Travere Therapeutics - Earnings Call - Q4 2020

Transcript

Speaker 0

Good afternoon, ladies and gentlemen, and welcome to Trevyor Therapeutics Fourth Quarter and Full Year twenty twenty Financial Results and Corporate Update. At this time, all participants are in a listen only mode. Later, we will conduct a question and answer session and instructions will follow at that time. As a reminder, this conference call is being recorded. I would now like to turn the conference over to your host, Mr.

Chris Klein. Thank you. Please go ahead, sir.

Speaker 1

Thank you, Katrina. Good afternoon, and welcome to Travea Therapeutics fourth quarter and full year twenty twenty financial results and corporate update call. Thank you for joining us. I hope you all remain well. Today's call will be led by our Chief Executive Officer, Doctor.

Eric Dubey. Eric will be joined for prepared remarks by our Chief Medical Officer, Doctor. Noah Rosenberg Peter Herrma, our Chief Commercial Officer and our Chief Financial Officer, Laura Klig. Doctor. Bill Roat, Senior Vice President of Research and Development, will join us for the Q and A session.

Before we begin, I would like to remind everyone that statements made during this call regarding matters that are not historical facts are forward looking statements within the Safe Harbor provisions of the Private Securities Litigation Reform Act of 1995. Forward looking statements are not guarantees of performance. They involve known and unknown risks, uncertainties and assumptions that may cause actual results, performance and achievements to differ materially from those expressed or implied by the statement. Please see the forward looking statement disclaimer on the company's press release issued earlier today as well as the Risk Factors section in our Forms 10 Q and 10 ks filed with the SEC. In addition, any forward looking statements represent our views only as of the date such statements are made, 03/01/2021, and Traveer 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?

Speaker 2

Thank you, Chris, and good afternoon, everyone. We were very pleased with the beginning of the year on a high note with the DUPLEX study recently achieving its interim proteinuria endpoint, And we look forward to discussing a bit more about that with you shortly. First, I would like to reflect on the excellent execution that we had in 2020. This is a direct result of our team members' hard work and dedication to our mission of identifying, developing and delivering life changing therapies to people living with rare disease. Our key objectives last year were focused on three areas aimed at strengthening our position as a leader in the rare disease community.

The first was advancing our two pivotal Phase III programs for sparsentan in FSGS and IgA nephropathy. In doing so, our goal was to continue to position sparsentan to potentially become a new treatment standard for these two rare kidney disorders if approved. Despite the ongoing pandemic, our clinical and operational teams have done a phenomenal job of ensuring patient safety and continued high quality in both the DUPLEX Study in FSGS and the PROTECT Study in IgA nephropathy. Furthermore, their efforts led to both studies achieving the key enrollment milestones necessary to enable top line readouts from the interim proteinuria endpoints, including PROTECT, which is now well ahead of its original schedule. Both of these interim readouts are designed to support potential accelerated approval and conditional marketing authorization submissions in The U.

S. And Europe beginning this year. The second key objective was building upon our established commercialization capabilities to identify new patients that may benefit from our approved products, as well as to begin preparing our organization for a successful launch of sparsentan if approved. I am pleased to report that we maintained supply and access for our patients throughout the pandemic last year. We also continued to identify new patients for all of our approved products.

In preparation for a potential launch of sparsentan, we furthered our understanding of the patient journey in both FSGS and IgA nephropathy. This includes a deeper understanding of patients' needs, where patients may be identified, the therapeutic profile physicians desire for their patients, and the future role that earlier diagnosis can play. Together with our established commercialization capabilities, we believe that these deeper insights provide us with a clear pathway to be successful in delivering sparsentan if approved. Our third key objective was to further diversify our pipeline through our disciplined business development efforts. In the fourth quarter of last year, we added to our pipeline TVT-fifty eight, a novel investigational human enzyme replacement therapy that is currently in Phase III development for the treatment of classical homocystinuria, or HCU.

Current treatment options for HCU are limited and ineffective for many. Preclinical data suggest that TBT-fifty eight has the potential to be the first disease modifying therapy in HCU. We believe this program is an ideal fit for our mission and expertise. It allows us to leverage our late stage development and commercialization capabilities to potentially deliver a new treatment option for people living with HCU. And it provides the potential for meaningful growth on top of sparsentan.

I am incredibly pleased with our organization's performance in 2020, which is even more notable given the challenges that we have all faced in adjusting to the COVID-nineteen pandemic. This execution led us to meeting or exceeding our objectives for last year. And importantly, it set us on a path for a potentially transformative year in 2021. This potential is driven by multiple exciting catalysts anticipated from our pipeline this year. As I mentioned earlier, our DUPLEX study in FSGS achieved its prespecified interim FSGS partial remission of proteinuria endpoint, or FPRE, after thirty six weeks of treatment.

