Q4 2021 Travere Therapeutics Inc Earnings Call
[music].
Good day, Thank you for standing by and welcome to <unk> Therapeutics fourth quarter and full year 2021 financial results and corporate updates at this time all participants lines are in a listen only mode. After the speaker's presentation, there will be a question and answer session.
Operator: Good day. Thank you for standing by. Welcome to Travere Therapeutics fourth quarter and full year 2021 financial results and corporate update. At this time, all participants line are in a listen-only mode.
Operator: After the speaker's presentation, there will be a question and answer session. To ask a question during this session, you will need to press star 1 on your telephone. Please be advised that today's conference is being recorded. If you require any further assistance, please press star 0.
Ask a question during this session you will need to breath star one on your telephone please.
Please be advised that today's conference is being recorded.
Operator: I would now like to hand the conference over to your speaker today, Mr. Chris Cline. Thank you. Please go ahead.
If you require any further assistance please press star zero.
I'd now like to hand, the conference over to your Speaker today, Mr. Chris Cline. Thank you. Please go ahead.
Thank you, Brian and good afternoon, and welcome to the <unk> Therapeutics fourth quarter and full year 2021 financial results and corporate update call. Thank you all for joining US today's call will be led by our Chief Executive Officer, Dr. Eric Dube, Eric will be joined for the prepared remarks by Dr. Julie <unk>, Our Chief Medical Officer, Peter Herma, Our Chief commercial officer, and our Chief Finance.
Christopher Cline: Thank you, Bojana. Good afternoon, and welcome to Travere Therapeutics fourth quarter and full year 2021 financial results and corporate update call. Thank you all for joining us. Today's call will be led by our Chief Executive Officer, Dr. Eric Dube. Eric will be joined for the prepared remarks by Dr. Jula Inrig, our Chief Medical Officer, Peter Heerma, our Chief Commercial Officer, and our Chief Financial Officer, Laura Klag. Dr. Bill Rote, Senior Vice President of Research, will join us for the Q&A session.
Officer, Laura Clague, Dr. Bill Rote senior Vice President of research.
Join us for the Q&A session.
Christopher Cline: Before we begin, I'd like to remind everyone that statements made during this call regarding matters that are not historical facts are forward-looking statements within the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements are not guarantees of performance. They involve known and unknown risks, uncertainties, and assumptions that may cause actual results, performance, and achievements to differ materially from those expressed or implied by the statement.
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 state.
Please see the forward looking statement disclaimer on the company's press release issued earlier today as well as the risk factors section in our forms 10-Q, and 10-K filed with the SEC. In addition, any forward looking statements represent our view only as of the date such statements are made February 24 2022.
Christopher Cline: Please see the forward-looking statement disclaimer on the company's press release issued earlier today, as well as the risk factors section in our Forms 10-Q and 10-K file at the SEC. In addition, any forward-looking statements represent our view only as of the date such statements are made, February 24, 2022. Interviewers specifically disclaim any obligation to update such statements to reflect future information, events, or circumstances. Let me now turn the call over to Eric. Eric?
<unk>, specifically disclaims any obligation to update such statements to reflect future information events or circumstances.
Now I'll turn the call over to Eric Eric.
Thank you, Chris and good afternoon, everyone 2021 was an outstanding year for Turkey, or our pipeline of potential first in class rare disease treatments delivered three positive topline readouts from our ongoing study.
Eric Dube: Thank you, Chris. And good afternoon, everyone. 2021 was an outstanding year for Travere.
Eric Dube: Our pipeline of potential first-in-class rare disease treatment delivers three positive top-line readouts from our ongoing study. We made significant regulatory progress and established pathways to potential accelerated approvals for our lead candidates for our sentence in both IG nephropathy and focal segmental glomerular sclerosis or FSGS. We delivered 6% growth in net product sales from our commercial products, despite the ongoing challenges from COVID and a generic entrant for Thiola, and we continue to strengthen our ability to successfully deliver our treatments to the rare disease community in the future. I'll touch on each of these areas briefly.
Significant regulatory progress and established pathways to potential accelerated approvals.
Our lead candidates for center in both Iga nephropathy, and focal segmental glomerular sclerosis, or <unk>, yes, we.
We delivered 6% growth in net product sales from our commercial products. Despite the ongoing challenges from Covid and the generic entrant for firewall.
And we continued to strengthen our ability to successfully deliver our treatment for the rare disease community in the future I'll touch on each of these areas briefly.
Eric Dube: First, regarding the pipeline, we are incredibly pleased with the outcomes from both of our Phase 3 studies of Sparsentin, Duplex in FSGS and Protect in IJ nephropathy. With positive top-line interim readouts from both studies, Sparsensen has established a robust body of evidence around its ability to reduce proteinuria in patients with rare kidney diseases. Importantly, the sparse sentence readouts have positioned us for three potential regulatory submissions this year.
First regarding the pipeline we are incredibly pleased with the outcomes from both of our phase III studies, thus far centered duplex in SSG.
And protect and Iga nephropathy.
With positive top line interim Readouts from both studies <unk> has established a robust body of evidence around its ability to reduce proteinuria and patients with rare kidney diseases.
Importantly, the <unk> readouts have positioned us for three potential regulatory submissions this year.
Eric Dube: I am pleased to report that we remain on track to submit an application for accelerated approval under subpart H for IGA necropathy during this quarter. If that application is accepted and granted priority review, we would anticipate a PDUFA date for sparsentine and IgA nepropathy towards the end of this year. We are also on track to submit to the FDA additional EGFR data from the ongoing duplex study in the first half of this year.
I am pleased to report that we remain on track to submit an application for accelerated approval under sub part H for Iga nephropathy during this quarter.
If that application is accepted and granted priority review, we would anticipate a <unk> date for <unk> in Iga nephropathy towards the end of this year.
We are also on track to submit to the FDA additional egfr data from the ongoing duplex study in the first half of this year.
Eric Dube: If at that time, the data further strengthen the prediction of long-term benefits in the study as we should expect they should, we anticipate submitting an NDA for accelerated approval for FSGS around the middle of this year. Together with our European partner, V4 Pharma, we also remain on track to submit a combined IgA nephropathy and FSGS MAA submission for conditional approval for farcentin in Europe, pending additional support of eGFR data from Duplex. As you can see, we have a very exciting year ahead for Sparsanta.
If at that time the data further strengthen the prediction of long term benefits in the study as we should expect to pay should we anticipate submitting an NDA for accelerated approval for <unk> around the middle of this year.
Together with our European partner <unk> Pharma, we also remain on track to submit a combined Iga nephropathy and <unk> <unk>.
A submission for conditional approval for <unk> in Europe .
Pending additional support of Egfr data from duplex.
As you can see we have a very exciting year ahead for sports Center.
Eric Dube: Also from the pipeline, in December, we reported positive top-line data from the ongoing Phase I-II Composed Study of pegdobatinase in classical homocystinuria, or HCU, a rare and devastating metabolic disorder. We believe these data support the potential for pegtobatinase to become the first therapy targeting the underlying cause of HCU for the more than 7,000 people in the U.S. and Europe who are not able to adequately control their HCU with the available treatment options today.
Also from the pipeline in December we reported positive topline data from the ongoing phase one two composed study a pegged about Nate and classical home assistant urea or <unk>, a rare and devastating metabolic disorder.
We believe these data support the potential for pegged about needs to become the first therapy targeting the underlying cause of HCA for the more than 7000 people in the U S and Europe , who are not able to adequately controlled our HCA you with the available treatment options today.
Eric Dube: Having achieved this milestone also reinforces confidence in our strategy of bringing in external programs to further address the unmet needs of rare disease patients while diversifying and building our growth potential. This year, we look forward to engaging with regulators to establish next steps for a pivotal development program while we also gain experience with formulation enhancements and further explore the dose response curve in the final plan cohort of the study. On the commercial side of the business, we continued our track record of strong execution.
Having achieved this milestone also reinforces confidence in our strategy of bringing in external programs to.
Further address the unmet needs of rare disease patients, while diversifying and building our growth potential.
This year, we look forward to engaging with regulators to establish next steps for a pivotal development program. While we also gained experience with formulation enhancements and further explore the dose response curve and the final planned cohort of the study.
On the commercial side of the business, we continued our track record of strong execution.
Eric Dube: Our results in 2021 marked the sixth straight year of organic growth. We believe this illustrates the strength of our commercial capabilities and our ability to identify, treat, and support patients living with rare kidney and liver conditions. For 2022, we currently expect to see continued growth of our bioasset product. But we do expect pressure on the fiola business. As a result, our consecutive growth streaks... And total net product sales is not likely to continue this year.
