so far used as a foundational care in IBM, essentially replacing the historical role of RASP 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 fuel Spark 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 Phil Sparks when seeking treatment options that can provide long-term kidney function preservation.
Additionally, we believe so far is likely inclusion in the soon to be released, KDIGO guidelines should further standardize you fulfill price with the nephrology community and potentially result in earlier treatment as positioned and up to date and recent peer reviewed IVF treatment articles we anticipate still scarred so far will be described as a foundational treatment in the K/DOQI guidelines.
We also believe that the proteinuria target for treating IBS overall will be lower, 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 Spartacus and SPARTAN studies, which are designed to show so far, it can be safely used in combination with other medicines such as SGLT2 inhibitors and that patients may benefit from earlier use of Pillsbury. Such data will further support the progress towards Pillsbury achieving foundational care.
Beyond the US, we have continued to work closely with our partners at CSLP. four on the conditional marketing authorization applications that is currently under evaluation in the UA, EU. Following a procedural clock stop to review the two 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 our analysis provides still story with a regulatory pathway that has the potential to deliver fuel story 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 increasing utilization of Hillsboro for again 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 in FSGS.
We are taking a measured approach to evaluating our datasets and working with the community to reengage the FDA later this year toward the goal of ultimately being able to submit to have an FSGS indication added to the fill sparring label. We anticipate being able to provide an update on this work late in the year. As Eric highlighted earlier, our enthusiasm and passion about needs continues to grow.
We were pleased to achieve alignment with regulators on the design of our Phase 3 program and to reach our goal of initiating the Phase 3 Harmony study before year end. This study employs an innovative design with measurements very similar to our highly successful Phase 1(2) study, which we believe provides a high probability of success as a registration enabling study.
The Phase 3 Harmony study is designed to recruit up to 70 patients with HVU. and evaluate change in total home of 15 from baseline to week 6 to 12 as the primary endpoint. This is the measurement for which we saw a 67% reduction in the high dose cohort in the composed study.
Patients will be followed in the double-blind period for 24 weeks in total to establish durability of effect and the robust safety database. Maximize 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, where there is a protocol like diet liberalization substudy for eligible patients who have well-controlled total home assistance.
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 and they may be able to increase protein intake while taking about knees, 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 PET to badness 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.

Peter Heerma

Thank you. Looking back in 2023, we made robust progress. And what we have outlined during our launch call in February last year. Physician fills Virena again as the future foundation of care for patients at risk of rapid progression through educating our nephrology targets. Securing broad access and ensuring a positive initial sales by experience for patients and physicians.
And I'm really proud of 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 unexpected REMS program for liver monitoring.
At the end of 2023, nearly 5,700 nephrologists with our sales team and 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 Asian patients in the US.
These efforts resulted in strong and steadily increasing demand with increasing breadth and depth of prescribing nephrologists. In particular, in the fourth quarter, we built strong momentum, fulfill spot demands.
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 PSS. after a as in Kidney Week for the confirmatory PROTECT study results were presented and published.
Importantly, we also received further validation of the Shell salary profile from thought leaders, which was evidenced by increase in key opinion leader prescribers. We ended the fourth quarter with 459 new PSS, which demonstrated quarter over quarter growth for each period in 2023.
In fact, this is the first REMS really for all the product. It has shown a continuation of growth in demand during each period of the first in the first year of loans. In total, we received more than 1,450 patient start forms in 2023, which clearly indicates to us that 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 US lives. In the fourth quarter, we added about 180 new fills very specific formulary formularies.
And overall, more than 1,000 formularies have included shows Paris with authorization criteria that are generally consistent to the satisfactory level. And if we account for plants that didn't yet included stores, Barry, but have a clear best pathway for coverage that total is about 89% of U.S. lives.
Following our team's quick adjustments to improve patient education and provide further support for the liver monitoring ramps 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 a patient start forms.
This also led to a growing number of reimbursed patients initiating therapy during the quarter, and we are hearing almost on a daily base from patients and physicians, how impressed they are with the results that they have shared with Philfury.
These results are consistent to what was observed in the Protect trial with rapid and sustained proteinuria reductions with a safety profile similar to ACE inhibitors and ARBs. This is encouraging for patients that started using satisfied and likely why we are seeing heightened compliance rates so far in the loans for these accomplishments, we saw this in a significant increase in national spot sales.
In the fourth quarter, we reported approximately $15 million in net product sales, which result in nearly $30 million for the year. By Alba and Thiola EC also, we made some contributing approximately $25 million in net product sales in the fourth quarter.
We recently learned of an approval of a generic sale that you see was a narrower label, and we will continue to monitor what impact it 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 six weeks of the new year. I'm pleased to see our strong fuel storage performance continue. Our team is ready to show the true potential of horsepower in this new year, and we have multiple inflection points throughout 2024 that provides confidence in continuing growth.
Let me highlight four areas that I'm 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 broad label would provide greater support for physicians to prescribe to aspire to more of their patients.
Second, as Julie mentioned earlier, we anticipate the full study will be included in the global clinical guidelines scheduled to be updated this year. This would potentially provide uniform guidance for physicians to choose Pillsbury as an early treatment for their patients.
Third, additionally, if the guideline revision emphasizes earlier intervention by lowering proteinuria targets, it would likely amplified the urgency to diagnose and treat patients earlier. We believe this will increase the number of patients that would be eligible for study.
And importantly, a broader label together with a potentially lower target to treat earlier in the guidelines would allow us to establish Torstar as a foundational treatment in a larger addressable patient population.
And fourth, we expect the additional clinical evidence deal I highlighted earlier will ultimately provide additional support for physicians to treat earlier still sorry 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 Sourcefire's prospect 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 updates with.