Based on the data from the interim analysis, we intend to pursue submissions for accelerated approval of sparsentan for FSGS in both The U. S. And Europe. With the interim readout behind us, our focus turns to preparing for our upcoming regulatory interactions and further building towards our goal of delivering sparsentan as a new treatment standard in FSGS if approved. We look forward to engaging with regulators in the coming months and continuing our preparations for NDA and MAA submissions later this year.

The interim assessments from DUPLEX and FSGS has also increased our confidence in the potential for sparsentan to have a meaningful treatment effect on proteinuria in IgA nephropathy. The ongoing pivotal PROTECT study in IgA nephropathy remains on track to report top line results from the interim proteinuria assessment in the third quarter of this year. If successful, this milestone could be the next significant step towards potentially reaching our goal of delivering sparsentan as a new treatment standard in both FSGS and IgA nephropathy. While we certainly have a number of important updates planned for sparsentan this year, we do also expect preliminary data from our ongoing Phase III proof of concept study of TBT058 in HCU to become available later this year. We are excited to have this program now fully in house and to advance our understanding of the candidate and its potential in HCU.

Our goal throughout the year will be to identify the most expeditious path forward to help address the significant unmet need for patients in this community. Let me now turn the call over to Noah for an update on our clinical programs. Noah? Thank you, Eric, and good afternoon. I continue to be very pleased with the advancement of our pipeline programs and the execution of our clinical and operations teams.

As Eric mentioned earlier, we are excited about the recently reported results from the pre specified interim assessment in the ongoing Phase III DUPLEX study of sparsentan and FSGS. Since the top line announcement, we have engaged academic and community leaders in nephrology and patient advocacy. Many of these leaders have been responsible for directing and participating in clinical research for decades with the hope of driving advancements in FSGS. The feedback we have heard since announcing the top line data has been overwhelmingly consistent. For years, there has been a lack of innovation in treatment for rare kidney disorders.

And while there is still much to be contributed to the understanding of FSGS, there is a tremendous excitement for the potential that sparsentan offers. Today, we will not be providing additional details from the interim analysis as our need to continue to preserve trial integrity for the ongoing DUPLEX study remains. I would however like to highlight some key aspects of the program that have helped formulate our view over time. First, sustained progary reduction has long been recognized as a primary treatment goal amongst nephrologists treating FSGS, and it is not easily achieved. When designing the DUET study and subsequent to DUPLEX study, we worked closely with the Neptune consortium to derive the clinically meaningful FSGS partial remission of proteinuria endpoint or FPRE.

This is defined as urine protein to creatinine ratio, UPC, less than or equal to 1.5 gram per gram and a greater than 40% reduction in UPC from baseline. This foundational work demonstrated that in pooled analyses of four FSGS cohorts from independent trials, patients achieving FPRE or complete remission had meaningfully better kidney survival. Importantly, this provided for the establishment of a clinical measurement that would provide a strong link between proteinuria reduction and preservation of EGFR for kidney survival and potentially support regulatory submissions for accelerated approval. It also allowed us to create sufficient modeling with sparsentan to design our Phase III DUPLEX study with confidence in the link between FPRE at thirty six weeks and eGFR following one hundred and eight weeks of treatment. We now have encouraging interim data from DUPLEX, the largest interventional study ever on in FSGS.

It showed that treatment with sparsentan demonstrated a statistically significant response on this clinically meaningful FPRE measurement compared to the active control of irbesartan, which is considered one of the standards of care, but not approved for FSGS. Of note, the interim analysis reported that treatment with sparsentan resulted in a sixty percent greater relative likelihood of achieving FPRE compared to irbesartan. These results are consistent with the data generated from our Phase II DUET study in FSGS. In DUET, sparsentan demonstrated an increasing response to FPRE and a durable and sustained proteinuria reduction out to eighty four weeks of treatment in the open label extension. This reduction in proteinuria was associated with a stabilization of EGFR over an extended period in DUET.

We also have a strong understanding of sparsentan safety and tolerability profile to date. We are fortunate to be able to draw from a comprehensive safety database of both ongoing and completed studies that extend beyond 600 subjects in multiple indications throughout the program's clinical history. In the DUET open label extension, we have followed patients for a median of more than four years, with some going out beyond six years. This has provided critical insight into the drug's mechanism and how it performs over an extended period. And most recently, the interim assessment from DUPLEX indicated sparsentan has been generally well tolerated and the overall safety profiles in the study to date have been generally comparable between treatment groups.

This is very encouraging interim data from this ongoing Phase three study. Finally, sparsentan acts as a high affinity dual acting antagonist of both the endothelin Type A and angiotensin II Type I receptors. Both the ERA and the ARV components of sparsentan are well characterized and act on independent pathways that are well understood by the nephrology community. There has been a consistent and growing body of evidence, including the recent interim analysis from DUPLEX that supports the importance of targeting not just one, but both of these pathways together to optimize treatment for patients. There is a clear need for new treatment options in FSGS, and we believe the interim proteinuria assessment supports the potential for sparsentan to become a new treatment standard in FSGS if approved.