Our results in 2021 marked the sixth straight year of organic growth.
We believe this illustrates the strength of our commercial capabilities and our ability to identify and support patients living with rare kidney and liver condition.
For 2022, we currently expect to see continued growth of our bile acid products, but we do expect pressure on the <unk> business as a result, our consecutive growth Street.
In total net product sales is not likely to continue this year.
Eric Dube: But with the potential for Sparsentine to launch as early as the end of this year, we look forward to returning to growth again in the future. Importantly, our business planning has been accounting for this. Peter and his team are continuing to build upon our commercial strengths to translate our experience and establish relationships for successful launches in the U.S. Finally, I'd like to introduce Dr. Jula Inrig, our new Chief Medical Officer. Jula joined us in January and has taken over for NOAA following his planned transition.
But with the potential for <unk> to launch as early as the end of this year, we look forward to returning to growth again in the future.
Importantly, our business planning has been accounting for this.
Peter and his team are continuing to build upon our commercial strength to translate our experience and established relationships.
Our successful launches of <unk> in the U S.
Finally, I'd like to introduce Dr. Julie <unk>, our new Chief Medical Officer, Julian joined US in January and has taken over for Noah following his plant transition Julian.
Eric Dube: Jula is a nephrologist who brings to Travere more than 15 years of expertise in drug development, clinical trial planning and execution, global regulatory engagement, and medical oversight. She has a clear passion for championing positive change for patients and a deep history of advancing new treatment options for rare diseases, specifically in rare nephrology. She joins our team at an exciting time as we approach the next inflection point on the path to bringing innovation to patients living with IgA nephropathy and FSGS. With that, let me turn the call over to Jula for the clinical update. Thank you, Eric, and good afternoon.
The nephrologists to brings to <unk> more than 15 years of expertise in drug development.
Clinical trial planning and execution global regulatory engagement and medical oversight.
She has a clear passion for champion a positive change for patients and a deep history of advancing new treatment options for rare diseases, specifically in rare nephrology.
Joins our team at an exciting time as we approach the next inflection point on the path to bringing innovation to patients living with Iga nephropathy, and <unk> with that let me turn the call over to Julie for the clinical update July .
Thank you Eric and good afternoon.
Jula Inrig: I'm honored to be here and partnering with our team members at Travere to advance new therapies for people living with rare, Over the course of my career, I've experienced the challenges that patients and their families have encountered as a result of having few options. Available to Slow the Progression of Their Kidney Disorders Toward End, That has shaped my own personal mission to help the nephrology field advance new treatments that may be able to delay the time to transplant or dialysis.
Honored to be here and partnering with our team members at <unk> to advance new therapies for people living with rare disease.
Over the course of my career I've experienced the challenges that patients and their families have encountered as a result of having few options available to slow the progression of their kidney disorders towards end stage kidney disease.
That is my own personal mission to help the nephrology field advance new treatments that may be able to delay the time to transplant or dialysis.
Jula Inrig: This has taken the form of working with FDA, EMA, and community leaders to further establish proteinuria as an acceptable regulatory endpoint for clinical trials in nephrology, and it has taken the form of helping strategize and execute nearly 50 clinical trials in the space. I was incredibly motivated to join the Travere team because of the patient-inspired leadership that has been established over the last several years, and the exciting potential to continue working at the forefront of advancements in rare nephrology. Ultimately, by helping physicians understand the foundational role our suntan may be able to play for their patients, if necessary. To that end, I am pleased with the continued progression of the Sparse Unchanned program.
This is taking the form of working with FDA EMA and community leaders to further establish proteinuria as an acceptable regulatory endpoint for clinical trials in nephrology.
And it has taken the form of helping strategize and execute nearly 50 clinical trials in this space.
I was incredibly motivated to join the <unk> team because of the patient inspired leadership that has been established over the last several years.
The exciting potential to continue working at the forefront of advancements in rare nephrology Ulta.
Ultimately by helping physicians understand the foundational role suntan may be able to play for their patients if approved.
To that end I am pleased with the continued progression of the score content programs.
Jula Inrig: Both the duplex study in FSGS and the PROTECT study in IJ nephropathy are progressing according to expectations and are well positioned for their confirmatory eGFR endpoint readouts next year. At this date, Sparsantan has consistently shown the ability to meaningfully reduce proteinuria versus the current standard of care. Protonuria is a key measure by which nephrologists determine treatment for patients with protonuric, In the Combined Treatment Group in the Phase II Duet Study in FSGS, sparsentan more than doubled the reduction of proteinuria compared to the active control herbicartin.
Both the duplex study in FCS and the protect study in Iga nephropathy are progressing according to expectations and are well positioned for their confirmatory Egfr endpoint readout next year.
To date <unk>.
Has consistently shown the ability to meaningfully reduce proteinuria versus the current standard of care.
Proteinuria is a key measure by which nephrologist determined treatment for patients with kidney diseases.
And the combined treatment group and the phase two duet study in Fcs.
<unk> more than doubled the reduction of proteinuria compared to the active control irbesartan.
Jula Inrig: In the top-line interim results from the Phase III duplex study in FSGS, treatment with Barsentan resulted in a 60% greater relative likelihood of achieving the clinically relevant FSGS partial remission of proteinuria endpoint, or FPRE, when compared to the active control herbicartin, and in the Phase 3 PROTECT Study in I.J.
And the top line interim results from the Phase III duplex study in <unk>.
Treatment with <unk> resulted in a 60% greater relative likelihood of achieving that clinically relevant SGS partial remission of proteinuria endpoint or CRE when compare to the active control irbesartan.
And in the phase III protect study in Iga nephropathy.
Jula Inrig: Sparsantan demonstrated a greater than three-fold reduction in proteinuria from baseline compared to the active control herbicide. The first time a single non-immunosuppressive therapy demonstrated this magnitude of effect on proteinary reduction in a large, well-controlled study in IgA nephropathy. These results are exciting for the nephrology community and are providing great motivation for our medical team. As Eric outlined earlier, we are on track for all of our regulatory milestones planned for this year. Of note, we were encouraged to see FDA recently grant the first accelerated approval based on proteinary reduction in IgA nephropathy. This precedent is in clear alignment with our approach.
<unk> demonstrated a greater than threefold reduction in proteinuria from baseline compared to the active control irbesartan.
The first time, a single non immunosuppressive therapy demonstrated this magnitude of effect on proteinuria reduction and a large well controlled study in Iga nephropathy.
These results are exciting for then for allergy community and are providing great motivation for our medical team.
As Eric outlined earlier, we are on track for all of our regulatory milestones planned for this year.
Jula Inrig: For IGN Neuropathy, we anticipate submitting our application for accelerated approval in the U.S, for the end of this quarter. We would anticipate hearing a response on that application in the second quarter with a potential PDUVA date as early as the fourth quarter, if accepted for priority. And for FSGS, we are on track to provide the FDA with additional EGFR data from the ongoing duplex study in the first half of this year.
Of note we were encouraged that the FDA recently granted accelerated approval based on preliminary reduction.
<unk> nephropathy.
This precedent in clear alignment with our approach.
For Iga nephropathy, we anticipate submitting our application for accelerated approval in the U S. Before the end of this quarter.
We would anticipate carrying a response on that application in the second quarter with a potential <unk> date as early as the fourth quarter if accepted for priority review.
And breakfast, yes, we're on track to provide the FDA with additional Egfr data from the ongoing duplex study in the first half of this year.
As many of you will recall at the time of the interim assessment for duplex a high proportion of the available Egfr data weighted to early study visits.
Jula Inrig: As many of you will recall, at the time of the interim assessment for duplex, a high proportion of the available EGFR data were weighted to early study visits, and this is the period in which acute reductions in EGFR are likely to be most prominent from RAS and ETA blockages.
This is a period in which the acute reductions in egfr are likely to be most prominent from RAF and ETE blockade.
Following our pre NDA interactions for FX, just last year, we aligned with the FDA on our plan to provide the agency with additional Egfr data from the ongoing duplex study to provide a more mature dataset and enable us to continue on the accelerated approval pathway for our first yes.