Christopher Cline

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 thus far in IGA nephropathy and the advancement of our Phase 3 development 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 thus far in 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 in the same period in 2022. The difference is largely attributable to the continued advancement of our pact about new clinical programs, partially offset by reduced investment in our first-party Phase 3 programs following the readouts from the two 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 in 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 for sorry, 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 in the same period in 2022. During the fourth quarter, we recognized $11.4 million in restructuring fees related to the 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 2022. As of December 31, 2023, the company had cash, cash equivalents and marketable securities of $566.9 million.
Looking ahead, we expect meaningful growth in net product sales, which was far in 2024. And we look to achieve non-GAAP operating expenses below $400 million for the year. We also anticipate meeting milestones both thus far impacted by mix that will result in us making expected net payments of approximately $50 million during the year.
With our strong balance sheet expected growth until expiry revenues and measured investments, we currently expect that our cash balance can support operations into 2020.
I'll now turn the call back over to Eric for his closing comments. Eric?

Thanks, Chris. We are entering a new phase of growth for Tracleer. Our organization is well positioned with a strong financial foundation to continue advancing So sorry and paid about ACE has potential future treatment standards for their respective rare kidney and metabolic disorders.
Moreover, these global markets collectively are projected to exceed $10 billion in the coming years. Our unrelenting drive is based on our desire to deliver life-changing therapies to people affected by again HCU and potentially FSGS. who historically have had little to no innovation for their condition.
We see near term and long term growth through the following. The continued strong execution of our field force launch, the expected conditional approval of sparsentan in the EU and full approval, I feel sorry, for again in the US with potential broader labeling, updated IVF treatment guidelines and further data generation to reach the growing number of patients in need of a better therapy.
Finally, I am particularly excited about the advancement of our development program for patent about Mace 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 ACU and enrolling the Phase 3 HARMONY study with the goal of achieving top line data in 2026.
So let me now turn the call over to Anna to open up the lines for Q&A. Anne?

Anne Crotteau

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

Question and Answer Session

Operator

Thank you. (Operator Instructions)
Joseph Schwartz, Leerink Partners.

Great. Thanks very much, and congrats on all the progress on I guess I'll ask on Philbury, how much does the higher hurdle that Phil Sparks had in the Protect trial seemed to resonate with the prescribing community. Today 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 it Phil Spires 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 could also comment on what we saw coming out of ASN where there was much more discussion about the protests trial and trial design?

Peter Heerma

Yes, I good question, Joe. I would say the conversations I've had with physicians. And I think it's also being in line with the market research results that we saw. But if we if we outlined the study design of Protect and the understanding of like an active control arm is understood.
There's really like great appreciation for the a very robust result that we have you I highlighted earlier in the call, like 1.7 mil minutes per year improvement. And then the second rig is actually 3.7 mil per year. So an accumulation of benefit over time. And I think that is something that the physicians understand design really, Mikhail.

I'll get back in the queue.

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

Jula Inrig

Yes, I think it does take some education because all the other trials are comparing to a not fully optimized standard because we know historically 50% and really all the other trials are on track. But yes, we have a higher hurdle.
And so for now, see that comparison in the float, 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 benefit that we can see we only get a two-year snapshot, but you know that if you have a benefit that's better in year two versus year one, the metrics that continue to improve year over year does take some time, but they get it once they spent 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 and throughout the two years.