We look forward to engaging in the coming months with both U. S. And European regulators on our plans for accelerated approval and conditional marketing authorization submissions. In parallel, we are continuing to prepare these applications with the goal of entering submissions for FSGS in the 2021. As Eric mentioned, the interoprotiri data also provide us with further confidence in our approach developing sparsentan for the treatment of IgA nephropathy.

As we've outlined previously, we believe FSGS and IgA nephropathy share a common pathway where proteinuria plays a key role in both diseases. And this is important due to the fact that ERA blockade on top of renin angiotensin inhibition has been demonstrated to lower proteinuria in multiple renal populations. We believe these facts combined with the anti inflammatory properties of sparsentan that have been seen in our preclinical work in IgA nephropathy will play an active role in the disease and provide a strong rationale for sparsentan to be successful. We continue to see strong enthusiasm from the nephrology and patient communities for a new non immune suppressant based treatment option to slow progression of disease. As a result, our pivotal Phase III PROTECT study in IgA nephropathy continues to advance and the study continues to enroll towards completion.

Importantly, we remain on track to report top line data from the interim protein assessment in the third quarter of this year. Finally, the TBT058 program continues to advance in the Phase III dose escalation study. Our goals for this TBT05A program will be to gain a better understanding of optimal dosing to understand its potential to meaningfully reduce homocysteine levels and to identify the best regulatory path forward that would allow us to address the significant unmet need for patients in this community as quickly as possible. Similar to our other clinical trials over the last year, we are continuing to monitor the potential impact of COVID-nineteen on the TB T058 study, which could result in an adjustment to the timing of any data becoming available. Based upon what we know today, we continue to anticipate preliminary data later this year.

Overall, I am incredibly pleased with the progress we have made with our clinical programs and with how our execution has positioned our studies to potentially generate meaningful hope for patients that desperately need new treatment options. I'll now turn the call over to Peter for the commercial update. Peter?

Speaker 3

Thank you, Noah. Our commercial organization had one of its strongest performances yet in 2020. The members of our sales team are driven by their passion to make a difference for the patients we serve. And as a result of their hard work, we have quadrupled the number of patients treated with our approved products over the last six years. Despite the ongoing challenges of COVID-nineteen, we have maintained our patient inspired focus and ensured uninterrupted supply of our approved therapies and steady support and access for patients.

And we continued to effectively identify new patients through virtual engagement with HCPs. Our organic growth in 2020 was consistently driven by new patients initiating therapy across all approved products as well as a moderate increase in patient compliance. This translated to a 13% increase in net product sales over 2019, exceeding our guidance of mid single digit growth set in the 2020. Demand for the EC formulation of Thiola remains steady. The bile acid portfolio remains strong and coal bound continues to see demand driven by cumulative efforts of our coal bound team to educate pediatric geneticists on the importance of treating the hepatic involvement of cell record spectrum disorders, as well as our commitment to provide genetic screening to cholestatic patients.

Looking ahead, we will continue to monitor for any COVID-nineteen related impact on potential shifts in patient insurance coverage as well as patients' ability to see their physicians. As has been typical for us in the years past, we anticipate uneven growth in the net product sales throughout the years, including anticipated higher gross to net discounts in the first quarter, driven by insurance coverage changes in the beginning of the New Year. Importantly, we believe there will be continued demand for our approved therapies and that we can achieve mid single digit growth for the full year of 2021. We continue to fuel our continued success with both THIOLA and COLBAN as strategic strengths to leverage for future commercialization of our development programs if approved. To this end, we were pleased to recently enter into a co promotion agreement with Albreo for of the Fixibat product in The U.

S. If approved. This agreement will allow our Colabeam comprised of 12 sales representatives to leverage their demonstrated capabilities and leadership position to deliver an innovative new treatment option for patients living with PFIC. They will also simultaneously strengthen existing relationship with pediatric hepatologists and gain current launch experience to apply to future launches from our pipeline. Throughout 2021, we plan to focus our efforts on preparing the organization to leverage our success.

The deep experience of our teams and our established infrastructure to effectively launch and deliver Sparsentan next year if approved. We look forward to sharing more with you about our progress in the coming quarters. I'd like to turn the call over to Laura now for the financial update. Laura?

Speaker 4

Thank you, Peter. During the fourth quarter, net product sales from our commercial portfolio grew to $51,000,000 a 9% increase over the same period in 2019. For the full year 2020, we reported $198,300,000 in net reported sales. We reported a GAAP net loss of $121,600,000 for the 2020. This includes approximately $97,000,000 of IPR and D expense directly related to the acquisition of CVT-fifty eight in the Orphan Technologies transaction completed in the fourth quarter of last year.