Jula Inrig: Following our pre-NDA interactions for FSTS last year, we aligned with the FDA on a plan to provide the agency with additional EGFR data from the ongoing duplex study to provide a more mature data set and enable us to continue on the accelerated approval pathway for FSTS. At the time of the planned EGFR data cut later this year, all patients in the duplex study will have completed at least one year of treatment, and approximately 50% of patients will have completed two years of treatment. Based upon our understanding of Sparsantan and its mechanism of action, We believe at this time point in the duplex study, the data will have sufficiently matured to strengthen the prediction for long-term EGFR benefits.
At the time of the plant Egfr data cut later this year all patients in the duplex study will have completed at least one year of treatment and approximately 50% of patients will have completed two years of treatment.
Based upon our understanding of our Phantom and its mechanism of action. We believe at this time point and the duplex study the data will have sufficiently matured to strengthen the prediction for long term Egfr benefit.
If the Egfr data continued to progress as planned we expect to submit for accelerated approval in the U S. Mid this year.
Jula Inrig: If the EGFR data continue to progress as planned, we expect to submit for accelerated approval in the U.S. mid this year. Finally, I'll touch on our PEG-to-Batinase program, which reported positive top-line results from the ongoing Phase I-II Composed Study in December. From a safety perspective, we were pleased to see that PEG-to-batonase has been generally well tolerated to date in the study. From an efficacy perspective, pectobatinase demonstrated dose-dependent reductions in total homocysteine during the 12 weeks of treatment.
Finally, I will touch on our <unk> program, which reported positive top line results from the ongoing phase <unk> study in December .
From a safety perspective, we were pleased to see that <unk> has been generally well tolerated to date in the study.
From an efficacy perspective, <unk> demonstrated dose dependent reductions in total hummel 15 during the 12 weeks of treatment.
Jula Inrig: And we were very pleased to see that in the highest-dosed cohort to date of 1.5 mg per kg, dosed twice weekly. Treatment with pegtobatinase resulted in rapid and sustained reductions in total homocysteine beginning at week 2 and continuing through 12 weeks of treatment. Resulting in a 55.1% reduction from baseline and maintenance of total homocysteine below a clinically meaningful threshold of 100 micrograms. Additionally, the data demonstrated a substantial reduction in methionine and increase in cistathionine in a dose-dependent manner following treatment with PEG-2-batonase, which supports our mechanistic approach.
And we were very pleased to see that in the highest dose cohort to date of one five milligrams per kilogram dose twice weekly treatment with <unk> resulted in rapid and sustained reductions in total Humla 15, beginning at week, two and continuing through 12 weeks of treatment.
Resulting in a 55, 1% reduction from baseline and maintenance of total how much <unk> below a clinically meaningful threshold of 100 micro mills.
Additionally, the data demonstrated a substantial reduction in methionine and increase and just defining in a dose dependent manner following treatment with <unk>, which supports our mechanistic mechanistic approach.
These data provide proof of concept supporting the potential for <unk> to become the first disease modifying therapy for <unk> and give us confidence in moving toward aligning with regulators on a pivotal program.
Jula Inrig: These data provide proof-of-concept, supporting the potential for PEG-tobatenase to become the first disease-modifying therapy for HCU, and give us confidence in moving toward aligning with regulators on a pivotal program. As we do that, the program this year will be focused on three areas. The first is engaging with regulators to align on total homocysteine as a biomarker end point, and with that, a phase three program design that can support approvals in the U.S. and abroad.
Jula Inrig: The second is completing the sixth cohort in the COMPOSE study to further build our knowledge of the dose-treatment response of pectobatinase and to explore potential formulation advances. Enrollment activities here are already underway. The third is working through the global supply constraints suppliers in the industry are currently facing to scale CMC and manufacturing for the pivotal phase of development and commercial action.
As we do that the program this year will be focused on three areas.
The first is engaging with regulators to align on total <unk> as a biomarker endpoint and with that a phase III program design that can support approvals in the U S and abroad.
The second is completing the sixth cohort and the composed study to further build our knowledge of the dose treatment response of peg to that and to explore potential formulation advancements.
<unk> activities here already underway.
The third is working through the global supply constraint suppliers in the industry are currently facing the scale CMC and manufacturing for the pivotal phase of development and commercial access.
Jula Inrig: Overall, I have inherited a great set of programs with real potential to make a meaningful difference in patients' lives, and an extremely talented team to help advance them. We are well positioned to deliver Sparsantan if approved as the first non-immunosuppressive therapy for the treatment of IgA nephropathy and to continue the advancement of our other program systems. Let me now turn the call over to Peter for the commercial update. Peter?
Overall I have inherited a great set of programs with real potential to make a meaningful difference in patients' lives.
And an extremely talented team to help advance them.
We are well positioned to deliver smart suntan if approved as the first not immunosuppressive therapy for the treatment of Iga nephropathy and to continue the advancement of our other programs this year.
Let me now turn the call over to Peter for the commercial update Peter.
Thank you Joe.
Peter Heerma: Thank you, Jula. As Eric touched on earlier, the commercial organization continued to execute incredibly well under challenging conditions in 2021. Despite fewer patients seeing their physicians as a result of COVID and a generic entrance for the original formulation of Viola, we identified and treated new patients with all of our commercial products and achieved our targets for the year, in the fourth quarter. Net product sales grew by 7% This was driven by organic year-over-year growth across CIOLA and the bio-acid product.
It's Eric.
The commercial organization continued to execute incredibly well under challenging conditions in 2021.
Despite fewer patients seeing their physicians as a result of COVID-19 and the generic entrants for the original formulation of <unk>.
Densify and treated <unk> patients with all of our commercial products and achieved our targets for the year.
In the fourth quarter, specifically net product sales grew by 7%.
This was driven by organic year over year growth across iola.
Is it products.
Peter Heerma: We finished the year with approximately $211 million in net product sales, a more than 6% organic increase over 2020. As we look to 2022, we are expecting continued growth of our bioassay products, but increasing pressure on our Sciola business as a result of generic competition. This has been factored into our business planning for some time and allows a natural pivot to our preparation for launching SparCenter. The results from this past year further bolster my confidence in our team's commercial execution and their established relationships in the rare nephrology community. We are building upon this established infrastructure and expertise as we prepare our organization to position Sparsantan as the new treatment standard for IHGN nephropathy, if approved. We are currently doing this by focusing on three areas.
We finished the year with approximately $211 million and net product sales.
More than 6% organic increase over 2020.
As we look to 2022, we are expecting continued growth of our bile acid products.
Increasing pressure on our cellular business as a result of generic competition.
This has been factored into our business planning for some time and allows a natural pivot to our preparation for <unk> syndrome.
The results from this past year further bolster my confidence in our team's commercial execution.
Established relationships in the Rev Nephrology community.
We are building upon this established infrastructure and expertise as we prepare our organization to position <unk> as the new treatment standard for Iga nephropathy.
We are currently doing this by focusing on three areas.
The first is further educating the scientific community by leveraging the deep understanding and long held belief in the utility of proteinuria reduction amongst patrologist.
Peter Heerma: The first is further educating the scientific community by leveraging the deep understanding and long-held belief in the utility of proteinuria reduction amongst nephrologists. And this parcentile, if approved, may substantially lower proteinuria for their patients. We know from syndicated market research that nephrologists consider the emerging product profile of spirocentam as one of the most desirable programs in development.
And this far symptom if approved may substantially lower button yulia for their patients.
We know from syndicated market research that nephrologist consider merging product profile sparse anthem. It's one of the most desirable programs in development. So we are building and educating people that.
Peter Heerma: So we are building and educating upon this. The second is furthering our work to instill a strong understanding of the burden of disease amongst payers. The value that Spar Center may be able to provide and progressing our strategy that will allow for broad access to become a new treatment standard if approved. Many of you will recall the 2019 publication of the Kidney Health Initiative Project Team, where proteinuria was identified as the most widely recognized and well-studied risk factor for the progression to end-stage kidney disease in IgA and pharma.
The second is furthering our work to instill a strong understanding of the burden of disease amongst payers the value that <unk> may be able to provide and progressing our strategy that will allow for broad access to become new treatment standard if approved.
Many of you will recall the 2019 publication of the kidney Health initiative project team.
Proteinuria was identified as the most widely recognized and will studies risk factor for the progression to end stage kidney disease.
Pharmacy.
Following this risk prediction analysis, the patient level risk assessment was presented describing that a 30% reduction you've brought in urea could result in a greater than 10 year delay in dialysis for Iga Iga nephropathy patients.
