Q2 2021 Travere Therapeutics Inc Earnings Call

Q2 for noon, ladies and gentlemen, and welcome to that severe therapeutics second.

Operator: Good afternoon, ladies and gentlemen, and welcome to the Travere Therapeutics second quarter 2021 financial results and corporate update call. At this time, all participants are in a listen-only mode.

Second quarter, 2021 financial results and corporate update call.

Time, all participants are in a listen only mode. Later, we will conduct the question answer session and instructions will follow at that time, if anyone should require assistance during the conference. Please press star.

Operator: Later, we will conduct a question and answer session, and instructions will follow at that time. If anyone should require assistance during the conference, please press star then zero on your touchtone telephone. As a reminder, this conference call is being recorded. I would now like to turn the conference over to your host, Mr. Chris Cline. Please go ahead.

Then the zero on your Touchtone telephone as a reminder of this conference call is being recorded I would not like to turn the conference over to your host Mr. Chris Cline. Please go head.

Great. Thank you Jerome and good afternoon, everyone and welcome to trigger of Therapeutics second quarter 2021 financial results in the corporate.

Christopher Cline: And welcome to Travere Therapeutics' second quarter 2021 financial results and corporate update call. Thank you for joining us. Today's call will be led by our Chief Executive Officer, Dr. Eric Dube. Eric will be joined for prepared remarks by our Chief Medical Officer, Dr. Noah Rosenberg, Peter Heerma, our Chief Commercial Officer, and our Chief Financial Officer, Laura Clay. Dr. Bill Rote, Senior Vice President of Research and Development, will join us for the Q&A session.

The call.

Thank you for joining us today's call will be led by our Chief Executive Officer, Dr. Eric <unk>, Eric will be joined for the prepared remarks by our Chief Medical Officer, Dr. No Rosenberg, Peter harm on our Chief commercial officer, and our Chief Financial Officer, Laura like Dr. Bill Rote Senior Vice President of research and development will join us for the Q&A session before we begin.

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.

Corporate up the 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 for 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.

Slide by the statement. Please see the forward looking statement disclaimer on the company's press release issued earlier today as well as the risk factors section of our form 10-Q, and 10-K filed with the SEC.

Christopher Cline: We see the forward-looking statement disclaimer in the company's press release issued earlier today, as well as in the risk factors section in our Forms 10-Q and 10-K filed with the SEC. In addition, any forward-looking statements represent our views only as of the date such statements are made, July 29, 2021, and Travere specifically disclaims any obligation to update such statements to reflect future information, events, or circumstances. With that, I'll now turn the call over to Eric. Okay?

Additionally, any forward looking statements represent our views only as of the date such statements are made of July 29, 2021 interview of specifically disclaims any obligation to update such statements to reflect.

Future information events or circumstances with that I'll now turn the call over to Eric Eric.

Thank you, Chris and good afternoon.

Eric Dube: Thank you, Chris, and good afternoon. At the outset of the year, we highlighted the progression of our pipeline as a key priority in order to strengthen our position in the rare disease. At the heart of this priority is an organization-wide focus on positioning sparsentine to potentially become a new treatment standard for FSGS and IgG nephropathy. People living with FSGS and IG nephropathy have gone decades without adequate treatment options and limited innovation.

At the outset of the year, we highlighted the progression of our pipeline is a key priority in order to strengthen our position in the rare disease community at the heart of this priority as an organization wide focus on positioning.

Percentage to potentially become a new treatment standard for <unk> and Iga nephropathy, if approved people living with <unk> and Iga nephropathy have gone decades without adequate treatment options and limited innovation.

As a result, each of your thousands of patients with these disorders are advancing to kidney transplant or die.

Eric Dube: As a result, each year, thousands of patients with these disorders are advancing or dying. It is a collective understanding of this significant unmet need that drives our organization every day to help pave the way for new therapeutic options. Being at the forefront of these efforts can come with both achieving significant milestones, as well as challenges that must be overcome.

Dialysis.

It is the collective understanding of the significant unmet need that drives our organization every day to help pave the way for new therapeutic options for these patients being at the forefront of these efforts can come with both achieving significant milestones as well as challenges that must be overcome.

Eric Dube: This was evident in the first half of 2021, where we generated positive results from the interim proteinuria assessment of our pivotal duplex study of sparsentin and FSG, but subsequently heard from FDA that the interim data were not adequate to support an accelerated approval submission this year. However, we remain undeterred in our commitment to ultimately deliver Sparsantan as a potential new treatment standard for FSC. We remain confident in the interim data generated by the duplex study, the largest controlled interventional study in FSGS. These data build upon the strong proof of concept from the Phase II duet study and provide a consistent data package to further inform Sparsanton's profile.

This was evident in the first.

First half of 2021, where we generated positive results from the interim proteinuria assessment of our pivotal duplex study of <unk> and <unk>, but subsequently heard from FDA that the interim data were not adequate to support an accelerated approval submission this year.

Despite this we remain undeterred in our commitment to ultimate.

The liver sports center as a potential new treatment standard for <unk>, we remain confident.

Confidence in the interim data generated by the duplex study the largest controlled interventional study in <unk> to date.

These data build upon the strong proof of concept from the phase 2 duet study and provided consistent data package.

<unk> further informed spar sentence profile.

At our upcoming scheduled type a meeting this quarter, we look forward to continuing our constructive dialogue with FDA in an effort to pursue accelerated approval submission in the U S next year.

Eric Dube: At our upcoming scheduled Type A meeting this quarter, we look forward to continuing our constructive dialogue with FDA in an effort to pursue accelerated approval submissions in the U.S. Outside of the U.S., I am pleased to share that we have made progress on our ongoing regulatory discussions with the EMA. Based upon our latest interactions, we anticipate submitting an application for conditional marketing authorization of Sparcentin for the treatment of FSGS in Europe by the end of this year.

Outside of the U S. I am pleased to share that we have made progress on our.

Market to going regulatory discussions with the EMA.

Based upon our latest interactions we anticipate submitting an application for conditional marketing authorization of spar center for the treatment of <unk> in Europe by the end of this year no. It will go into a bit more detail shortly but we believe that if we continue to progress.

Eric Dube: Noah will go into a bit more detail shortly, but we believe that if we continue to progress according to plan, Sparcentin could be approved for FSGS in Europe during the first half of 2020. We also remain excited about the potential for sparsentine to become an important new treatment option for patients with IJ nephropathy. IJ nephropathy is the most common cause of primary glomerular nephritis and a leading cause of end-stage kidney disease.

On the plan <unk> could be approvable for <unk> in Europe during the first half of 2023.

We also remain excited about the potential for <unk> to become an important new treatment option for patients with Iga nephropathy Iga.

Iga nephropathy is the most common cause of primary <unk>.

The corollary nephritis, and a leading cause of end stage kidney disease.

If ultimately approved we believe there to be between 75000 and 120000 addressable patients at launch in the U S and Europe with room for greater patient identification through increased awareness and diagnosis overtime.

Eric Dube: If ultimately approved, we believe there will be between 75,000 and 120,000 addressable patients at launch in the U.S. and Europe, with room for greater patient identification through increased awareness and diagnosis over time. Our phase three PROTECT study evaluating sparsentin in patients with IgA nephropathy is progressing well. And we remain on track for top-line data from the 36-week interim proteinuria assessment next month. The interim assessment is designed to support potential accelerated approval submissions in the U.S. and Europe, which could result in the first approval for IgA nephropathy as early as November.