Very helpful. Thanks.

Operator

Greg Harrison, Bank of America.

Greg Harrison

Hey, guys. Good afternoon. Congrats on the progress, and thanks for taking the question. Just thinking through the again treatment landscape and when it comes to the compare and 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 you're hearing from thought leaders about the evolving treatment landscape and the importance of EGFR and proteinuria drilling.

Jula Inrig

So first, I'll start with proteinuria and eGFR or 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. We're evaluating and looking at risk as well as response to treatment over time as the proteinuria changes can occur more quickly versus the DFR changes require many years to show.
And I would say importantly, multiple data sets show a strong correlation between growth carry reductions over time and risk of kicking off. 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 rates that still remain at risk if they've got 0.44 grams per day, so getting post patient closer to normal with regard to their troponin area is very important to realize we are one of three patients and so far in PROTECT achieved complete remission of proteinuria and filtration, both reductions in proteinuria and EGFR preservation that accrues over time. I think all those are important factors that take into consideration.

Greg Harrison

Got it. That's helpful. Thanks a lot.

Thanks, Greg.

Operator

I'm sorry, go ahead.

No, please go ahead. I was just thanking the last person.

Operator

Anupam Rama, JP Morgan.

Anupam Rama

Hey, guys. Thanks so much for taking the question and a little bit more of a kind of an acute question. As we think about skills Bharti 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. And let me just first say that Peter's team has done a really great job starting the year strongly. We've been 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 some of those dynamics in more detail. Peter?

Peter Heerma

Yes. Happy to Eric. Yes. As I mentioned earlier, I think the across the three core fundamentals of launching a product that we made really substantial progress apparel and in particular, like Asia and I think really allowed for building up momentum.
We saw like a certain increase of prescriptions, in particular from thought leaders. So we also saw like a good progress in our pull through and getting patients home page product. And I think across the fundamentals, we see that the continuation of progress in the first six weeks of this year as well.
I think to your more specific question, like what is the insurance resets and reauthorization criteria, meaning for the gross to net in the first quarter for this is the first year, we will offshore storage that can be a new earning. 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.

Anupam Rama

Thanks so much for taking the questions.

Thank you.

Operator

Tyler Van Buren, TD Cowen.

Tyler Buren

Hey, guys. Good afternoon. Thanks for taking the question. But so is part of the SNDA submission by the end of the first quarter for the full approval for Sparlon again, does that include a request to have the black box and REMS warning removed? And if so, can you describe to us how you supported that Riquent?

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.

Jula Inrig

And so I want to highlight that across our development program and for your commercial launch, including patients who have had some of our trials on treatment for up to 10 years. We have a couple of cases program with departments.
And now I get I note that there isn't his door for press removal of them honestly, I'm sure that we certainly are going to advocate for the best process for patients which could change in the free.
Bill, want to comment further on our process.

William Rote

Yes, with the in 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 US NDA this quarter, which will give the full two year data in the PROTECT study.
Both of those give us a launching point to begin the dialogue around potential modification of the REMS program. And 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.

Operator

Okay. Carter Gould, Barclays.

Carter Gould

Good afternoon and thanks for taking the question and congrats on the pickup in sales. A lot a lot, a lot of mentions of momentum and inflection on the call there on 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 forms?
Probably a fair characterization of what we should expect going forward until those inflection points that Peter mentioned sort of hit that does seem like those are back-end weighted. Any color commentary would be appreciated.

Thank you, 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, but what we can expect to see moving forward?

Peter Heerma

Yes.I think, Gould, for the question, I think it's the characterization that you have made, you have to take it into context of a prescriber base that had very little innovation in the last 30 to 40 years. And so I think the adaptation, but it takes time to educate the broader 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. And I think what I called out earlier is that this is the first reason ran from July. We see that continual growth. I think that is something that is the data.
We expect to hear the guidelines to be updated, that there 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 yes, I think you have to take it into consideration with an audience that is maybe not used two different innovation and really requires like education and with the experience that they're 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 of launch had a continual growth that we saw and we were pleased with.

Carter Gould

Very helpful. Thank you.

Operator

Maury Raycroft, Jefferies.

Maury Raycroft

Hi. Congrats on the progress and thanks for taking my question on 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 two year data to the EU, which led to the clock stop.
So is it possible you could get full approval in the EU? I guess is there any possibility for that or will it still be conditional and has the EMA provided any feedback after reviewing your two year data?