Peter Heerma: Following this risk prediction analysis, the patient-level risk assessment was presented describing that a 30% reduction in proteinuria could result in a greater than 10-year delay in dialysis for IgA nephropathy patients. With the proteinuria reduction demonstrated in the recent PROTECT data, we have a strong foundation to build upon. Lastly, now that we have line of sight of the regulatory path this year, we have plans to expand our commercial organization for law and trade. This includes adding to our field force to reach monofrogs.
With the proper newly a reduction demonstrated in the recent protect data we have a strong foundation to build upon.
Lastly, now that we have line of sight of the regulatory past. This year, we have plans to expand our commercial organization for launch readiness.
This includes adding to our field force to reach more Nephrologist building upon our best practices for Fujio engagement with health care providers and ready in the distribution and patient support services infrastructure.
Peter Heerma: Building upon our best practices for virtual engagement with healthcare providers and readying the distribution and patient support services infrastructure, all ahead of launch so we can hit the ground running is approved. With an anticipated addressable U.S. IgA nephropathy patient population of 30 to 50,000 people at launch, we recognize the significant potential for this market if Sparcentum is approved. We have started early and are investing and building appropriately to position ourselves for success. Most importantly, we are doing this from a differentiated position of strengths.
All ahead of loss. So we can hit the ground running is approved.
Was it anticipated addressable U S. Iga nephropathy patient population of 30% to 50000 people at launch we recognize the significant potential for this market if sports Anthony is approved.
We have started early.
Investing and building appropriately to position ourselves for success.
Most importantly, we are not doing just from what we are doing just from a differentiated position of strengths. We are not starting from scratch, but instead building. Upon the team that has leadership experience in rare nephrology and has demonstrated for more than six years that against successfully identify tweet and support patients lives.
Peter Heerma: We are not starting from scratch, but instead building upon a team that has leadership experience in rare nephrology and has demonstrated for more than six years that it can successfully identify, treat, and support patients living with rare diseases. I will now turn the call over to Laura for the financial update.
With rare diseases.
Laura Klag: Thank you, Peter. For the fourth quarter of 2021. We reported net product sales of $54.6 million from our commercial portfolio compared to $51 million for the same period in 2020. For the full year 2021, we reported $210.8 million in net product sales. Total revenue for the full year 2021 was $227.5 million, consisting of $210.8 million in net product sales and $16.7 million in licensing and collaboration revenue from our European partnership with V4Pharma. We reported a gap net loss of $51.6 million for the fourth quarter of 2021. For the full year 2021, gap net loss was $180.1 million.
Let me now turn the call over to Laura for the financial update.
Good morning.
Thank you Peter.
For the fourth quarter of 2021, we.
We reported net product sales of $54 6 million from our commercial portfolio compared to 51 million for the same period in 2020.
For the full year 2021, we reported $210 8 million and net product sales.
Total revenue for the full year 2021 for $227 5 million, consisting of $210 8 million and net product sales and $16 7 million in licensing and collaboration revenue from our European partnership with <unk> pharma.
We reported a GAAP net loss of $51 6 million for the fourth quarter of 2021.
For the full year 2021, GAAP net loss was $180 1 million.
After adjusting for noncash expenses and income tax.
Reported a non-GAAP net loss of $37 6 million for the fourth quarter and $100 million for the full year 2021.
Laura Klag: After adjusting for non-cash expenses and income tax, we reported a non-GAAP net loss of $37.6 million for the fourth quarter and $100 million for the full year 2021. On a gap basis, R&D expenses were $62.2 million for the fourth quarter and $210.3 million for the full year 2021. The increase compared to 2020 is largely attributable to increased patient enrollment in the ongoing studies of Sparsentine, as well as advancement of the PEG-to-Batinase program in HCU.
On a GAAP basis, R&D expenses were $62 2 million for the fourth quarter and $210 3 million for the full year 2021.
The increase compared to 2020 is largely attributable to increased patient enrollment in the ongoing studies are statin as well as advancement is it takes about <unk> program in HCM.
Laura Klag: On an adjusted basis, R&D expenses were $57.7 million for the fourth quarter and $196.2 million for the full year 2021. Relevant non-cash expenses for the fourth quarter included $4.4 million of stock-based compensation and amortization. On a gap basis, selling, general, and administrative expenses for the fourth quarter were $42.1 million, and $149.9 million for the full year 2021.
On an adjusted basis R&D expenses were $57 7 million for the fourth quarter.
$196 2 million for the full year 2021.
Relevant noncash expenses for the fourth quarter included $4 4 million of stock based compensation and amortization.
On a GAAP basis, selling general and administrative expenses for the fourth quarter were $42 1 million and $149 9 million for the full year 2021.
Laura Klag: The increase compared to 2020 is largely attributable to increased headcount and professional fees as a result of the company's operational growth as it prepares for potential commercial launch. On an adjusted basis, SP&A expenses for the fourth quarter were $30.9 million and $106.6 million for the full year 2021. Significant non-cash adjustments for the quarter consisted of $11.2 million in stock-based compensation and depreciation and amortization.
The increase compared to 2020 is largely attributable to increased headcount and professional fees as a result of the company's operational growth as we prepare for potential commercial launches.
On an adjusted basis SG&A expenses for the fourth quarter were $30 9 million and $106 6 million for the full year 2021.
Significant noncash adjustments for the quarter consisted of $11 2 million in stock based compensation and depreciation and amortization.
As we look ahead to 2022, we are not providing specific net product sales guidance as this is a transitional year.
Laura Klag: As we look ahead to 2022, we are not providing specific net product sales guidance as this is a transitional year with the expected impact on Sciola sales from generic competition and the potential launch of Sparcentin in the fourth quarter. As has been typical for us in years past, we do anticipate higher growth to net discounts in the first quarter, driven by insurance coverage changes in the beginning of the new year. From an OpEx perspective, we anticipate that our R&D expenses will continue to run at a rate slightly higher than in the fourth quarter.
Brexit impact on <unk> sales from generic competition and the potential launch of <unk> in the fourth quarter.
As has been typical for us in past in years past, we do anticipate higher gross to net discounts in the first quarter driven by insurance coverage changes in the beginning of the new year.
From an Opex perspective, we anticipate that our R&D expenses will continue to run at a rate slightly higher than in the fourth quarter.
Laura Klag: This is representative of the ongoing duplex and protect studies that will continue into 2023, as well as the ongoing composed study of PEG-2-Batinase and foundational work, including scaling CMC to prepare for a pivotal program. We also expect meaningful increases in FDNA, particularly in the second half of this year, as we look to continue the commercial build-out, including additions to our field team for the potential Sparsanton launch in Idaena Province.
This is representative of the ongoing duplex and protect studies that will continue into 2023 as well as the ongoing composed savviest paid to bat and foundational work, including scaling CMC to prepare for a pivotal program.
We also expect meaningful increases in SG&A, particularly in the second half of this year as we look to continue the commercial buildout, including additions to our field team.
Potential <unk> launch in Iga nephropathy.
Importantly, we continue to be in a strong financial position to execute in 2022 and beyond.
We ended the year with $552 9 million in cash and cash equivalents.
Laura Klag: This balance includes $30.8 million in net proceeds from our at-the-market facility during the fourth quarter. Taking into account the potential impact of a more genericized Biola market but not yet factoring in the full pivotal program for PEG to Batinase, we anticipate this cash balance will support our planned operations through 2023. I now hand the call back over to Eric for his closing comments.
This balance includes 38 $30 8 million in net proceeds from our aftermarket facility during the fourth quarter.
Taking into account the potential impact of a more generic size by all the market, but not yet factoring in the full pivotal program for <unk>. We anticipate this cash balance will support our planned operations through 2023.
Let me now hand, the call to Eric for his closing comments Eric.
Thank you Laura.
Eric Dube: Thank you, Laura. Our execution in 2021 has enabled us to enter this new year with great momentum and an incredibly bright outlook. Our priorities for 2022 are clear.
Our execution in 2021 has enabled us to enter this new year with great momentum and incredibly bright outlook our priorities for 2022 are clear.
Eric Dube: We will remain focused on positioning Sparsentin to become a new treatment standard for IJ nephropathy and FSGS if approved. This includes achieving on-time and high-quality regulatory submissions, the first of which could enable an approval of Sparsentin for IJ nephropathy by the end of this year. We will also focus on continuing to advance our PEG-to-Batinase program following the exciting proof-of-concept data in HCU reported in December.
We'll remain focused on positioning <unk> to become a new treatment standard for Iga nephropathy and <unk>. If approved this includes achieving on time and high quality regulatory submissions.