For the full year 2020, GAAP net loss was $169,400,000 The increase over 2019 is largely attributable to higher expenses to support our ongoing clinical and product development efforts as well as the TVT-fifty eight transaction. After adjusting for non cash expenses and income tax, we reported a non GAAP net loss of $112,900,000 for the fourth quarter and $137,000,000 for the full year 2020. On a GAAP basis, R and D expenses were $38,400,000 for the fourth quarter and $131,800,000 for the full year 2020. The decrease compared to 2019 is largely attributable to the discontinuation of the fosmetpantotenate development program in the 2019. On an adjusted basis, R and D expenses were $35,700,000 for the fourth quarter and $121,200,000 for the full year 2020.

Relevant non cash expenses for the fourth quarter included 2,700,000.0 On a GAAP basis, selling, general and administrative expenses for the fourth quarter were $35,700,000 and $135,800,000 for the full year The increase over the same period in 2019 is largely attributable to increased compensation expense to support the growth of our organization and higher professional fees. On an adjusted basis, SG and A expenses for the fourth quarter were 25,500,000 and $98,200,000 for the full year 2020. Significant non cash adjustments for the quarter consisted of $10,200,000 in stock based compensation and depreciation and amortization. As we look ahead to 2021, we anticipate that operating expenses will increase quarter over quarter and year over year as our two pivotal studies of sparsentan continue to advance to the EGFR confirmatory endpoints in 2023 and as we continue to develop PVT-fifty eight. We will also be investing this year to further prepare for two potential launches of sparsentan in 2022 if approved.

Our financial foundation to support this activity remains strong. We ended the year with $361,600,000 in cash and cash equivalents. In February, we completed a common stock offering that resulted in net proceeds of approximately $189,000,000 which is not yet reflected in the balance sheet as of the end of the year. Notwithstanding additional business development, this total cash balance is expected to support our operations beyond the next two years. This includes the ongoing Phase three studies in FSGS and IgA nephropathy as well as plans for the anticipated launch of Parsentan in FSGS next year and the TVT-fifty eight development program.

I will now hand the call back over to Eric for his closing comments. Eric?

Speaker 2

Excellent. Thank you, Laura. And happy birthday, Laura. What a way to spend your day today with us. 2020 was a year of excellent execution for Trevere.

I would like to thank each and every one of our team members and partners for their contributions and for their continued dedication to our common goal of elevating science and service for patients living with rare disease. Their efforts have shown how when we come together with a clear focus on our objectives, that we can be incredibly successful in achieving our goals for patients even in the face of a global pandemic. We are carrying the same dedication and purpose into 2021. In this new year, we will focus on continuing our positive momentum in the sparsentan programs through upcoming regulatory interactions and continued high quality study conduct. We will also focus on further strengthening our commercialization capabilities so that we can effectively meet the diverse needs of patients living with FSGS and IgA nephropathy if sparsentan is approved.

And we will continue to focus on advancing programs such as TBT058 to build our sustainable growth as a leader in the rare disease community. With that, let me turn the call back over to Chris for Q and A. Chris?

Speaker 1

Great. Thank you, Eric. Katrina, can we please go ahead and open up the lines for Q

Speaker 0

Your first question and comes from the line of Greg Harrison of Bank of America. Your line is open.

Speaker 5

Hey, guys. Congrats on the progress and thanks for taking our question. As you approach the potential launch of sparsentan, how are you thinking about leveraging your existing commercial infrastructure? And then what investments beyond your current infrastructure would you need to make to launch the product and then also to educate physicians about the availability of a new treatment for FSGS and potentially IgA nephropathy also?

Speaker 2

Hi, Greg. Thank you very much for the question. And, before I turn it over to Peter for his thoughts on our preparation for the launch, I think one of the unique aspects of Trevere is the infrastructure that we already have with our commercial portfolio, including for physicians that serve the cystinuria community and treat with Thiola, Thiola EC. So many of them are nephrologists. And we have a strong, set of relationships already with many nephrologists in The U.

S. Peter, do want to talk a little bit more about how we would look to expand and what that investment profile would look like for the launch?

Speaker 3

Yes, absolutely, Eric. And thanks, Greg, for your question. Yes, to your point, so we have a field force of two teams. We have a nephrology, urology team and then we have the more ultra rare hepatology team. So currently, we are calling on about 2,000 nephrologists already.

So I think we have a good footprint in nephrology there. We will certainly be expanding that in preparation for the sparsentan launch. I think we have a solid footprint that we can build upon. With regards to how we think about the market education, I think that was the second part of your question. We are planning disease state education.

And I don't know, Noah, if you want to give some color on that with regard to medical affairs initiatives. Yes.