Over time.

Our phase III protect study evaluating <unk> in patients with Iga nephropathy is progressing well and we remain on track for top line data from the 36 week interim Proteinuria assessment next month.

The interim assessment is designed to support potential accelerated approval submissions in.

In the U S and Europe, which could result in the first approval for Iga nephropathy as early as the next year.

Eric Dube: Finally, in the pipeline, we are encouraged by progress made with the PEG-to-Batinase program, where we remain on track to see preliminary data from the Phase 1-2 study later this year. We will also be working to lay the foundation for our regulatory pathway in HCU by leveraging both data from the Phase I-II study and the ongoing natural history study. Lastly, I'd like to touch on our commercial portfolio.

Finally in the pipeline we are encouraged by progress made with the peg the Baton. These program, where we remain on track to see preliminary data from the phase <unk> study later this year, we will also be working to lay the foundation.

For a regulatory pathway and <unk> by leveraging both data from the phase 1.2 study and the ongoing natural history study.

Lastly, I would like to touch on our commercial portfolio.

As we have talked about for the last several years, we believe our commercialization capabilities in the U S. Our strategic strength for <unk> ability.

Asian for deliver our current product candidates if approved.

Eric Dube: As we have talked about for the last several years, we believe our commercialization capabilities in the U.S. are a strategic strength for Travere's ability to deliver our current product candidates if approved. We have demonstrated a consistent ability to identify and treat new patients living with rare kidney and liver cancer. The second quarter is another example of our team's resilience, as evidenced by the rebound in performance following the impact of the pandemic in the first quarter.

We have demonstrated a consistent ability to identify and treat new patients living with rare kidney and liver conditions.

The second quarter is another example of our team's resilience as evidenced by the rebound in performance following the impact of the pandemic in the first quarter.

We experienced year over year growth across all of our products, which speaks to the continued important role they play for patients.

Looking ahead, we continue to expect underlying demand for our products, but we do anticipate that the recently announced generic version of the original formulation of file of will have an unfavorable.

The impact on our net product sales growth in the second half of the year.

Eric Dube: We experienced year-over-year growth across all of our products, which speaks to the continued important role they play. Looking ahead, we continue to expect underlying demand for our products, but we do anticipate that the recently announced generic version of the original formulation of Phyola will have an unfavorable impact on our net product sales growth in the second half of the year. At this time, we are not in a position to reliably estimate what that impact will be.

At this time, we are not in a position to reliably estimate that we.

We'll have it what that impact will be but we plan to provide updates as we learn more about the evolution of the market. This is the scenario that has been part of our.

Planning for some time and we remain committed to the cystinuria community.

It also does not change our confidence in our plans to continue identifying and treating patients and building upon our commercialization capabilities to successfully deliver some of our centers. If approved let me now turn the call over to Noah for updates from.

The pipeline Noah.

Okay.

Thank you Eric and good afternoon, everyone.

Eric Dube: But we plan to provide updates as we learn more about the evolution of the market. This is a scenario that has been part of our business planning for some time, and we remain committed to this scenario. It also does not change our confidence in, or plans to, continue identifying and treating patients and building upon our commercialization capabilities to successfully deliver Sparsensen if approved. Let me now turn the call over to Noah for updates from the pipeline. Noah

We remain focused on developing <unk> as the potential new treatment option for people living with the Fcs.

And Iga nephropathy, and I'm pleased to report that our ongoing pivotal phase III.

Business Plex and protect studies continued to progress as planned during.

During the second quarter the <unk>.

Dependent data monitoring committee or the DMC completed its sixth scheduled meeting to assess safety in both duplex and protect the.

The DMC recommended both studies proceed.

III as plan based upon the safety review.

Noah: Thank you, Eric. And good afternoon, everyone. We remain focused on developing Sparsantan as a potential new treatment option for people living with FSGS and Ajay Nephropathy, and I'm pleased to report that our ongoing Pivotal Phase III Duplex and PROTECT studies continue to progress as planned. During the second quarter, the Independent Data Monitoring Committee, or the DMC, completed its sixth scheduled meeting to assess safety in both duplex and per text.

Looking first at FCS to pluck duplex is continuing in a blinded manner to the studies confirmatory endpoint, which will measure changes in Egfr. After 108 weeks of treatment and we continue to be pleased with its high quality conduct.

Conduct.

As many of you will recall in February we announced that the duplex study achieved its interim proteinuria endpoint.

The data showed that treatment with percentage and resulted in a 60% greater relative likelihood of achieving the <unk> partial remission of proteinuria.

Noah: The DMC recommended both studies proceed as planned based on their safety review. Looking first at FSGS, Duplex is continuing in a blinded manner to the study's confirmatory endpoint, which will measure changes in EGFR after 108 weeks of treatment. And we continue to be pleased with its high-quality conduct.

Endpoint or F PRA when compared to Irbesartan.

And overall, the safety and Tolerability profile between treatment groups in the study at the time of the analysis were generally comparable which is very encouraging.

We're working collaboratively with both FDA and EMA on the independent submission.

Weighted to ultimately deliver sports center.

Noah: As many of you will recall, in February, we announced that the Duplex study achieved its interim protein-era endpoint. The data showed that treatment with Sparsantan resulted in a 60% greater relative likelihood of achieving the FSGS partial remission of proteinuria endpoint, or FPRE, when compared to herbicartin. And overall, the safety and tolerability profile between treatment groups in the study at the time of analysis was generally comparable, which is very encouraging. We are working collaboratively with both FDA and EMA on the independent submission pathways to ultimately deliver sparsantan. In the U.S., preparations are progressing well for our upcoming Type A meeting. Our objective for the meeting is to further our dialogue from the pre-NDA meeting held earlier this year.

In the U S preparations are progressing well for our upcoming type a meeting our objective for the meeting is to further our dialogue for the pre NDA meeting held earlier. This year, we will look to align with the agency on providing additional egfr data.

Pass the ongoing study with the goal of enabling an accelerated approval submission for <unk> in the U S next year.

We look forward to continuing our constructive dialogue and providing an update in the coming months during the second quarter, we had a productive interaction with our assigned rapid share and co rapid share.

Representing the MAA for the percentage of conditional marketing authorization process in Europe.

As a result of that interaction we are continuing to move ahead with our plans to submit a CMA application by the end of this year.

Noah: We will look to align with the agency on providing additional EGFR data from the ongoing study with the goal of enabling an accelerated approval submission for FSGS in the U.S. next year. We look forward to continuing our constructive dialogue and providing an update in the coming months. During the second quarter, we had a productive interaction with our assigned rapporteur and co-rapporteur representing the EMA in the Sparcentine Conditional Marketing Authorization process in Europe.

Based upon these discussions we are.

For a standard review time in Europe.

We expect the standard review to allow us to utilize a planned clock stop to supplement our submission with the same egfr data that we're proposing to generate in the first half of 2022 for the potential U S regulatory.

Towards submission.

As you know the MAA review process is different from the U S. But we anticipate this could result in a potential approval in the first half of 2023.