First of which could enable an approval of <unk> for Iga nephropathy by the end of this year.
We will also focus on continuing to advance our pegged about in these program. Following the exciting proof of concept data in HCC you reported in December .
Eric Dube: And in parallel to focusing on the advancement of our pipeline, we will further prepare our organization for the potential upcoming launches of Sparcentin by building upon our proven commercialization capabilities in rare nephrology. Let me now turn the call over to Chris for Q&A. Chris?
And in parallel to focusing on the advancement of our pipeline. We will further prepare our organization for the potential upcoming launches thus far center by building upon our proven commercialization capabilities in rare Nephrology, Let me now turn the call over to Chris for Q&A Kris.
Alright. Thank you Eric Brandon can we please go ahead and open up the lines for Q&A.
Christopher Cline: Great, thank you, Eric. Wayna, can we please go ahead and open up the lines for Q&A? Absolutely. As a reminder to ask a question, please press the star then the number one on your telephone. To withdraw a question, press the bank.
Absolutely as a reminder to ask a question. Please press the Star then the number one on your telephone.
The dry question <unk>.
Operator: Your first question is from Greg Harrison of Bank of America. Your line is open. Hey, good afternoon, and thanks for taking our questions. On FSGS, what would you consider to be supportive EGFR data, in your opinion? And if that were not considered to be sufficient for filing, What would be required for a filing?
Your first question is from Greg Harrison of Bank of America. Your line is open.
Hey, good afternoon, and thanks for taking our questions.
On SSG.
What would you consider to be supportive Egfr data.
Your opinion and if that were not considered to be sufficient for filing.
What would be required to.
For a filing would you have to complete the entire study or.
Gregory Harrison: Would you have to complete the entire study or could there be another interim analysis performed? Greg, thanks so much for the question. Bill, why don't you speak to the regulatory expectations with the FSGS data? And Jula, perhaps you can speak a bit to what might be supportive from a nephrologist perspective. Bill?
Could there be another interim analysis performed.
Great. Thanks, so much for the question Bill.
Bill why don't you speak to the regulatory expectations with the <unk> data.
Perhaps you can speak a bit to what might be supported from a nephrologist perspective.
Bill.
William Rote: Certainly, I'll start with the construct of the trial. The primary endpoint for approval under subpart H accelerated approval is proteinuria. And we've met that milestone with a very robust, Superiority of Sparsanthin over Herbicidin. But in that accelerated approval.
Certainly I'll start with the constructive the trial the primary endpoint for approval under Subpart H accelerated approval.
As proteinuria and we've met that milestone with the very robust superiority of <unk> over irbesartan.
But in that accelerated approval.
Rubric for the FDA criteria is that the totality of the data are.
Generally supportive or reasonably likely to support or to predict.
Success at the two year endpoint.
So in that case the agency is going to be looking to see are the trends. There that are consistent with the hypothesis that this level of proteinuria reduction should yield.
William Rote: I am, that this level of protein urea reduction should yield a preservation of renal function and in this case that would be shown by a separation in the EGFR slopes at two years. I'll hand over to Jula for the nephrologist. Certainly, thanks. Well, recall in duet that there was an early acute EGFR decline and then a flattening with sparsentan, and this is consistent with the nephroprotective agents such as SGLT2 inhibitors and RAS inhibitors. And the key is to understand the nature of the curve, as a reduction in proteinuria should flatten the EGFR curve and then provide long-term nephroprotection.
Preservation of renal function and in this case that will be shown by the separation in the egfr slopes at two years I'll.
I'll hand over to July for the Nephrologist viewpoint.
Certainly thanks will recall and get wet, but there was an early acute egfr decline and then a flattening with bar Fan-tan and this is consistent with the network protective.
<unk> agents, such as <unk>, two inhibitors and RAF inhibitors and the key is to understand the nature of the curve as the reduction in proteinuria should flatten the Egfr curve and then provide long term NAV for protection. So for duplex there'll be a matter of having enough egfr data that is mature enough to predict that.
Jula Inrig: So for duplex, it will be a matter of having enough EGFR data that is mature enough to predict the two-year EGFR slope. Thank you, Bill and Jula. And Greg, just to complete out the last part of your question around, you know, if FDA does not deem the additional EGFR data sufficient for subpart H submission, what next? Well, I think we first believe that the profile sparsensin will, you know, if behaving like we expect, it should support the, you know, longer term two year difference that we expect.
<unk> Egfr slope endpoint.
Thank you Bill and Joe and Greg just to complete up the last part of your question around.
FDA does start to the additional egfr data sufficient for subpart H submission what next.
I think we first believed that the profile of <unk> and will.
If behaving like we expect it should.
Support.
Longer term to your difference that we expect and we are.
Jula Inrig: And we are committed to completing this trial out to the two years. So, if for some reason FDA says, you know, we wouldn't support a subpart H, we would evaluate, but our plan certainly would be to complete the trial and then submit for full approval at that point. And just a reminder, we would expect the last patient last visit for the two year endpoint to occur in the first half of next year. Great, that's helpful. Thanks again and congrats on the progress. It's exciting to see you guys getting close to the finish line.
Added to completing this trial out to two years. So if for some reason FDA says.
We wouldn't support a subpart H, we would evaluate but our plan certainly would be to complete the trial and then submit for full approval at that point and just a reminder, we would expect the last patient last visit for the two year endpoint to occur in the first half of next year.
Great. That's helpful. Thanks, again, and congrats on the progress it's exciting to see you guys getting close to the finish line.
Eric Dube: Indeed. Thank you, Greg. Your next question is from Carter Gould of Barclays, your line is open. Yeah, hey, this is Justin. I'm for Carter.
Thank you Greg.
Your next question is from Carter Gould of Barclays. Your line is open.
Yeah, Hi, this is Justin on for Carter Congrats on all the progress this year.
Carter Gould: Congrats on all the progress this year. Another one on the interim readout for duplex, sort of how long after discussing those data with FDA, do you expect to be ready to file for approval? And then, you know, sort of related to that, do you expect to file the combo MAA in Europe, you know, around the same time as the NDA? Or is one of those going to proceed? Yeah, so great questions, Justin. Thank you for them.
Another one on the interim readout for duplex sort of how long after discussing those data with FDA do you expect to be ready to file for approval and then sort of related to that do you expect to file the combo MAA in Europe .
Around the same time as the NDA or is one of those going to pursue together.
Yes, so great question Justin Thank you for for that Bill would you like to talk about the timing just as a reminder, overall, we would expect those filings assuming.
Eric Dube: Bill, would you like to talk about the timing? Just as a reminder, overall, we would expect those filings, assuming, you know, the regulators are supportive of the additional EGFR data, we'd look to do that in the middle of this year. Bill perhaps can provide a little bit more color on the timing and sequence.
The regulators are supportive of the additional Egfr data, we'd look to do that in the middle of this year built perhaps can provide a little bit more color on the timing and sequence.
Yes, I think the preparation is well underway just in working on those filings.
William Rote: Yeah, I think the the preparation is well underway, just in working on those filings. Now, so that once we do have that supplemental look at the EGFR data, we can tuck those additional data in and submit very quickly. So we've guided mid-year for both of those filings. They're going to be very close to one another because they're both essentially waiting for that additional data to be available, and then we'll have the conversation with the agency, and in the scenario where they are, as we expect, supportive, that will be the last elements to drop in so that we're ready to file quickly. Awesome. Thanks so much.
So once we do have that supplemental look at the Egfr data, we can tuck those additional data in and submit very quickly. So we've guided mid year for both of those filings.
We're going to be very close to one another because they are both essentially waiting for that additional data.
To be available and then we will have the conversation with the agency and.
In the scenario, where they are as we expect supportive.
That will be the last elements to drop in so that we're ready to file quickly.
Awesome. Thanks, so much.
Yes.
Thanks, Joe.
Unknown Attendee: Thanks, Joseph. Your next question is from Joseph Schwartz of SVB Link. Your line is open.
Your next question is from Joseph Schwartz with SBB Leerink. Your line is open.
Alright, thanks very much.
Joseph Schwartz: Hi, thanks very much. To what extent will you be scrutinizing the merit of the protein area and EGFR effects in the next look at the duplex data in order to determine whether it makes sense to show to the FDA? In other words, is there a scenario where you would not submit the data to the FDA if it were not supportive, however remote? If so, how much would the data have to worsen beyond what you've already seen?