Speaker 2

Thank you, Peter, and Greg. So the way we approach medical education, especially important this year in the prelaunch year, is just to make sure that there's a clear understanding with physicians in the link between proteinuria and eGFR in overall outcomes. I think that's an area that we've pointed to. There's quite a bit of literature on that, and that's clearly being borne out in our data set. So that'll be really one important area.

The other area I think that we're focused on is real world evidence and generating and building that data set and ensuring that we've got the right both global and regional data sets to help ensure that the right data is out there and people's questions are addressed with regard again to the linkedin proteinuria and outcomes and overall understanding of FSGS progression and how devastating this disease really is.

Speaker 5

Thanks. That's very helpful.

Speaker 0

Next question is from Carter Gould from Barclays. Your line is open.

Speaker 6

Great. Good afternoon guys and congrats on all the progress. I guess the first one, just as we think about those conversations with FDA, can you maybe just give us a rough idea on how you tend to communicate the outcomes of those meetings if you'll wait for minutes and if we should expect that I guess, you know, I guess to be communicated by a press release. And then, on the SPARTAN study, we haven't really talked much about that in the past. Just kind of how you see that, you know, I guess what you intend to learn from that and, if we should expect any other sort of additional LCM plans to pop up over the course of the year?

Thank you.

Speaker 2

Sure. Thank you, Carter for the questions. Let me take the first one with regard to the FDA engagement or communication plan. We do have obviously very important meetings with regulators coming up. And our focus would be to communicate after we receive minutes to ensure full alignment and clarity from the FDA.

And so you can expect that in the first half of this year and further updates as they progress towards our submission that is planned in the second half of this year. Noah, would you like to talk a little bit about the SPARTAN study, the status, and really why that study is being conducted? That's a great question. So when you look at PROTECT in an IGAN population, we've got a study, a large study that's going to give us really answer an important question about proteinuria reduction in that population and understand again that linked to EGFR that we've talked about. I think what SPARTAN does layers on there, it's also an eye gain population.

It's a partnership with Lester, with Doctor. John Barrett, who as you know is a luminary in this field. And what the SPARTAN study does, it helps us understand the why. Why are these changes happening? What are the mechanistic changes that are occurring at a cellular level that are leading to these improvements in proteinuria and stabilization of EGFR?

So in SPARTAN, it's a small study, but it's very densely packed with imaging, multiple biopsies. It's really a rare opportunity to look at serial biopsy patients, see what the physiologic changes are on an anatomic level. We've talked about the effects of sparsentan on inflammation. We've seen that in animal models. We've seen improvements in apoptosis, mesangial hypertrophy.

These are the kinds of things that we'd like to be able to show and see in those serial measures. And again, also MRI, real MRI, very robust measures of anatomy, physiology and how the function of the drug is working. So I think it will be important to fill those blanks in. And it's a really great partnership we're very proud of and thrilled to be part of it.

Speaker 1

Thank you.

Speaker 0

Your next question is from Joseph Schwartz from SVB Leerink. Your line is open.

Speaker 7

Hi, thanks very much. I was wondering given your success so far in the primary FSGS, what your latest thoughts were on whether you would have a sense of when the right time to study secondary FSGS, if at all, is? Thank you.

Speaker 2

Joe, thanks for the question. I would say, first and foremost, our priority is to complete the programs that we have so far. And we certainly recognize the broader utility or the potential broader utility of our sense. Maybe Noah can share a little bit about his thoughts and maybe some of the feedback from the nephrology community. Yeah, it's an excellent question.

It really speaks to the common pathway, right, across these disease states, that we've talked about. You know, if you look across multiple disease states, you'll see that ERAs have shown on top of, RAS inhibition to improve proteinuria, stable CFR, and even improve outcomes in some diseases. So I think it really speaks to that. I think that's, secondary FSGS is an area that we've looked at. We've been asked about it quite a bit.

We will have, you know, pretty robust access programs. And we're going to look at that obviously very carefully. To Eric's point, our primary focus is to ensure that DUPLEX is completed and it's done with high quality. And if we get that study finished, but I think we've looked at some other mechanisms. Some of the other opportunities are things like investigator sponsored trials, different ways that we can look at this.

But clearly, there's a demand, there's an interest. I think with secondary FSGS, it's important to treat the underlying risk factors. But what's very interesting is secondary many patients with hepatitis have hypertension. So there's quite a bit of overlap there as well. And there's no reason we wouldn't believe that, this drug wouldn't offer potential benefit.

It's just a matter of, to Eric's point, the timing and when we want to generate that data set.

Speaker 7

Right. Yes, that makes sense. And then another one on sparsentan. I was intrigued by some comments recently that it's highly protein bound and so patients with IgA nephropathy may not need as high a dose as those with FSGS. I was just wondering is there if you could expand on that hypothesis a little bit and tell us what you know, or believe, will be the case with that, phenomenon in terms of, anything that's known as far as like PKPD or any other inferences you can make in that regard?