Noah: As a result of that interaction, we are continuing to move ahead with our plans to submit a CMA application by the end of this year. Based upon these discussions, we are planning for a standard review time in Europe. We expect the standard review to allow us to utilize a planned clock stop to supplement our submission with the same EGFR data that we are proposing to generate in the first half of 2022 for the potential U.S. regulatory submission.

Our teams are working diligently to complete the CMA application by year end in parallel.

Well, we are also making meaningful progress on initiating enabling studies to support the CMA submission and potential pediatric approval in Europe.

Consistent with our pediatric investigation plan that was agreed to by EMA earlier. This year, we expect to initiate our open label Epic study.

Study of <unk> in children between the ages of 1 and 18 in the third quarter.

Noah: As you know, the EMA review process is different from the U.S., but we anticipate this could result in a potential approval in the first half of 2023. Our teams are working diligently to complete the CMA application by year-end.

Moving to Iga nephropathy during the second quarter, we achieved completion of patient enrollment in our phase III protect study of ups for Centene.

Achieving this milestone ahead of schedule speaks of the ex.

Cash and our clinical teams and significant unmet need in this population.

Noah: In parallel, we are also making meaningful progress on initiating and enabling studies to support the CMA submission and potential pediatric approval in Europe. Consistent with our Pediatric Investigation Plan that was agreed to by EMA earlier this year, we expect to initiate our open-label EPIC study of sparsantan in children between the ages of 1 and 18 in the third quarter. Moving to IG Nephropathy, during the second quarter, we achieved completion of patient enrollment in our Phase 3 PROTECT study of sparsantan.

There are currently no approved medicines indicated for Iga nephropathy, and non immunosuppressive steroids sparing treatment options are desperately needed given the long term tolerability concern.

Execute amongst nephrologist and patients.

Our phase III protect study is designed to determine the effect of sort of sentiment on proteinuria and renal function as compared to Irbesartan, an angiotensin receptor blocker and the current standard of care in patients with Iga nephropathy.

Proteinuria reduction in Iga nephropathy is well established as the primary treatment goal by Nephrologists and data generation of the field continues to be consistent with the recognized literature. It clearly supports the utility of proteinuria reduction and it's tied to clinically meaningful outcomes for kidney.

Noah: Achieving this milestone ahead of schedule speaks to the execution of our clinical teams and the significant unmet need in this population. There are currently no approved medicines indicated for IJ nephropathy, and non-immunosuppressive steroid-sparing treatment options are desperately needed, given the long-term tolerability concerns amongst nephrologists and patients. Our Phase 3 PROTECT study is designed to determine the effect of surfactant on proteinuria and renal function as compared to orbisortan, an angiotensin receptor blocker and a current standard of care in patients with IJ nephropathy. Protein reduction in IG nephropathy is well established as the primary treatment goal by nephrologists, and data generation in the field continues to be consistent with the recognized literature

The inspection the.

For the interim assessment and protect we'll evaluate the pre specified primary endpoint, which is the ratio of geometric mean reduction of proteinuria from baseline to 36 weeks of treatment between <unk> and Irbesartan.

Our goal for <unk> is the demonstrate.

Kidney from consistently significant and clinically meaningful response on proteinuria reduction compared to Irbesartan Ulf.

Ultimately.

We are optimistic that this interim assessment will generate a data package that will support regulatory submissions in the U S and Europe.

Noah: It clearly supports the utility of protonary reduction and its tie to clinically meaningful outcomes for kidney function. The interim assessment in PROTECT will evaluate the pre-specified primary endpoint, which is the ratio of geometric mean reduction of proteinuria from baseline to 36 weeks of treatment between sparsantan and herbicidin. Our goal for Sporcentian is to demonstrate a statistically significant and clinically meaningful response on protein area reduction compared to herbicor

Similar to our interactions with the Red.

<unk> on the duplex study, we anticipate that FDA and DMA, we'll be looking at all available data, including Egfr for determining the ability to submit for accelerated approval. There are some differences between the study designs that lead us to believe that should the protect study meet its primary endpoint.

The interim analysis, there may be a more developed data package compared to duplex to potentially support an accelerated approval submission of note. We anticipate a significant number of patients to have at least 1 year of Egfr data at the time of the interim assessment also the.

Noah: Ultimately, we are optimistic that this interim assessment will generate a data package that will support regulatory submissions in the U.S. and Europe. Similar to our interactions with the regulators on the duplex study, we anticipate that FDA and the MA will be looking at all available data, including eGFR, or determining the ability to submit for accelerated approval. There are some differences between the study designs that lead us to believe that should the PROTECT study meet its primary endpoint in interim analysis, there may be a more developed data package compared to duplex to potentially support an accelerated approval submission.

Point of study requires all patients come into the trial on maximal tolerated dose of <unk> therapy for at least 12 weeks prior to randomization and there is no washout period.

As Eric mentioned, we remain on track for top line data from the interim assessment for protect next month.

The protect we look forward to providing an update for you and then for allergy community.

Noah: Of note, we anticipate a significant number of patients to have at least one year of eGFR data at the time of the interim assessment. Also, the PROTECT study requires all patients to come into the trial on a maximal tolerated dose of ARB therapy for at least 12 weeks prior to randomization, and there is no washout period.

We do expect eliminate the disclosure as patients will be continuing on a blinded basis out the 2 years and we have a need to maintain integrity in the study through completion.

We anticipate.

<unk> provided the outcome on the interim assessment of the primary endpoint of proteinuria reduction from baseline, but we do not anticipate being able to provide egfr values.

Noah: As Eric mentioned, we remain on track for top-line data from the interim assessment for PATEK next month, and we look forward to providing an update for you and the nephrology community. We do expect limited data disclosure as patients will be continuing on a blinded basis for two years and we have a need to maintain integrity in this study through completion. We anticipate providing the outcome on the interim assessment of the primary endpoint of progenitor reduction from baseline, but we do not anticipate being able to provide EGFR values.

Lastly from the pipeline are pegged to bad news program achieved enrollment of the last patient in the highest currently planned dosing cohort.

We look forward to gaining a more comprehensive understanding of the safety and Tolerability profile of pegged the bad news and to determine if we've reached the appropriate dose to advance into a pivotal study or if the program of gain from an additional cohort to maximize the potential benefit.

We.

Today, providing either of qualitative.

Or a quantitative update before year end overall I remain pleased with our development progress we generated strong interim data supporting the profile of sort of Santana for the treatment of Iqos, yes, and we have an excellent opportunity to further establish.

Noah: Lastly, from the pipeline, our PEG-to-Batanase program achieved enrollment of the last patient in the highest currently planned dose cohort. We look forward to gaining a more comprehensive understanding of the safety and tolerability profile of PEG-to-Batanase and determining if we have reached the appropriate dose to advance into a pivotal study or if the program would benefit from an additional cohort to maximize potential benefits. We anticipate providing either a qualitative or a quantitative update before year-end.

Answers the first sentence utility with the protect study top line readout next month.

I'll now turn the call over to Peter for the commercial update Peter.

Thank you Noah.

We are very pleased with the performance from our commercial organization in the second quarter, which resulted in approximately.