To what extent will you be scrutinizing, the merit of the proteinuria and Egfr effects in the next look at the <unk> complex data in order to determine whether it makes sense to show to the FDA in other words is there a scenario where you would not submit the data to the FDA.
Not supportive.
However, remote.
If so how much would the data have to worsen beyond what you've already seen.
Eric Dube: in order to lead you not to submit the data to the FDA. Joe, thank you for the question. I think first I'll just reinforce that our view is that Sparsantan overall has performed very consistently throughout our clinical program, and so, you know, we do believe that, you know, Sparsantan does behave the way that it has and the way that we expect that there will be, you know, a continued improvement over time.
In order to lead you not to submit the data to the FDA.
Joe. Thank you for the question I think first of all.
I'll just reinforce that our view is that sports center and overall has performed very consistently throughout our clinical program and so we do believe that.
<unk> does behave the way that it has and that we expect that there will be.
Our continued improvement over time, but I'll ask Julie to comment on what type of assessment would you be looking with these whats that limited kind of evaluation that will be done.
Eric Dube: But I'll ask Jula to comment on, you know, what type of assessment would you be looking with these, and, you know, what's that limited kind of evaluation that will be done? Certainly. So the only evaluation is EGFR. We've already seen the magnitude of the proteinary reduction from the top line results.
Certainly so the only evaluation is egfr, we've already seen the magnitude of the proteinuria reduction from the top line results. So we are just looking at Egfr and the additional maturity of the data.
Jula Inrig: So we are just looking at EGFR and the additional maturity of the data to be predictive of the long-term EGFR benefit. And we believe that the proteinary reduction is meaningful. And then really, as I said, it's just looking at the EGFR data at that point. Okay, great, that's very helpful, thank you.
To be predictive of the long term egfr benefit and we believe that the proteinuria reduction is meaningful and.
And then really as I said, it's just looking at the Egfr data at that point in time.
Okay, Great. That's very helpful. Thank you and then maybe another question.
Unknown Attendee: And then maybe another question, but this one relating to IgA nephropathy. Given there was a recent approval and pricing and launch of another therapy, I was wondering, I'm thinking of Tarpaio, and you mentioned you were doing some considerable work in terms of pharmacoeconomic. I was wondering, you know, how does the pricing for that agent compare with some of the work that you've been doing in preparation for determining a price for SPARS and TAN and IGA and EFRA?
But this one relating to <unk>.
<unk> nephropathy, given there was a recent approval in.
Pricing and launch of another therapy.
I was wondering.
I'm thinking of TARP.
Is.
And you mentioned you were doing some.
Considerable work in terms of hormonal economics.
I was wondering how does the pricing for that.
<unk>.
Compare with some of the.
Work that you've been doing in preparation for.
Determining a price for as far as <unk> and Iga nephropathy.
Yes. So thank you for the question I think first we were quite pleased now to see a precedent from a regulatory approval and the use of proteinuria with the approval of Budesonide and so we think it further bolsters our confidence I'll ask Peter to talk a little bit about how we think about pricing.
Joseph Schwartz: Yeah, Joe, thank you for the question. I think first, we were quite pleased now to see a precedent from a regulatory approval and the use of proteinuria with the approval of budesonide. And so, you know, we think it further bolsters our confidence. I'll ask Peter to talk a little bit about how we think about pricing and, as you say, the pharmacoeconomic evidence to support pricing and access for sparsentin. Peter?
And as you said the Pharmacopeia economic evidence.
Evidence to support pricing and access for <unk>.
Peter.
Peter Heerma: Yeah, certainly, Eric. And thank you for the question. I think it's good to start with like, what is the unmet need? And we know the unmet need, in particular, in IJ nephropathy, but also in FSGS, it's among the most difficult patients to treat for nephrology. And in particular, for the current standard of care, it's because patients are not being treated well to the targets that physicians want with age inhibitors and ARBs. And that's where we see the sweet spot for sparse entom.
Yeah, certainly Eric and thanks for the question.
It's good to start with like what is the unmet need and we know the unmet need and particularly in Iga nephropathy, but also yes.
Yes.
Among the most difficult patients.
$3 four nephrologist and in particular for the current standard of care because.
But being treated well to the targets that's positioned well with ace inhibitors from <unk> and Thats why we see the sweet spot for sparse anthem.
Peter Heerma: That's what we're hearing from patients, as well as from nephrologists, that they're very excited about the profile, because they see this as a new standard of care, potentially replacing Asian ARBs, without having the need to go to the steroid path. And so our work, our planning, our positioning will be to take that foundational position, and our pricing will be consequential. With regards to the pricing you referenced, I think there is now multiple products in the rare nephrology space in the last year in particular, including Bodefinide that you were referencing.
Hearing from patients as well as from Nephrologist that they are very excited about the profile because they see this as a new standard of care potentially replacing agent arms without having the need to go to just deal with that.
So our work our blending our positioning will be to take that the foundational position and our pricing will be.
We'll be consequently, with regards to the pricing you referenced I think just now multiple products in the round nephrology space in the last year in particular, including but Thats what might that you were referencing and I think thats allows us to sort of level of flexibility, but again like we see <unk> as a new potential.
As a new standard of care and we will be pricing accordingly.
Thanks for taking my questions.
Thank you Joe.
The next question is from Maury Raycroft of Jefferies. Your line is open.
Peter Heerma: And I think that allows us a certain level of flexibility. But again, like we see SparCentre as a new potential of care and as a new standard of care, and we will be pricing accordingly. Thanks for taking my question. Thank you, sir [inaudible] Your next question is from Maurice Raycroft of Jeffries. Your line is open. Maurice Raycroft, your line is open. Wayne, and maybe let's come back to Maury.
Okay.
Maury Raycroft your line is open.
Yes.
And maybe let's come back to Maury.
Your next question is from Michelle Gilson of Canaccord Genuity. Your line is open.
Maurice Raycroft: Your next question is from Michelle Gilson of Canaccord Genuity, your line is open. Hi, can you guys hear me? Yes, we can. Hi, Michelle. Hi, thank you for taking my question. I guess a couple of pegs to that, Nace. You indicated when you presented the data in December, that you were planning to meet with the ACA in the first quarter of this year to get aligned on, you know, potential pivotal trials.
Hi can you guys hear me.
Yes, we can hi, Michelle.
Hi, Thanks for taking my question.
I guess, a couple of them talked about knees.
You indicated when you.
Presenting the data in December that you are planning to meet with FDA in the first quarter of this year.
To get aligned on.
Sure.
Maurice Raycroft: I was just curious if, you know, if you guys have had that meeting. And then, you know, when it comes to total home assistance as a surrogate endpoint, or as a biomarker, You know, can you maybe discuss, you know, how established the link is with homocysteine and clinical outcomes in homocysteineuria? And just, you know, maybe, you know, if the FDA does ask you to, to run a trial with a clinical outcome endpoint, you know, what kind of options do you have? Michelle, thank you so much for the questions. Bill, would you like to take those? Sure, I'd be happy to. And clearly the dog is a big fan of Peg Tibet. Oh yeah, they're very big fans.
Yes.
I was just curious.
If you guys have had that meeting and then when it comes to total homeless is seen as a surrogate endpoint or is.
As a biomarker.
Yes.
Can you maybe discuss how established the linkage with 15 in clinical outcomes in Homewood in.
In homeowners the scenario.
Hi.
And just maybe.
If the FDA does ask you too.
To running trial with a clinical outcome endpoint, what kind of options do you have.
Yes.
Michelle. Thank you so much for the question Bill would you like to take those.
Sure I'd be happy to.
Clearly the dog is a big fan of peg to that news.
Sure Barry.
Chad.
William Rote: Yes. Remember, with respect to the FDA and the discussions around endpoints for phase three, remember that we've made the comment in the past that this is an iterative process. There are multiple elements to that agreement around the assay, establishing the biomarker according to guidance, and phase three clinical trial design. So it's more than just a one-step process.
Yes.
Remember with respect to the FDA in the discussions around.
Endpoints for phase III remember that we've made the comments in the past that this is an iterative process, there's multiple elements to that agreement.
Around the assay.
Establishing the biomarker according to guidance phase III clinical trial design. So it's more than just a one step process, we've begun that process with the agency.
William Rote: We've begun that process with the agency. We're now at a position where we can comment on it beyond the fact that we're pleased with the directions that it's going, and we'll update as we get to a point of completion and we have more certainty around what that path looks like. The second part of your question was really, I believe, around the links between reductions in homocystinuria and that linkage to clinical impact.