Maury? Thanks so much for the question, Bill. I will pass it over to you.

William Rote

Sure. Well, we remain optimistic about the positive CHMP decision that will be made this this first quarter. The two 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 was a discussion of potential full approval and there are aspects of the data package that they don't have yet on the full tables figures and listings work provided some more of a top line and look at the two year data. So I wouldn't expect a full approval with this round.

Maury Raycroft

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

William Rote

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 toward full approval.

Maury Raycroft

Got it. Okay. Thanks for taking my questions.

William Rote

Certainly.

Maury Raycroft

Thank you.

Operator

[Tim Lugo] William Blair.

Hey, team, this is John on for Tim. Thanks so much for taking our question. 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 a comp might be required?

John, thanks for their questions. Bill, I'll pass it back to you.

William Rote

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 is a controversial aspect of this. So I don't anticipate that the agency will panel an advisory committee. Certainly if they do, we will be ready on you.
The second part of your question was the timing. Generally, the agency will let sponsors know within 60 days of submissions 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.

Very helpful. Thanks.

William Rote

Certainly.

Operator

Liisa Bayko, Evercore ISI.

Liisa Bayko

Hi. Thanks for taking my question.
Do you have any more color on when the new guidelines are, it will be on relief.

Jula?

Jula Inrig

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

Liisa Bayko

Okay. And you mentioned compliance rates were good. And can you speak to kind of where you are with compliance and also and, you know, can you describe gross-to-net for the year, like what and what kind of average for the years that you should be thinking about or what was normalized and the color there would be helpful.

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

Peter Heerma

Maybe I'll take the question on the compliance and Chris, maybe you could take the gross to net on some of the compliance rates like if you if you look at benchmark for chronic disease without a nonsystemic symptomatic disease, overall compliance rates are not very high.
We see with Phil's Barry, so far it is actually really high. It's higher than what we anticipated, especially when you also have a REMS program with close monitoring that requires monthly liver testing. So far, we see very strong compliance rates.
I think it's key also to the experienced patients are having in this for the first time, they see it as being controlled to the target levels. And I think you have to take into considerations 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 are not yet on the target.
And I think now we're still flowery. They feel like, hey, you know what, we are able to reach that already. But I think it is motivating patients to continue to use the product. And well, I think we see also high compliance rates.

Christopher Cline

And Liisa, just on the gross-to-net, which we've been pleased with how we've seen things meet our expectations that having a mid to high teens growth in that building 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 to remain in that mid to high teens level.

Liisa Bayko

And then can you comment at all on like how many patients are on kind of exiting 2023 and Philsfury.

We've not provided guidance for any RKPI.s on a number of treated patients. And I think Peter can talk about directionally what we were seeing as we as we ended the year, but at least we're going to continue to provide updates on TSS on payer coverage and on revenue at this point in the launch.
Peter, you want to provide any thoughts anything further tonnage?

Peter Heerma

This question might be a good idea. And as I mentioned earlier, I think we are making robust progress on from all the fundamentals, including the pools you're getting patients on base products. I think the process is well within what benchmarks which you would expect from a from rare disease products. So I think we will see that continuation and that will be reflected by revenue as well to Eric's point.

Liisa Bayko

Okay, thanks.

Operator

Vamil Davin, Guggenheim.

Vamil Davin

Great. Thanks for taking my question. Maybe just a couple of follow-ups on the payer side sort of thing, Peter, I think you mentioned in your prepared remarks that payers are there on sort of acting generally consistent with the label in terms of the patients that they're from reimbursing there before.
I'm curious if maybe you can just give a little more detail there. And 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 had was 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'd have to wait until sort of the 2024, 2025 cycle starts up in terms of formulary status or our new authorization?

Alright. Peter, I'll hand this over to you.

Peter Heerma

They are very good with regards to authorization criteria. I mean, there's always certain aspects to payers expecting to soon. And so I think where we where we are is that especially in the beginning when we got the label and the label was kind of save on patients had rapid progression of disease with regards to proteinuria as states like generally 1.5.
And we are seeing that payers in most of the authorization criteria refer to the label, but also referred to refer to the clinical guidelines and it has lower proteinuria targets that allow sort of broader use and apply to my earlier point in the call with a further lowering of the protein urea targets within the Duke alliance, the company like a broader label fulfills, Byron, it was allowed and also for a broader patient population that's eligible for pain 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?