Noah: Overall, I remain pleased with our development progress. We generated strong interim data supporting the profile of sparse TAN-TAN with the treatment of FSGS, and we have an excellent opportunity to further establish sparse TAN-TAN's utility with the PROTECT Study top-line readout next month. I'll now turn the call over to Peter for the commercial update.

7% organic growth over the same period last year.

The underlying strength of our business provided for us to make up some lost ground from the first quarter.

In the first half of the year was approximately 6% organic growth in line with our expectations.

Year.

During the second quarter, we continued to see demand and strong patient focus.

Some of these compliance across all of approved products.

We also experienced the normalization of our gross to net deductions, which normally occur at the beginning of each year with insurance resets.

Peter Heerma: We are very pleased with the performance of our commercial organization in the second quarter, which resulted in approximately 13% organic growth over the same period last year. The underlying strengths of our business provided for us to make up some lost ground from the first quarter and end the first half of the year with approximately 6% organic growth, in line with our expectations.

Regarding our.

During the of products <unk>.

During the quarter, we continued to see new patients initiate therapy and further demand for our sale of EC.

We experienced minimal impact from the generic version of the original formulation that entered the market during this quarter.

Mentioned earlier, we anticipate.

The sale will be an unfavorable impact on play of low revenues in the second half of the year.

Peter Heerma: We continue to see demand and strong patient focus, although some patient compliance across all approved products. We also experienced the normalization of our growth methodology, which normally occurs at the beginning of each year for insurance reasons regarding our trial of drugs. During the quarter, we continue to see new patients initiate therapy and further demand for our Puyallup EC. We experienced minimal impact from the generic version of the original formulation that entered the market during this quarter. And, as I mentioned earlier, we anticipate there will be an unfavorable impact on Payola revenues in the second half of the year.

Despite this we currently anticipate being able to continue identify and through the new patients for the foreseeable future.

Is it portfolio is providing important treatment choice for pediatric typical of juice.

And we continue to expect gross through the balance of the year.

Within the pediatric Hepatology space, we were pleased to see the recent approval of <unk> building. The first approved treatment of pruritus in all subtypes of <unk>.

And for our limit the co promotion agreement.

The <unk>.

We look forward to leveraging our established expertise to help deliver this much needed new treatment options for people living with this rare athletic condition.

We are also optimistic that our work on these loans will provide additional opportunities to engage with those.

Specialists that treat with gold zone.

Overall.

Peter Heerma: Despite this, we currently anticipate being able to continue identifying and treating new patients for the foreseeable future. The BioAgent Portfolio is providing an important treatment choice for pediatric hepatologists, and we continue to expect growth through the balance of the year. Within the pediatric hepatology space, we were pleased to see the recent approval of Alvarez-Milva, the First Approved Treatment of Paritis in All Subtypes of P4.

I am proud of our commercial progress in the first half of the year.

We have maintained the focus on identifying and treating new patients and further strengthening our capabilities.

We continue to ready our organization by building upon the.

Foundational pre commercialization work to support plus income in most of <unk> and Iga nephropathy with the goal of successful for loans in the U S. As early as next year.

I'd like to turn the call over to Laura for the financial update.

Laura.

For the second quarter of 2021, we reported net product sales of $54.6 million from our commercial portfolio compared to $48.4 million for the same period in 2020.

Peter Heerma: As part of our limited co-promotion agreement with Alvarejo, we look forward to leveraging our established expertise to help deliver these much needed new treatment options for people living with this rare hepatic condition. We are also optimistic that our work on this launch will provide additional opportunities to engage with those specialists that treat full-blown Overall, I am proud of our commercial progress in the first half of the year. We have maintained a focus on identifying and treating new patients and further strengthening our capability.

We reported a GAAP net loss of $39 million for the second quarter of 2021.

After adjusting for non cash expenses and income tax we reported a non-GAAP net loss of $23.3 million for the second quarter of 2021.

On a GAAP basis, R&D expenses were $51.8 million for the second quarter of 2021 the increase.

Compared.

For 2020 is largely attributable to increased patient enrollment in the ongoing studies of spar setting as well as the advancement of the pegged to bad News program and classical H C U.

Peter Heerma: We continue to ready our organization by building upon the foundational pre-commercialization work to support Parcenton in both FITS and IGA in the proper way, with the goal of a successful first launch in the U.S. as early as next year. I'd like to turn the call over to Laura now for the financial update.

On an adjusted basis R&D expenses were $48.7 million for the second quarter of 2021.

Relevant.

<unk> non cash expenses for the second quarter included $3.1 million of stock based compensation and amortization.

Laura: For the second quarter of 2021, we reported net product sales of $54.6 million from our commercial portfolio compared to $48.4 million for the same period in 2020. We reported a gap net loss of $39 million for the second quarter of 2021. After adjusting for non-cash expenses and income tax, we reported a non-GAAP net loss of $23.3 million for the second quarter of 2021. On a gap basis, R&D expenses were $51.8 million for the second quarter of 2021.

On a GAAP basis, selling general and administrative expenses for the second quarter were $35 million and is comparable to the same period in 2020.

On an adjusted basis.

SG&A expenses for the second quarter were $24 million.

Significant noncash adjustments for the quarter consisted of $11 million in stock based compensation and depreciation and amortization for.

For the balance of the year, we expect gradual and modest increases in our operating expenses.

Primarily driven by continued clinical development of programs and activity to support potential launches of the first sentence.

Our financial Foundation to support this activity remains strong.

For the second quarter, we were nearly neutral on cash use as a result of receiving final tax refunds related to the care.

Laura: The increase compared to 2020 is largely attributable to increased patient enrollment in the ongoing studies of Sparsantan, as well as advancement of the PEG-to-Batinase program in classical HCU. On an adjusted basis, R&D expenses were $48.7 million for the second quarter of 2021. Relevant non-cash expenses for the second quarter included $3.1 million of stock-based compensation and amortization. On a gap basis, selling general and administrative expenses for the second quarter were $35 million, which is comparable to the same period in 2020. On an adjusted basis, SG&A expenses for the second quarter were $24 million.

Third the act, which offset our operating cash use.

Not including additional business development, our total cash balance of $522.8 million at the end of the quarter is expected to support our current operations into 2023.

It takes into consideration potential impact of the generic version of sales.

As well as investments as per cent and prelaunch and early launch activities and advancing the pig Tibetan Ace program.

I'll now hand, the call back over to Eric for his closing comments Eric.

Thank you Laura and the first half of this year, we generated further evidence to support the value of that sport.

The old can bring to patients and 2 of organization I'm incredibly proud of our team's continued execution of our landmark studies in F. S. G. Aspinall Iga nephropathy and remain excited about our path of hugs, we remain confident that we want to ultimately be in a position to deliver sports center of the potential new treatment standard for.

Laura: Significant non-cash adjustments for the quarter consisted of $11 million in stock-based compensation and depreciation and amortization. For the balance of the year, we expect gradual and modest increases in our operating expenses, primarily driven by continued clinical development of programs and activity to support potential launches of our product. Our financial foundation to support this activity remains strong. For the second quarter, we were nearly neutral on cash use as a result of receiving final tax refunds related to the CARES Act, which offset our operating cash use.

Patients with the F. S geos in the U S and we look forward to continuing our path for patients in Europe by submitting our CMA application by the end of this year.