Speaker 2

Certainly Joe. Why don't, Bill you take that question?

Speaker 8

Certainly. With FSGS and IgA nephropathy one of the key differences between the two is just the frank level of proteinuria. With the wasting of proteinuria being greater in the FSGS patients, We can observe in some patients an albuminuria where they're actually losing enough protein that the albumin level goes down in plasma. And that was one of the rationales, one of the driving rationales behind using the eight hundred milligram dose, the FSG to provide additional drug to offset any that was lost, being bound to protein that's been deposited in urine. From a PKPD standpoint, a lot of, exposure response, data with sparsentan at two hundred, four hundred, and eight hundred milligrams.

And while one hundred and eight hundred are different numerically, when we look at the exposure and the PK values, there's a high degree of overlap. So the difference between the two is not large and they are significantly overlapping. It's just the 800 provides an additional buffer for those patients who might be in an albuminuric state.

Speaker 7

Right. Yes, okay. That helps connect some dots. Thank you for taking my questions. Sure.

Speaker 2

Thank you, Joe.

Speaker 0

Your next question comes from Tim Lugo from William Blair. Your line is open.

Speaker 9

Hi, guys. This is John on for Tim. Thanks for taking my question. I wanted to say congrats on the recent collaboration with Albireo. We know Ron and the rest of the team over there really well and think that they're going be a really great partner.

I just wanted to get some of your thoughts on your expectations for odevixibat. And as a follow-up housekeeping question, how we should think about incorporating the deal into our models? Thanks.

Speaker 2

Thank you, John, for that. We're really pleased to have the collaboration. And, you know, in rare disease, collaboration is such a critical part of reaching these patients who are so often underserved. I'll ask Peter to talk a little bit about our thoughts. And we'll obviously need to be very careful and limit our thoughts on the broader opportunity.

And I think really rely on Ron and his team to provide that. But I think we can talk about strategically where we see this opportunity sitting for us. Peter?

Speaker 3

Yes. Thanks, Eric. And it's indeed a great question. I'm really very pleased with the collaboration opportunity with Alberio. And I think to Eric's point, I mean, we see mainly the strategic value for us.

I think this collaboration demonstrates and further strengthens our leadership position in the rare hepatology field. But thinking about our pipeline and the products that we are planning to launch in the next few years, I think it's a great opportunity as well for us to further sharpen our experience of launching new products in the field, new molecular entity, which is helpful for us for sparsentan next year if approved, but also for our CTX indications for Chenodal and later on TBT058. So I think it's an important capability, in particular when you think about the COVID in the post COVID environment that we are playing in. And so I think this collaboration also allows us continued access to our core stakeholders in the hepatology community.

Speaker 9

That's very helpful. Thank you.

Speaker 0

Your next question is from Michelle Gosson of Canaccord Genuity. Your line is open. Hi. Thanks for taking my question. I'm just wondering if you've had any preliminary payer discussions and, if you could maybe comment on how strong your value proposition might be for sparsentan and FSGS with just proteinuria data?

Or would you expect, I guess, that immature eGFR data that we've talked about previously to be in a future label? I guess that's two questions. And then do you anticipate the value proposition would change between the interim proteinuria results and a potential, I guess, accelerated approval to, you know, having full confirmatory eGFR data?

Speaker 2

Michelle, thanks so much for the questions. And certainly very important as part of the work that Peter and Noah and their teams are doing to prepare for commercialization. I think the answer is clearly yes. There have been ongoing discussions with payers, both in The U. S.

And Europe, to make sure that we understand with this emerging rare renal field, how do we ensure that we have a strong value proposition for access and reimbursement for what we see as the addressable population. Peter, why don't you talk a little bit about how we see value proposition and the role that proteinuria would play in that assessment?

Speaker 3

Yeah, absolutely. And thanks for your question, Michelle. Very good question and very important to make sure that the value of sparsentan and how that translates in the longer term is well characterized. I think that value comes from several components. I mean at the R and D Day in December, we spoke about like the innovative mode of action of sparse symptom, the ability to delay towards end stage kidney disease.

But we also talked about quality of life and how we integrate quality of life in our modeling. And then you have the safety component perspective like steroid sparing proposition potentially. So just referring to our R and D Day, don't know if you remember Doctor. Barrett was showing some of his analysis on patient level data where he showed like a thirty percent reduction in proteinuria actually translated into a ten point four year delay towards end stage kidney disease. So we are doing the same work right now for FSGS.

So we will have that translated value based on historical data, but then also translating it to patient level data directly in physician offices. So that's how we are approaching the value proposition. We have, to Eric's point, continuing dialogue with payers. And, yes, that's how we plan for the pricing discussion.