Peter Heerma

Yes. So I think it speaks a little bit to what I said was a further lowering of the urea targets and then also a broader label where there is no restriction in proteinuria that authorization criteria or 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 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 times that we have in the strong base that we have in forming, those provides a very strong position, especially since we have like the highest standards for solid design
For me this is the only study that has an active comparator, which is basically the gold standard. How payer is a evaluating new products. So I think we are in a strong position with regards to lead time as well as study design and how payers are evaluating that involving landscape.

Vamil Davin

Okay. Thank you.

Operator

Alex Thompson, Stifel.

Alex Thompson

Yes, great. Thanks for taking my question. I want to pivot a little bit to take the baton this year. 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 1(2) on how well identified are these patients, if this is a 12 week, primary end point with the top line is the 2026 readout conservative at this point? Or how are you thinking about that? Thanks.

Alex. Thanks so much for the question and also for the focus on the picked about Mace program. Jula, I'll turn that one over to you.

Jula Inrig

So thanks. And we think this is an exciting trial design that focuses on changes in total MMO-15, not just it six to 12 weeks, but also looking at durability of effect, but we did a 24 week study and in 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 from compose at 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.
And we are intentionally moderating our enrollment initially to ensure we have a good experience with 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 you can comment on the enrollment period is for screening that it helps explain why the timeline may be a bit longer than what people would typically set for that for this type of trial?

Jula Inrig

Yes. Thanks. Because it is a six month trial plus we have a 10 week run-in period where patients get screened to make sure they qualify as well as standardized. And that's really to trying to optimize our chance of success that patients have and understand the trial that they need to keep their diet chemo, 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 events than what you first stated.

Yes, and we'll certainly look to move swiftly on this, but we are for all the reasons that you've explained. We've been very thoughtful around the time line 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 in unit 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 and 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.

Alex Thompson

Yes, you know, 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, which sites, et cetera. So I think Julie's team has done a really great job of ensuring how we can enable success in the Harmony trial. So I think, Bill, you can talk about a high level of the powering.

William Rote

Yes, no, certainly, and appreciate the question. We're very confident in the powering of the study and recall in Jula's initial remarks, you mentioned the 67% reduction in total home assistance that was observed in Phase 2.
So with that level of efficacy, even with a significant diminution in the treatment effect for 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.

Alex Thompson

Great. Thank you.

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

Operator

Mohit Bansal.

Mohit Bansal

Okay. So I did not hear you, and that might tell you about that. Thank you very much for taking my question and congrats on the progress. I 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 farms coming from third quarter, 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 or so. Is this because you are converting a lot more of those patients from into up 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 the bank's price increase? Thank you.

Okay, thanks. So much for the questions. Peter, I will turn that over to you.

Peter Heerma

Yes. (inaudible) So as I mentioned, like one of the core fundamentals is making sure that patient start forms transition ultimately to a patient on products and in particular based on paid products or you continue to increase the revenue.
And I think what you saw in this quarter is that we that we made robust progress, in particular also in the pocket of patients that we described in the earlier quarter, which that required some additional handholding and education with regards to the REMS process.
Until we, as I mentioned, like the patient REMS certifications in the first 14 days has increased quite substantially, and that allows patients to go through the process and get to a base product more quickly.
So good progress there. To illustrate earlier point, we don't provide further details on how many patients we have on product, but I think the transition from business platform to ultimately get personal pay product, we made significant progress.
On the second question with regards to price and price increase, and we have 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 AGS-004 and different preservation as well. So we thought it was justified to have a price increase for this year.

Got it. 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 you're 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 on how we're doing at the end of Q1.

Mohit Bansal

Thank you.

Operator

Yigal Nochomovitz, Citi.

Yigal Nochomovitz

Hi Travere team. Thank you very much for taking the questions. 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 finding 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, and again, just wondering, obviously, there's been a lot of visibility around some of the newer mechanisms, anti B-cell mechanisms. Wondering whether Phil Sparks governments positioned as a foundational additional therapy may or may benefit from a combo study using the B-cell modulators on top with those bari at a future point. Thank you.

Great. Thank you for the question, and Jula I'll turn those over to you.