Furthermore, we have an exciting opportunity ahead of us with the protect results coming next month, which have the potential to build upon the growing evidence supporting sports Center is the first.

Non immunosuppressive innovation in decades for patients living with Iga nephropathy.

Through the balance of this year, we will remain focused on the priorities that will enable us to deliver sports center and the rest of our pipeline of patients who desperately need new treatment options. Let me now turn the call over to Chris for Q&A Kris.

Laura: Not including additional business development, our total cash balance of $522.8 million at the end of the quarter is expected to support our current operations into 2023. This takes into consideration the potential impact of the generic version of Psyola as well as investments in sparsentine prelaunch and early launch activities and advancing the PEG-tobatenase program. I will now hand the call back over to Eric for his closing comments.

Great. Thanks, Eric drunk can we please go ahead and open up the line for Q&A. Please.

Ladies and gentlemen, if you have a question at this time. Please press the star and the number 1 key on your Touchtone telephone. If your question has been answered or you wish to remove yourself from the queue. Please press the pound key in your for.

First question comes from Joseph Schwartz with <unk> Leerink. Your line is open.

Hi, everyone. Thanks, so much I was hoping to gain a better understanding about your expectation for an unfavorable impact on the Fiola French franchise from the recent approval of the generic for.

Eric Dube: Thank you, Laura. In the first half of this year, we generated further evidence to support the value that Sparsantan can bring to patients and to our organization. I'm incredibly proud of our team's continued execution of our landmark studies in FSGS and IJ nephropathy and remain excited about our path. We remain confident that we will ultimately be in a position to deliver Sparcentin as a potential new treatment standard for patients with FSGS in the U.S., and we look forward to continuing our journey for patients in Europe by submitting our CMA application by the end of this year.

For the first Gen formulation is the unfavorable impact that you expect just from a decrease in sales.

Of your branded first generation formulation or do you expect that patients will actually switched back from people that you see to the generic.

To the first Gen and how much of your feel of franchise is already convert.

You see.

And do you have any color commentary that you can offer that could help us model the low revenue over the next 12 months on any changes in prescription patterns that you've detected so far thank you.

Eric Dube: Furthermore, we have an exciting opportunity ahead of us with the PROTECT results coming next month, which have the potential to build upon the growing evidence supporting sparsentine as the first non-immunosuppressive innovation in decades for patients living with IgA nephropathy.

Thanks, so much for the questions I'll start out by saying that at this time, it's just really difficult for.

For us to project reliably what erosion might take place given that there's been very little time, and we've actually seen very little uptick of the generic since it's been available that said, we do believe that things will evolve.

Christopher Cline: Through the balance of this year, we will remain focused on the priorities that will enable us to deliver Sparsentin and the rest of our pipeline to patients who desperately need new treatment options. I will now turn the call over to Chris for Q&A.

And I'll ask Peter to talk a little bit about how that might evolve in.

<unk> of our business as well as your question around the split between <unk> and file what you see.

Christopher Cline: Great. Thanks, Eric. Jerome, can we please go ahead and open up the line for Q&A, please? Ladies and gentlemen, if you have a question at this time, please press the star and then the number one key on your touchtone telephone. If your question has been answered or you wish to remove yourself from the queue, please press the pound key. And your first question comes from Joseph Schwartz on behalf of SVB Laurent.

Yes, Thanks, Eric.

And the other things for your question I mean, we knew that at a certain time, we could be facing generic competition. So in that respect we have been plenty for.

For the scenario.

The first of all of the year, we have been very pleased with our continued performance both in identifying the patients as well as well as allowing services for those patients.

Hum.

All of the treatments already and to repay those patients. So the aerospace we have seen limited impacts on the floor.

Joseph Patrick Schwartz: Your line is open. Hi everyone, thanks so much. I was hoping to gain a better understanding about your expectation for an unfavorable impact on the Theola franchise from the recent approval of a generic for the first gen formulation. Is the unfavorable impact that you expect just from a decrease in sales of your branded first generation formulation or do you expect that patients will actually switch back from Theola EC to the generic to the first gen and how much of your Theola franchise has already converted to EC and do you have any colored commentary that you can offer that could help us model Theola revenue over the next 12 months on any changes in prescription patterns that you've detected so far?

That doesn't mean that there won't be on.

And then the second half of the year, but it's early days. So I think we have to better understand how the dynamic may play out.

Also with regards to your question with regards to the original formulation and the feeling that you see right now we have less than 20% of the patients that are still on the original formulation.

And.

Like I said, we have to get a better understanding on.

Of the dynamics with regards to formulary and how we'll be adopting the new generic version.

But we remain the of articles.

Our ability and the infrastructure that we have built over the last 7 years most of the identified new patients as well as.

In fact in providing support for those patients that are on the program. So the.

Is there can be seen and we will be closely monitoring the impact of the latest time point of view will be of additionally.

<unk> of what the impact for you.

Thank you very much that's super helpful. And I was wondering also if you could talk about how you are preparing.

Joseph Patrick Schwartz: Thank you, Joe, thanks so much for the questions. I'll start out by saying that at this time, it's just really difficult for us to project reliably what erosion might take place, given that there's been very little time, and we've actually seen very little uptick of the generic since it's been available. That said, we do believe that things will evolve, and I'll ask Peter to talk a little bit about how that might evolve and impact our business, as well as your question about the split between FIOA and FIBA.

In your upcoming type a meeting with the FDA in order to make your interactions is persuasive as possible and hesitance meetings and schedule of yet when you update investors. After it occurs or you received the minutes.

Bring for you about that I was on mute so.

Joe Yes.

We do have the meeting schedule and it has not yet occurred so.

I'll ask bill to talk a bit about the preparation what I can say is that we certainly are.

Peter Heerma: And Joe, thanks for your question. I mean, we knew that at a certain time we could be facing generic competition. So in that respect, we have been planning for this scenario. In the first half of the year, we have been very pleased with our continued performance, both in identifying new patients as well as providing services for those patients that are out in treatment already and retaining those patients. So to Eric's point, we have seen limited impact so far.

Reinforcing we believe FDA understands the high unmet need within the space. So.

Very much Bill will talk about what our goals on how they are preparing.

Certainly the.

The process of preparation begins with submission of a briefing book and outlining our position going into the meeting and providing the agency with detailed information about our.

So on moving forward coming out of the pre NDA discussions 1 of the the.

Peter Heerma: That doesn't mean that there won't be an impact in the second half of the year, but it's early days. So I think we have to better understand how the dynamics may play out. Also, with regard to your question, with regard to the original formulation and the PHA-OLA-EC, right now, we have less than 20% of the patients that are still in the original formulation. But, like I said, we have to get a better understanding of the dynamics with regard to formulary and how formularies will be adopting the new generic version.

The specific ask from the agency was around just give us the specifics of your proposal for a second look at Egfr and the first half of next year, how would that work specifically give us the details.

Plans around the statistical analysis and.

Efforts made in how are you preserving the integrity of the study given that this is an ongoing study that runs out for 2 years for each of the patients. So that's been the bulk of the preparation and we look forward to having those discussions with the agency in this quarter.