Speaker 0

Okay. Thank you guys for taking my question.

Speaker 2

Thank you, Michelle.

Speaker 0

Your next question comes from the line of Maury Raycroft of Jefferies. Your line is open.

Speaker 7

Hi, everyone. Congrats on the progress and thanks for taking my questions. First one, I just wanted to check-in on an update that happened post close with FibroGen. They got a request from FDA for an AdCom. I think it was unexpected based on what FibroGen has said in the past.

So just wondering what your thoughts are on the unexpected update and if you could comment on whether you've interacted with FDA recently and how did those interactions go?

Speaker 2

Maury, thank you very much for the questions. I've not seen any details specifically on FibroGen and wouldn't see our place to comment on any detail about their program. What I can say is that we've had and continue to have discussions with FDA. I'll have Bill share a little bit about our plans and how his team is preparing for the submission and review.

Speaker 8

Certainly. We have a pre NDA meeting coming up in the first half of the year. It will be the agency's first opportunity to look at, evaluate the interim data in detail. And overall the objective of the meeting for us in that sense will be to align on all plans to serve these data for Subpart H accelerated approval. We'll be looking to align on how we present the data, the current study as well as all the legacy data and make sure that it suits their need for review.

At that point there may or may not be a discussion about panels to your question. And once we've had that meeting and then and have minutes we as Eric stated earlier, we'll communicate that out to the public.

Speaker 7

Great. That's really helpful. Okay. Well, thanks for taking my questions.

Speaker 2

Thank you, Maury.

Speaker 0

Your next question comes from the line of Lisa Bagel from Evercore ISI. Your line is open.

Speaker 10

Hi there. Thanks for taking the question.

Speaker 4

Can you maybe just speak

Speaker 10

to now that you've had time to reflect on the data a little bit more, sort of the change in placebo, well not change, but we had about a 9% placebo rate in the Phase two. And then it went up to twenty six percent in this study, which actually was kind of close to, in a way, what the original data was for sparsentan in the first study. So anyway, just curious on kind of your thinking of and stop placebo, sorry, irbesartan. Why do we see that kind of gap up there? I have my own thoughts, but curious on if you've had any chance to think about that.

And then any other feedback you've gotten on the data so far would be helpful. Thank you.

Speaker 2

Lisa, thanks for the questions. And I'll ask Noah to share his thoughts and perhaps some of the discussions with nephrologists around the FPRE data that we've seen. But I think before, I turn it over to Noah, I'd say, first and foremost, you know, the results that we saw at thirty six weeks were incredibly strong. And support our belief that we have the data, one that's within our powering, but two, sufficient for treatment effects for Subpart H. I'll ask Noah to share a little bit about his thoughts on why we might have seen that.

But I think certainly, we're contributing a tremendous amount to the field in this being the largest and the longest trial conducted within FSGS. So very little information previously to go on beyond the eight weeks that we had in our Phase II. Noah? Yes. I think to that point, Eric, and to Lisa's question, if you look at the data that you're referencing, Lisa, at eight weeks where we had the double blind period for the Phase II DUET study, we saw a nine percent versus twenty eight percent achievement of FPRE.

So that was at eight weeks. What we didn't know was how that would progress out to thirty six weeks. And now in DUPLEX, we've got the thirty six week data. And I just want to take a step back and reflect on something Eric said, which is DUPLEX really is the largest and longest study in FSGS and certainly has provided lots of insight in terms of how not only drugs progressed, but the insights for the field. And in the thirty six week data, DUPLEX showed that sparsentan

Speaker 3

was consistent with

Speaker 2

the expectation of the OLE. So if you go to the thirty six week data point, it almost tracks perfectly to a 42% achievement of FPRE, which really speaks to the remarkable consistency, of the drug. And it outperformed, irbesartan in a statistically significant manner, which tells you that this was within our powering assumptions. And I think we're and when you talk about kind of how we view it and then have validated this with nephrology community and with the inbounds of it, they're incredibly encouraged by, a sixty percent relative likelihood or greater relative likelihood of achieving FPRE, which we know is important clinically meaningful endpoint linked to EGFR stabilization. With and it's important to mention a comparable safety profile between those two groups.

So in a sense, really, this is the strongest proteinuria reduction that has been generated in this field, if you think about it with a non immunosuppressive therapy. And I think that's a critical piece because there's been just a huge need, a huge unmet need for once a day, it's an oral treatment. And I think it's well characterized through our Phase II duet long term data set. We understand fairly well how this drug works from an efficacy standpoint. So I think that's really what has really led to the excitement.