Jula Inrig

Thank SIFSTX. and we are continuing to do our process with our data and external data sets, putting our trials in the historical context. With regards to the FDA, this is a partnership with NextCure and much of the patient organization with academics and the FDA.
And it's called Paris, all there's a website, it's public. 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 pathway for FSGS. and we plan to reengage the FDA following their final analysis and decision on what those endpoints should be under this Paris all group and they're targeting ASN. for that time line.
And then your second question is around some of the newer agents and how those priorities should be placed. And I think it's really going to be an exciting few years for IGA nephropathy patients at some of these new therapies Most of which target different parts of the injury Cascade contributing to again, 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 immune modulating agents are being used on top of standard of care foundational treatment. And that's worth of bari plays a foundational role because it targets the injury in the kidney and the response to the GDIGH. deposition and protects against further damage and really weren't really aligned with the KOLs who need to target two things ongoing damage in the kidney with foundational treatments.
And to your point, you could potentially add another agent that targets upstream pathways that's additive as far as other trials. I think it's important to realize every other trial is studying a new agent on top of standard of care and many of those trials now because they're still sorry, superiority over ACEs and arms they're being allowed as part of the foundational standard of care. So we will get data over time from these trials as an 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 Joe's team for. We do have two ongoing studies looking at the combination of those 40 plus SGLT. two. 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.

Yigal Nochomovitz

Thank you very much.

Operator

Ed Arce, H.C. Wainwright.

Ed Arce

Well, everyone, thanks for taking my questions and congrats on another quarter of progress. A couple of quick questions for me. Firstly, with regards to the ES NDA later this quarter, so for aspiring for approval, just wondering if you could confirm the length of the review period that you would expect six or eight months or would that roll into sometime next year?
And then secondly, as I look at the PSPSS. quarter-over-quarter so far in last year, I mean, as those growth rates moderate a bit, I'm wondering if you can discuss some of the two inflection points that have been mentioned before later this year that could legal guidelines.
And in the upcoming data analysis from ongoing trials, especially the SGLT2 combo arm, what impact, 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?

Yes, and thanks for the questions of Bill, why don't you take the regulatory question and then Peter, you can take the PFS outlook questions?

William Rote

Yes, we expect to have priority review out of them for this NDA. That will be consistent with how the agency treated a predecessor that went just recently before us. In that case, it would be a six month review so you'd have a Q3 decision. If we were standard review, it would take two to the end of the year. So in either case, we have a decision this year. So I'll pass over to Peter for the rest of your questions.

Peter Heerma

Yes. Thanks for the question. I think there's really two elements that I would like to point you to with regards to the evolving landscape with regards to the EU guidelines as well as a broad label. And what would it mean for the potential for a patient start forms in the future?
I think there's two core elements. One is the urgency to treat or better the urgency to change with further emphasis. We have to go lower proteinuria at the level of loan is still not where we need to be. And I think last year, the radar data published from the UK, some Blood Registry 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 have a particular level of an average of 0.44. So I think this kind of data and then a reinforcement in the guidelines further amplifies the urgency to change for those positions and change that foundation that is currently in ours and replace it with a much more efficacious treatment.
Slide shows bar. Just to recall, I mean, the proteinuria benefit that Phil's Barry had after nine months was threefold 50, 50, but after two years, it was actually 10 for us. So I think that is an important aspect of 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 for you is that we have at launch, we expect to have an addressable patient population for fluorspar in between 30,000 and 50,000, we think with a broadening of the label as well as a further highlighted the continued guidelines to go to a lower bottom urea target.
We think there is up to 70,000 addressable patients for transpiring. So I think those are the two core aspects I want to highlight with regards to the evolving landscape and what it means for the addressable patient population, potentially business portfolio totals Fiery?

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

Jula Inrig

Yes, thanks. I think we have a couple of inflection points and Peter nicely highlighted. Can you go to treat patients earlier and diagnose them earlier on the SGLT2 combination? We know that combination therapy is going to be important.
If you're so we think those are two things. But the third thing that I want to point out is with regards to the earlier treatment, we have a trial called Sparton where we utilize I'm sorry, our early after they first get diagnosed and the Ras 90, we've presented some of that. It had a it can.
And it shows the three earlier we hit 80% reduction in proteinuria, most of the patients getting into complete participants 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, that maybe if we just take a step back for a moment. If we 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 Contigo 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 feel sorry, there's one thing that we know from this launch and hearing from physicians and their patients Grantsdale story.
It is a very rapid and consistent reduction in proteinuria. We believe that will be in the right place at the right time. But I think our unit. 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.

Ed Arce

Great. Thank you so much. That's very helpful.

Operator

Laura Chico, Wedbush Securities

Laura Chico

Hey, guys. Thanks very much for taking the question on. I'd like to shift gears and ask one on pet about newness 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 HCHCU. And kind of related to that, would you be able to disclose an identified patient number as you're going along? Thank you.

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

Laura Chico

Thanks very much, guys.

Operator

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.

Anne Crotteau

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.

Alright.

Operator

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