Peter Heerma: We remain rather confident in our ability and the infrastructure that we have built over the last seven years, especially in identifying new patients as well as in providing support for those patients that are on the product. So it's yet to be seen, and we will be closely monitoring the impact, and at a later point, we will give additional perspective on what the impact may be. Thanks very much. That's great.

Thanks, Bill and just to close out on the other part of your question Joe We.

We will plan to provide a public disclosure on these regulatory interactions. Once we receive written minutes just to make sure that we're in full alignment and understand the fda's thinking after the meeting.

Excellent, Thanks, again and best wishes.

Thank you.

Joseph Patrick Schwartz: Thank you very much. That's super helpful.

And of your next question comes from Carter Gould of with Barclays. Your line's open.

Joseph Patrick Schwartz: And I was wondering also if you could talk about how you're preparing for your upcoming Type A meeting with the FDA in order to make your interactions as persuasive as possible. And has this meeting been scheduled yet? Will you update investors after it occurs, or will you receive them in advance? Sorry about that; I was on mute.

Yeah, Hi, this is Justin on for Carter. Thanks for taking on a question first 1 on protect of sort of understanding that.

Need to maintain the integrity of the study, but given that youre going to have a substantial amount of patients for the year's.

Worth of.

William E. Rote: So Joe, yes, we do have the meeting scheduled, and it has not yet taken place. So I'll ask Bill to talk a bit about the preparation. What I can say is that we certainly support and believe FDA understands the high unmet need within this space. So, very much, Bill will talk about what our goals are and how they're preparing. Certainly, Eric. The process of preparation begins with submission of a briefing book and outlining our positions going into the meeting and providing the agency with detailed information about our plans moving forward.

Egfr data on when it reads out next month can you characterize how much freedom of Youre going to have the potentially give qualitative messaging around those egfr trends and sort of if you're thinking there has changed at all with your ongoing discussions with FDA.

Sure.

Justin Thanks, so much for the question.

I would say that we are aiming to be as consistent as possible with the disclosure from the duplex interim.

And since then we've learned quite a bit from the FDA and our interactions on duplex and believe that we may be able to provide some type of qualitative update on what we're seeing that that may be helpful for.

William E. Rote: Coming out of the pre-NDA discussions, one of the specific asks from the agency was around just giving us the specifics of your proposal for a second look at EGFR in the first half of next year. How would that work specifically?

To understand the status of the trial, but ultimately that's going to be based on the data as well as any guidance that FDA provides on our disclosure practice just to make sure that we're in alignment with how they view the maintenance of integrity of the on.

William E. Rote: Please give us the details around the statistical analysis and efforts made, and how are you preserving the integrity of the study given that this is an ongoing study that runs out two years for each of the patients? So that's been the bulk of the preparation, and we look forward to having those discussions with the agency this quarter. Thanks, Bill. And just to close out on the other part of your question, Joe, we will plan to provide a public disclosure on these regulatory interactions once we receive written minutes, just to make sure that we're in full alignment and understand the FDA's thinking.

Going trial.

Okay Awesome. Thank you and then 1 quick 1 on.

So ex just given that you'll be filing in the in the EU and the EU first does that sort of.

Was there any additional information that we shared or that you plan to share with them ahead of the filing or was that decision based a lot around the sort of mid reviews stoppage meeting that should be occurring next year.

So I will turn the call.

On do question over to Bill.

Yes, so the EMEA saw the same interim data package that we provided to the FDA and Additionally, we made them aware of the progress of our discussions with the FDA and the plans to share additional egfr.

William E. Rote: Excellent. Thanks again and best wishes. Thank you. And your next question comes from Carter Gould with Barclays. Your line is open. Yeah, hi, this is Justin on behalf of Carter. Thanks for taking our question. The first one on protection is sort of understanding that you need to maintain the integrity of the study.

All of that Peter.

In the first half of next year.

The EMA was interested and also seeing that Egfr data and as you.

Justin: But given that you're going to have a substantial amount of patience for the year's worth of lessons,

Noah: EGFR data, when it comes out next month, can you characterize how much freedom you're going to have to potentially...

Alluded to there's the clock stoppage period.

The times out appropriately.

<unk>.

Procedurally, we can add those information those data and information.

Justin: have to potentially give qualitative messaging around those EGFR trends and sort of if you're thinking anything has changed at all with your ongoing discussions with FDA. Sure. So, Justin, thanks so much for the question.

2 of the review at that point in time.

Great. Thanks, so much and congrats on all of the progress.

Thank you.

Your next question comes from Lisa <unk> with Evercore ISI.

Noah: I'd say that, you know, we are aiming to be as consistent as possible with the disclosure from the duplex interim. And, you know, since then, though, we've learned quite a bit from the FDA and our interactions with duplex and believe that we may be able to provide some type of qualitative update on what we're seeing that may be helpful to understand the status of the trial. But ultimately, that's going to be based on the data as well as any guidance that FDA provides on our disclosure practice, just to make sure that we're in alignment with how they view the maintenance of integrity of the ongoing trial.

ISI Your line is open.

Hi, Thanks for taking the questions and a good quarter can you comment on the.

On the possibility of the generic I'll, let you see and what.

What implications are there if you do get any patents for that can you walk us through that scenario.

Sure.

Why don't I take that 1 Lisa.

Is the possibility that there is of generic for.

File EC it's something that we will continue to monitor but were not aware of such activity imminently, but again it certainly is a possibility.

Noah: Okay, awesome. Thank you. And then one quick one on duplex, just given that you'll be filing in the EU in the EU first, is that sort of, you know, was there any additional information that was shared? Or do you plan to share with them ahead of that filing? Or was that decision based a lot on the sort of mid-review stoppage meeting that should be occurring next year?

We continue.

To be in the process of engaging with the patent office for a final the EC patent and if that is granted then certainly that may allow.

You know for continued exclusivity of that newer formulation.

At this point given that that has not yet been granted.

I would suggest considering.

Any type of patent coverage as an upside to that existing business.

Okay, great. Thanks.

William E. Rote: So I will turn that question over to Bill. Yeah, so the EMA saw the same interim data package that we provided to the FDA. Additionally, we made them aware of the progress of our discussions with the FDA and the plans to share additional EGFR data in the first half of next year. The EMA was interested in also seeing that EGFR data. And as you alluded to, there's a clock stoppage period that times out appropriately where, procedurally, we can add that information or those data, that information to the review at that point. Great. Thanks so much and congrats on all the progress.

And then.

For our protect I'm really excited to see the data coming up and.

I just wanted to ask.

I understand the point about having like a period of maximum tolerated center of care. You know at 12 weeks ahead of time of and how that will help.

Study.

Granted it's an F. S. Yes, you know there was sort of the something that was the proxy for that of my view, which is there was an 8 week treatment period for.

Of the people on placebo with and crossover.

So what what are we to make of that because there was actually a pretty.

Lengthy dip in Egfr, which took all of it looked like it took about 40 weeks to recover.

Can you maybe talk about sort of how you think about that observation vis vis the run in period.

William E. Rote: Thank you. Your next question comes from Liisa Bayko with Evercore ISI. Your line is open.

Sure and I think.

Lisa just to make sure that I'm clear on the question you are referring on that that 8 week crossover in the Egfr.