We're not in a position where we can comment on it beyond the fact that we're pleased with the direction that its going and we'll update as we get to a point of completion and we have.
More certainty around what that path looks like.
The second part of your question was really I believe around the links between reductions in homeless cystinuria.
That linkage to clinical impacts if you look at the guidance.
William Rote: If you look at the guidance that is out there that suggests, that guides physicians to get total homocysteine below 100. That guidance was set based on looking at, patients, their levels of homocysteine and their incidence of clinical events, whether it's issues with eye, bone, thrombotic events, or cognitive issues. And the overall conclusion was that when they get below 120 micromolar, that those clinical events, become very rare. They set the guidance at 100 micromolar because it gave them some breathing space and was easy to remember.
That is is out there.
Suggest that.
On the guidance positions to preach to get total homes <unk> below 100 that guidance was set based on looking at.
Patients their levels of homocysteine.
And their incidence of clinical events weather issues with <unk>.
Boon <unk>.
Embolic events or cognitive issues and the overall.
<unk> was that when they get below 120 micro molar that those clinical events.
Become very rare.
Set the guidance at 100 micro molar because it gave them some breathing space.
And with easy to remember.
William Rote: So the retrospective data is there with the linkage between the clinical endpoints and the overall levels of homocysteine. We also have is the natural history study data coming from, The ongoing study that we have that fits and confirms that events are indeed linked to, Total Homelessness Team. So we'll be packaging that together in making our arguments. I think the final piece of your question... It looks like, can you hear me?
So the retrospective data is there with the linkage between the clinical endpoints and the.
Overall levels of homocysteine.
What we.
We also have as the natural history study data coming from.
The ongoing study that we have that.
And confirms.
Events R&D linked to <unk>.
Total homeless his team so we will be packaging that together.
And making your arguments I think the final piece of your question.
It looks like can you hear me it looks like we might have lost.
William Rote: It looks like we might have lost Bill's connection. So, Michelle, the last part of your question... Oh, and he's back. No, go ahead. We can hear you to realize that we, We will be making clinical measurements. They just won't be primary endpoints.
<unk> connection so.
So Michelle the last part of your answer.
Oh.
These back they'll go ahead, we can hear you now to realize that.
We will be making clinical measurements. They just won't be primary endpoints, we will look at ocular.
Bill I think we're having some some.
Eric Dube: We will look at ocular... Bill, I think we're having some some, Audio Difficulties. Maybe if I can frame Michelle, the last part of your question, which is, do we believe that there would be a need for clinical outcomes in phase three program. And I think, you know, certainly as Bill has mentioned, we'll be looking at that at secondary measures, both for the ongoing phase one to compose study, as well as likely in any phase three, although we haven't yet reached agreement on what that trial design could look like. You know, homocysteine urea is certainly one of those diseases that is heterogeneous both in the presentation of the disease as well as the the kind of time to onset of some of those.
Audio difficulties, maybe if I could.
Frame Michelle the last part of your question, which is do we believe that there would be a need for clinical outcomes in our phase III program and I think certainly as Bill had mentioned, we'll be looking at that at secondary measures. Both for the ongoing phase one two composed study as well as likely in any phase III although.
We haven't yet reached agreement on what that.
Trial design could look like.
Home Assistant area is certainly one of those diseases that is heterogeneous both in the presentation of the disease as well as the.
Eric Dube: And so it's that heterogeneity that would make it very difficult to select a particular clinical outcome in a development program, which is why we're so focused on ensuring that total homocysteine or biomarker can be used for further development given, again, that this is an ultra-rare condition that would be a challenge to have a phase three with a clinical endpoint. So more to come on that, and I think what's important is you know, there is more engagement and work that will be done this year to ensure that we have that alignment with regulators and can move forward with the next phase of development, and Bill. I'm not sure if we have you back. Okay. Michelle, hopefully that answers your question. And I think hopefully we'll have a resident expert back here. All right, sounds good. I can have Bear come back on.
The kind of time to onset of some of those and so the heterogeneity that would make it very difficult to select a particular clinical outcome in a development program, which is why we're so focused on ensuring that total from assisting our biomarker can be used for further development.
Again this is a it's an ultra rare condition.
What would be a challenge to have a phase III with <unk>.
Our clinical endpoints, so more to come on that and I think what's important is.
There is more and more.
<unk> and work that will be done this year to ensure that we have that alignment with regulators and can move forward with the next phase of development.
And Bill Im not sure if we have you back.
Okay.
Michel hopefully that answers your question and I think hopefully we will have our resident expert back here soon.
Alright sounds good I can have bear come back on.
Okay.
Thanks for taking my question.
Thank you Michelle.
Your next question is from <unk> <unk> of Evercore ISI. Your line is open.
Michelle Gilson: Thank you for taking my question. Your next question is from Liisa Bayko of Evercore ISI, your line is open. Hi, thanks for taking the question. I just wanted to see if you could give us a little color. Maybe you have talked about this before, but we just wanted to confirm on the data that you're going to deliver to FDA on FSGS. Is that like one year?
Hi, Thanks for taking my question I just wanted to see if you could give us a little color. Maybe you have talked about this before but we just wanted to confirm on.
The data that youre going to deliver to FDA on FX, yes is that like one year.
<unk>.
Liisa Bayko: Estimated GFR, is that is that what it is that all the patients have been through one year? Could you just kind of give us some sense of that thing? Sure. Jula, would you like to take that?
Estimated GFR is that is that what it is that all the patients have been through one year could you just kind of give us some sense of that.
Yes.
Jula Inrig: And Liisa, thank you very much for the question. So the additional data, 50% of the patients, will be at two years and a hundred percent of the patients will be at one year for the EGFR data. And so it'll be a much more mature data set for with regards to EGFR and that's the data that we're going to be providing. Okay, great. Thank you. Thank you, Lisa. Your next question is from Maurice Raycroft of Jeffries. Your line is open.
Sure Julian would you like to take that Lisa. Thank you very much for the question.
So the additional data 50% of the patients.
Yes.
We'll be at two years and 100% of the patients will be get one here for the Egfr data and so it'll be a much more mature dataset with regards to Egfr and thats the data that we're going to be providing.
Okay, great. Thank you.
Thank you Lisa.
Okay.
Your next question is from Maury Raycroft of Jefferies. Your line is open.
Hi, Thanks for taking my question and congrats on the progress.
Maurice Raycroft: Hi, thanks for taking my question and congrats on the progress. I was going to ask a question just based on the Tarpaio launch. Do you have an updated view on how you see the treatment paradigm shaping up? And if you have any feedback from payers on replacing traditional RAS inhibitors, or will you have to step through traditional RAS inhibitors?
I was going to ask a question just based on the <unk> launch.
Do you have an updated view on how you see the treatment paradigm shaping up and if you have any feedback from payers on replacing traditional Ras inhibitors or will you have to step through traditional traditional Ras inhibitors. I guess, how are you guys thinking about that.
Maurice Raycroft: I guess, how are you guys thinking about that? More, thanks so much for the questions, Jula. Maybe I'll start with you.
Jula Inrig: You can talk about how you might see the landscape evolving. And then Peter, if you can add anything further as we think about commercialization and any feedback from payers. Sure, well there remains a huge unmet need for patients with protoneric kidney diseases and we basically treat patients who have protonery above 0.75 grams per day or 0.5 with RAS inhibitors and that's our foundation and we envision Sparcentan to be the initial therapy or foundational therapy if approved.
Thanks, so much for the questions maybe I'll start with you you can talk about how you.
Might see the landscape evolving and then Peter if you can add anything further as we think about commercialization and any feedback from payers.
Sure well there remains a huge unmet need for patients with kidney diseases and.
We basically treat patients who have proteinuria above 75 grams per day or five with RAF inhibitors, and Thats, Our foundation and we envision <unk> to be the initial therapy or foundational therapy if approved.
Jula Inrig: The utilization of steroid therapy historically and likely going forward is outlined in the KDGO guidelines, which we only use it in a subset of patients who are really at high risk of progression in those who have either a rapid decline in EGFR, very high-protonerian.
Utilization of steroid therapy, historically and likely going forward is outlined in the <unk> guidelines, which we only use it in a subset of patients who are really at high risk of.
Progression in those who have either a rapid decline in Egfr very high preliminary and I don't really envision that changing based on our guidelines and based on what we know and it's really a risk benefit ratio that we do in patients and when we decide to use that therapy or pull that in.