I think the only other thing, Noah, that I would add is that some of the feedback that we've heard from nephrology thought leaders is also that the results are not surprising. And while there was a greater increase, from eight weeks to thirty six weeks, that this is consistent with clinical practice. So I think the consistency that we see between this trial and clinical practice, but as Noah mentioned, the consistency of sparsentan's profile on this endpoint from Phase II to Phase III is incredibly encouraging. And I think that's one of the themes of the feedback that we're hearing from KOLs.

Speaker 10

Okay, thanks. And I know there's the CKD3 conference is coming up later this week. And I noticed you're going to be giving a talk there. Will that include any updates or details on the trial so far, the data, anything like that?

Speaker 2

No, it will not provide any additional data. It will be, you know, an additional presentation of what we know to date and what we have announced publicly to date.

Speaker 10

Okay, great. Thanks. And then just if you could talk a little bit about TBT058. Is this trial is it slightly delayed? I thought we were maybe expecting data earlier in 2021 and then but whenever we get data, if you could just frame up, you know, what we should be looking for and expecting in that data set.

And that's my final question. Thank you.

Speaker 2

Okay. Thanks, Lisa. And, the program continues to, progress. And I'll ask Bill to share a little bit about the status and what we'll be looking for from that trial later this year.

Speaker 8

Certainly. Thanks for the question, Lisa. As Eric said, the study continues to advance and we do expect to have preliminary data this year. From what we want to or expect to see from that we're going to be evaluating the selection of the right dose, or the effect of the medicine across different doses looking primarily at reductions in plasma homocysteine. And additionally we're going be working to develop a regulatory strategy going forward.

I think some of the caution that you're hearing in our language is just that with a smaller study the potential for impact I think is greater than in something like DUPLEX with sites in different regions. Additionally, in this case we have a biologic as opposed to a small molecule. And the contract manufacturing space in the biologic world, is impacted right now quite broadly with COVID vaccine manufacturer. And while we have contingency plans in place and we are on track it's an area that we continue to monitor.

Speaker 10

Okay. Thank you.

Speaker 5

Thanks, Lisa.

Speaker 0

Your next question comes from the line of Laura Chico from Wedbush Securities. Your line is open.

Speaker 11

Thanks very much for taking the question. I just wanted to circle back on one to clarify, and that's with respect to the protein binding. So of sparsentan, I think you mentioned earlier that dosing in FSGS trial is permitted to go up to eight hundred milligrams, excuse me, but in PROTECT you're only dosing up to four hundred milligrams. In terms of clarifying I just wanted to make sure I understood was the decision to use the lower dose in PROTECT versus DUPLEX purely based on the drug's protein binding properties? Or are there other factors that kind of came into the decision making process there?

And then perhaps one quick follow-up question for Laura perhaps and happy birthday. While we have the DUPLEX top line results in hand, obviously the study is going to be continuing. And just wondering how we should be thinking about the cadence of spend on the R and D line this year with two pivotal studies continuing? Thanks very much.

Speaker 2

Thanks, Laura. Maybe I'll mention very briefly about the protein binding and ask Bill to provide anything that I've missed. I think one of the other aspects that came into play is from the DUET study, albeit that is in FSGS. We do see that both doses of four hundred and hundred are quite effective in proteinuria reduction. And, you know, we believe that we would not be compromising much efficacy.

And I think as Bill alluded to, you know, the dose response is more sigmoidal. And at four hundred you're getting close to the top of that S curve. And so, you know, that was a very important component of some of the decision making about what dose to select. So yes, it was about protein binding and serum protein levels. But it was also about the degree of efficacy conferred at those doses.

Bill, anything further that you'd want to add on that?

Speaker 8

No, I think that's exactly right, Eric.

Speaker 2

Okay. And Laura?

Speaker 4

Yeah. Hi, Laura. Thanks for the birthday wishes. You can expect to see R and D expenses increase over the current quarter level for a lot of the reasons we've been describing. I mean think about maybe more traditional Phase III where once the studies readout your R and D expenses could technically start to trend downward.

In our case with the Subpart H pathway we still have to run the studies out to the full one hundred and eight week confirmatory EGFR endpoint. In addition to that we'll be investing in our new program, TBT058 and also building up for commercial scale with our supply chain. So those are significant investments that we'll all be happy to take at the same time. So definitely expect some modest increases in R and D as we go quarter over quarter compared to current levels.

Speaker 11

Thanks very much.

Speaker 2

Thank you, Laura.

Speaker 0

I am showing no further questions at this time. I would now like to turn the conference back to Mr. Chris Klein.

Speaker 1

Great. Thank you, Katrina. Thank you, everyone, for joining us this afternoon to talk about our many accomplishments in 2020 and our exciting outlook for 2021. This concludes our call for today. We look forward to providing you updates in the near future.

I hope you all have a great rest of the week.

Speaker 0

Ladies and gentlemen, this concludes today's conference. Thank you for your participation, and have a wonderful day. You may all disconnect.