Liisa Ann Bayko: Hi, thanks for taking the questions and for a good quarter. Can you comment on the possibility of a generic FIOLA EC and what implications there are if you do get any patents for that? Can you walk us through that scenario? Sure. Why don't I take that one, Liisa?

Acute.

That is from the duet study.

Yes, yes, okay, great. So no what do you want to take this question.

Sure.

It's a great question, Lisa just reminding that the design was different in the sense that we had 3 doses. So we started the 200.400 to 800.

Eric Dube: There is a possibility that there is a generic for FIOA-EC. It's something that we will continue to monitor, but we're not aware of any such activity imminently. But again, it certainly is a possibility. We continue to be in the process of engaging with the Patent Office for the FIOA-EC patent. And if that is granted, then certainly that may allow for continued exclusivity of that newer formulation. At this point, given that that has not yet been granted, I would suggest considering any type of patent coverage as an upside to that existing.

So some of those patients coming across with the lower doses may have impacted.

Of that dip and.

I think having.

The tolerated east.

And then going right into all of them.

Again right into the.

The irbesartan.

Believe me provided.

You know the ability to show in a more a clearer way addition of DRA on topic of angiotensin blockade. So it's a slightly different.

To answer your question.

Sorry, I'm on how does it how does the dose related I didn't I didn't quite make the link well it looks like you're saying remember yes.

Liisa Ann Bayko: Okay, great, thanks. And then for PROTECT, I'm really excited to see the data coming out. And I just wanted to ask, I understand the point about having, like, a period of maximum tolerated standard of care, you know, 12 weeks ahead of time and how that will help, [inaudible] So what are we to make of that? Because there was actually a pretty lengthy dip in EGFR, which looked like it took about 40 weeks to recover. Can you maybe talk about sort of how you think about that observation vis-a-vis the run-in period?

So when you add it's not just a matter of going from.

From the <unk> 10.

Sorry for Airbus from angiotensin blockade to Irbesartan.

It was going from dose, let's say of 200 for Centene or 400 up to.

Higher doses when they went into the the crossover.

I don't think there is an impact there of change the doses for content. In addition to the right yeah.

So I think none of what Youre, saying.

The variability of patient.

Patients coming into the duet study as well as the variability across the different dose levels youre going to have.

Noah: Sure, and I think, Liisa, just to make sure that I'm clear on the question, you're referring to that eight-week crossover and the EGFR acute dip is from the DUET study. Yes. Yeah. Okay. Great. So, Noah, do you want to take this question? Sure. It's a great question, Liisa.

You introduce more variability and looking at what purely sports centered on the Endothelin blockade can do on top of Max tolerated well now go on remember the doses. We're like you started at 200, and then you might have gone to 400.

800, and so I guess that took some time and that does it probably lengthened out that hemodynamic effect right. The cute metonymic, Yeah. I think that's I think the that's what I'm, saying exactly okay. Okay. And then just last question for me for almost 5.8.

Noah: Just recalling that the duet design was different in the sense that we had three doses, so we started at 200, 400, and 800. So some of those patients coming across with the lower doses may have impacted that dip. And you know, here I think, you know, having maximally tolerated ACE-ARB and then going right into, again, right into the herbicartin, we believe may provide, you know, the ability to show in a more clear way the addition of ERA on top of angiotensin blockade. So it's a slightly different design. Thank you.

What are you looking for in the data.

So that's the product we don't think about it as much but you know you kind of mentioned you're going to be looking for the.

The highest dose to determining the I guess on yet another dose cohort what exactly you're going to be looking at them. If you could just give us the.

Understanding there. Thanks sure. Thanks, Lisa for that question because we are we are really excited.

Fitted about this program as well on I'll ask bill to talk a bit about what we're planning to evaluate in that phase 1.2.

Certainly with any phase 1.2 study and this is the first in human study for this molecule.

Liisa Ann Bayko: I hope that answers your question. Sorry, how does the dose relate? I didn't quite understand the link.

The primary is of course safety and Tolerability beyond that we're.

Noah: Well, it was, remember, yes, so in duet, it's not just a matter of going from sparsantan, sorry, from angiotensin blockade to herbicartin. It was going from a dose, let's say, of 200 sparsantan or 400 up to higher doses when they went into the crossover period. So you're saying there's an impact there of changing the dose of sparsantan in addition to, right? Yeah, so I think, Noah, what you're saying is the variability of patients coming into the duet study as well as the variability across the different dose levels, you're gonna have to introduce more variability in looking at what purely sparsantan and the endothelin blockade can do on top of max tolerated.

So looking and I think the heart of your question is really looking at from an efficacy readout on the biochemical markers what are you seeing changing.

On a dose dependent basis within these patients over time in response to repeated administrations of.

Of pegged the Baton Ace.

For.

Foremost in those measurements and there aren't many is certainly homocysteine concentration in the plasma and these patients are troubled by very high almost sustain at very low matteini.

And so normalizing that mix in that patient population is.

So what.

Degree can we lower these very high levels of AUM of sustaining their plasma is part of what we're looking at as long as the the variability in the response between patients and with in patients and the durability of the response over time.

Noah: Yeah, and as I remember, the doses were, like, you started at 200, and then you might've gone to 400, 800. So I guess that took some time, and that just probably lengthened that hemodynamic effect, right? The acute hemodynamic effect.

Ultimately.

In future.

Studies, 1 of the things that's going to be an important piece for us is looking at.

Liisa Ann Bayko: Yeah, I think that's exactly what I'm saying. Okay, good. And then just one last question from me. For 058, what are you looking for in the data? Because that's a product we don't think about as much, but, you know, you kind of mentioned you're gonna be looking for the highest dose to determine if you need to get another dose cohort. What exactly are you gonna be looking at? If you could just give us the understanding,

The ability to predict clinical benefit for these individuals and the long term, but also in the short term.

Is there enough of a lowering of plasma homocysteine that theres some liberalization that.

Be allowed in their diet.

These patients are forced to eat a very low protein that's on.

In poor diet that is quite unpalatable and very difficult to adhere to.

William E. Rote: Sure. Thanks, Liisa, for that question, because we are really excited about this program as well. And I'll ask Bill to talk a bit about what we're planning to evaluate in that phase. Certainly, with any Phase I, II study, and this is the first human study for this molecule, the primary is, of course, safety and tolerability. Beyond that, we're also looking, and I think the heart of your question is really looking at, from an efficacy readout on the biochemical markers, what are you seeing changing on a dose-dependent basis within these patients over time in response to repeated administrations of pegtobatinase?

Regardless of whether their children or adults and if we're able to lower.

Home of sustained to the point where.

That might that can be ameliorated, even in part that would be huge at the from the patient perspective and quality of life aspects.

Okay, Great. That's really helpful. Thanks, a lot for answering my question.

Lisa.

Your next question comes from Tim Lugo with William Blair.

Okay.

Thanks for taking the question.

I guess following up on the home of 15 drops.

Expected in the tech the bad news.

William E. Rote: foremost in those measurements, and there are many, is certainly homocysteine concentration in the plasma. These patients are troubled by very high homocysteine and very low methionine. And so normalizing that mix in that patient population is, you know, to what degree can we lower these very high levels of homocysteine in their plasma is part of what we're looking at, as well as the variability in the response between patients and within patients, and the durability of their response over time, ultimately, in future studies, one of the things that's going to be an important piece for us is looking at the ability to predict clinical benefit for these individuals in the long-term, but also in the short-term, is there enough of a lowering of plasma homocysteine that there's some liberalization that might be allowed in their diet?