Peter Heerma: I don't really envision that changing based on our guidelines and based on what we know, and it's really a risk-benefit ratio that we do in patients and when we decide to use that therapy or pull that in. Yeah, and building on that, Maury, so the introduction of bedafinide is not changing the way we think about the introduction of sparse symptom, the potential it has to become a new standard of care. What we are hearing from our physicians as well as from patient societies is that they're feeling very comfortable on the position of sparse symptom to replace current standards of care, ACE inhibitors and ARBs, and so positioning it before the use of steroids and allowing that additional option later on in the pathway. So to your question, it doesn't change the way we are thinking about it.
Yes.
Yeah and building on that Marty So the introduction of the desk night is not changing the way, we think about the introduction of <unk> and the potential it has to become a new standard of care.
But we are hearing from our physicians as well as from patients' societies that they are feeling very comfortable on the <unk>.
Additional sparse interim to replace current standards of care.
Inhibitors, arby's and so positioning it before do you.
Steroids, and allowing that additional option later on in the past way. So to your question. It doesn't change the way we are thinking about it.
Peter Heerma: On your second part of the question with regards to payers, I think we are pleased with the interest that payers have. We're building the value proposition. We're building the burden of disease and the natural history of the disease to have a meaningful conversation with the payers. But we are pleased where we are. And again, the introduction of bedazolamide is not changing the way we position sparseness.
Your second part of the question with regards to payers I think we are pleased with the interest of payers have we are building the value proposition. We are building the burden of disease and the natural history of the disease to have a meaningful conversation with the players, but we are pleased where we are.
And again, the introduction of all but that's a nice about changing the way we position spar symptom.
Yeah, and I think specifically thank you Peter for that maybe just one other thing that I'll add more to your question around do we think that we would need to step through an ace or arb I think given.
Eric Dube: Yeah, and I think, you know, specifically, thank you, Peter, for that. Maybe just one other thing that I'll add, Maury, to your question around, do we think that we need to step through an ACE or an ARV? I think given in hygiene nephropathy that the patients that are currently being treated, nearly all of them are on an ACE or an ARV, it's highly likely that, you know, those patients would, if still having elevated proteinuria, would likely be, you know, stepped up to or switched to sparsensin.
The property has got.
The patients that are currently being treated nearly all of them are on an ace or an arb, it's highly likely.
That those patients would still having elevated area would likely be stepped up to or switch to spar sentence. So whether it's July highlighted that in the future patients may start on <unk> or on an ace or an arb and then our stepped up we actually don't see that as an issue or barrier for us.
Laura Chico: So, you know, whether it's, as Jula highlighted, that in the future, patients may start on sparsensin or on an ACE or an ARV and then be stepped up, we actually don't see that as an issue or a barrier for us, particularly given that so many of these patients still have elevated proteinuria and are at great risk of progression. So, you know, I think it underscores the role that we believe sparsensin will play as a foundational treatment within this disease. Okay, now I think we can go ahead and move to the next question, please. Your next question is from Laura Chico of Wedbush.
Particularly given that so many of these patients still have elevated area and are at great risk of progression. So I think it underscores the role that we believe <unk> will play is becoming a foundational treatment within this disease.
Yes.
Okay. Now I think we can go ahead and move to the next question. Please.
Your next question is from Laura Chico of Wedbush. Your line is open.
Hey, good afternoon, guys. Thanks for taking my question.
Laura Chico: Hey, good afternoon, guys. Thanks for taking my question. I apologize, because this is going to be a pretty naive one. But I wanted to ask on duplex.
I apologize because this is going to be pretty naive one, but I wanted to ask on duplex.
Im wondering if you could just kind of walk me through the communication strategy essentially what level of detail should investors be anticipating with respect to the.
Interim analysis here, that's coming up and I guess I'm asking is I'm not really clear I just want to make sure that we're all clear on in terms of what data should be anticipated I know you've been cautioned by the FDA on certain disclosures. So I'm just trying to understand what visibility we as investors will have with respect to the interim update thanks.
Laura Chico: I'm wondering if you could just kind of walk me through the communication strategy. And essentially, what level of detail should investors be anticipating with respect to the interim analysis here that's coming up? And I guess I'm asking because I'm not really clear.
Laura Thank you very much for the questions certainly not not even at the very important one is we can help provide as much clarity.
Laura Chico: I just want to make sure that we're all clear on terms of what data should be anticipated. I know you've been cautioned by the FDA on certain disclosures. So just trying to understand what visibility we, as investors, will have with respect to the interim update. Thanks. Laura, thank you very much for the question. Certainly not naive.
In the coming months I think what's important is that we are on track for the additional data on Egfr that we will provide two to FDA and EMA.
Eric Dube: It's a very important one, as we can help provide as much clarity in the coming months. I think what's important is that we are on track for the additional data on EGFR that we will provide to FDA and EMA. Those data to date have not been extracted, but we're on track to do that in the first half of this year.
Those data to date have not been extracted, but we're on track to do that in the first half of this year and.
Eric Dube: And at that point, we really will not be commenting on any of the process or any of the data. You will hear from us once we've had the meetings with regulators and that we have that direction from FDA on the potential submission timing and process. But nothing incremental before that happens.
At that point, we really.
We will not be commenting on any of the process or any of the data.
You will hear from US once we have had meetings with regulators and that we have that direction from FDA on the potential submission timing and process, but nothing incremental before that happens and so we're going to remain quiet on that front, but you can expect to hear from us once we do have.
Eric Dube: And so we're going to remain quiet on that front. But you can expect to hear from us once we do have that agreement. And then, of course, related to Sparcentin, expect to hear from us on the submission of our IGAN NDA this quarter, as well as when we would receive an acceptance from FDA of that NDA. So there will be quite a bit of communication. But as you point out, we are going to remain very vigilant in the integrity of that trial and not disclosing anything on EGFR.
That agreement and then of course related to <unk> and we expect to hear from us on the submission of our NDA this quarter as well as when we would receive an acceptance from FDA.
Of that NDA, so there will be quite a bit of communication, but as you point out we are going to remain very vigilant in the <unk>.
Tegra <unk> of that trial and not disclosing anything on Egfr.
Thanks, very much if that answers your question.
Laura Chico: Thanks very much. Hopefully, that answers your question. Yes, it does.
Yes. It does thanks, Sir okay. Thank you.
Your next question is from Tim Lugo with William Blair. Your line is open.
Eric Dube: Thanks, Eric. Okay. Thank you, Laura. Your next question is from Team Lito, Ophillion Blair. Your line is open. (inaudible) Hi team, this is John on behalf of Kim.
Hi, David This is John on for Tim. Thanks, So much for taking my question.
Unknown Attendee: Thanks so much for taking our questions. I was wondering if you could give us any more details on what additional data from the COMPOSE study, Planning to share at a medical meeting. What meeting might see that data at and how we should be looking at or is there anything that we should be looking for? John, thank you so much for the question. Jula, would you like to take this one?
I'm just wondering if you could give us any more details on what additional data from the composed study planning.
Planning to share at a medical meeting.
Meetings.
That data at and how we should be looking at or is there anything that we should be looking for in that additional data.
John Thank you so much for the question Julian would you like to take this one.
So we do expect to have additional detail from compose at a medical meeting this spring and it'll be detailed from the.
Jula Inrig: So we do expect to have additional details from COMPOSE at a medical meeting this spring, and they'll be details from the first five cohorts. And as we do with participation in any medical meeting, we'll provide the details at an appropriate time. Okay, thank you.
The first five cohorts.
And as we do with participation in any medical meeting we will provide the details at an appropriate time.
Okay.
Okay. Thank you.
Unknown Attendee: Thank you, John. No more questions; I would like to turn the call back to the presenters for the final remarks. All right, thank you very much.
Thank you John .
No more questions I would like to turn the call back to the percentage for the final remarks.
Eric Dube: And thank you all for joining us soon. This concludes our update for today. As you can tell, we have many exciting milestones ahead. We look forward to keeping you updated throughout the year. Have a great rest of your evening. This concludes today's conference call. Thank you for participating. You may now disconnect. [music] , , , , , , , , , , , , , , , , , , , , , , , , , , , [music] [inaudible] Music Music Music Music Music Music Music Music Music Music Music Music Music Music Music, [music]
Great. Thank you Dana and thank you all for joining us.
This concludes our update for today and as you can tell we have many exciting milestones ahead, and we look forward to keeping you updated throughout the year and have a great rest of your evening.
This concludes today's conference call. Thank you for participating you may now disconnect.
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