Data by year end how much.

How much.

How much of a drop is going to kind of lead to the cognitive function and maybe some of the ocular health.

Endpoints, you're looking at is there.

Can you just give us a sense of what the natural history data and maybe for Jeff.

Sure Tim I'll give a high level and then have bill turnover I mean, there's been some.

Your line.

Early data.

Linking homocysteine levels and really trying to get what is considered under.

Under the threshold of 150 for for these patients which is incredibly challenging for many patients, but there is a link there, but I'll ask bill to talk about half.

The work that we're doing.

Doing all of the natural history study to really help in bolstering our understanding of that link.

William E. Rote: These patients are forced to eat a very low-protein methionine-poor diet that is quite unpalatable and very difficult to adhere to, regardless whether they're children or adults. If we're able to lower homocysteine to the point where that can be ameliorated, even in part, that would be huge from the patient perspective and quality of life.

Yeah. Thanks for the question, Tim on and it's a really challenging question because of what's out there in the literature are retrospective studies that look at essentially treated and untreated individuals and the treated individuals don't.

Some huge drop in home of 16, but theyre certainly better off than those that are not diagnosed until they're older in that comparison, you do see differences.

Liisa Ann Bayko: Okay, great. That's really helpful. Thanks a lot for answering my question. Certainly, sir. Your next question comes from Team Lugo with William Blair. Your line is open.

In cognitive development in IQ scores and rates of thrombosis and rates of lens dislocation.

Timothy Francis Lugo: Thanks for taking the question.

Eric Dube: I guess, following up on the homocysteine drops expected in the peg-to-batonase data by year-end, how much of a drop is going to kind of lead to cognitive function and maybe some of the ocular health? You know, the endpoints you're looking at, is there, you know, can you just give us a sense of what the natural history data maybe suggests? Sure, Tim, I'll give you a high level and then have Bill turn it over.

Et cetera, the <unk>.

And.

I think that you're asking is how much homocysteine reduction do you need to see in order to prove.

Prevent.

The future clinical events because of treating a patient today is not going to do anything about historical changes that have already occurred and cognitive changes that have already taken.

William E. Rote: I mean, there's been some early data linking homocysteine levels and really trying to get what is considered under the threshold of 100 or 50 for these patients, which is incredibly challenging for many patients, but there is a link there. But I'll ask Bill to talk about how the work that we're doing on the National History Study is really helping in bolstering our understanding of that. Yeah, thanks for the question, Tim.

Place of probably the most difficult to reverse.

But that's part of the program going forward and it's.

There is a certain element of clinical investigation here, we know that lower is better and we know that the treatment guidelines in the past had been to try and get these patients below 100 micro molar.

But normal is down in the teens, so are we able to drive it lower.

William E. Rote: And it's a really challenging question, because what's out there in the literature are retrospective studies that look at essentially treated and untreated individuals. And the treated individuals don't see a huge drop in homocysteine, but they're certainly better off than those that are, you know, not diagnosed until they're older. In that comparison, you do see differences in cognitive development, in IQ scores, in rates of thrombosis, in rates of lens dislocation, etc. The question, I think, that you're asking is, how much homocysteine reduction do you need to see in order to prevent future clinical events?

And.

Keep it lower and if so what's the benefit from there and we'll be working on that based on.

All of the aspects of data and won't prime among them is the natural history study.

Okay. Thanks.

And.

I guess going back to as far as centre in okay.

Following the interactions with EMA.

I guess broadly discuss a bit about what 1 of the.

For the data effectively the same as the data you took the the FDA was there.

For the changes in the presentation.

William E. Rote: Because treating a patient today is not going to do anything about historical changes that have already occurred, and cognitive changes that have already taken place are probably the most difficult to reverse. But that's part of the program going forward. And it's, You know, there's a certain element of clinical investigation here. We know that lower is better. And we know that the treatment guidelines in the past have been to try and get these patients below a hundred micromolar, but normal is down in the teens. So are we able to drive it lower and keep it lower? And if so, what's the benefit from there?

Or is it merely just the.

The.

Of the clock stoppage what's the.

Our current is there.

Our submission in and the timing of the submission.

The.

It seems like on the line up more with the interim look you'll take in 2022.

The any for US I guess, it's just the EMA is looking at the different leaving the FDA or is it just merely of more of a function of the timing of the file.

Bill do you want to take this 1.

Certainly I think the the.

The first part of your question I can answer easily they saw essentially the same data package.

They both saw the full interim data cut and it was presented the same way, but the different agencies have different processes.

William E. Rote: And we'll be working on that based on all the aspects of data, and one prime among them.

So the filing process the review process.

William E. Rote: Prime among them is the Natural History Study.

Timothy Francis Lugo: Okay, thank you for that.

They are different and the EMEA team had the advantage of knowing the.

Eric Dube: I'm just going back to Sparse Fenton.

Timothy Francis Lugo: Sparse Fenton You know, following the interactions with EMA, I guess broadly discuss a bit about what the data are. Was the data effectively the same as the data you took to the FDA? Was there any change in the presentation, or is it merely just the... [inaudible] 2, or is, I guess, the EMA looking at this differently than the FDA, or is it just merely more of a function of the timing of the filing?

On the outcome and the of the discussions we had.

We made that known to them. So that they were completely informed about our intentions to our our proposal with the FDA to have the additional data in the first half of next year and then.

So that shapes your thinking as well.

And made it.

Feasible for us to align on a proposal where those data would be provided as supplementary information during the clock stop.

Timothy Francis Lugo: Certainly, I think that the first part of your question is easy to answer: they saw essentially the same data. They both saw the full interim data cut, and it was presented the same way. But the different agencies have different processes. And so the filing process, the review process, they are different, and the EMA team had the advantage of...

Okay.

Understood and kind.

I guess the quickly.

To protect I'd love to hear your thoughts around.

Kind of the.

The competitive phase 2 data that we have seen I guess relatively recently.

From some of the larger players out there.

Sure I'll ask Noah to give some thoughts on on the.

Eric Dube: The outcome of the discussions we had with the FDA, we decided that.

The other.

Treatments being developed.

William E. Rote: , David Kaul, , , , , , , , , , , , , ,

Yes.

Timothy Francis Lugo: Okay, understood. And can I, I guess, just quickly, you know, how to protect yourself? I'd love to hear your thoughts around kind of the competitive phase two data that we have seen, I guess, relatively recently, from some of the larger players out there.

2 questions. Please.

What's exciting is there is number of.

The studies ongoing in this deal and it really does validate.

Sorry, there is the number of studies going on can you hear me now I apologize, yes, we can.

On here.

Sorry, Tim.

Noah: Sure, I'll ask Noah to give some thoughts on the other treatments being developed. Sorry, there are a number of studies going on. Can you hear me now?

So theres a number of ongoing studies as you pointed out I think the key is 2 points number 1.

Most of the work that's being done is currently in the immune suppressive ISP camp and even even some of the lower dose steroids are still.

Noah: I apologize. Yeah, we can hear you. Oh, sorry. So there are a number of ongoing studies, as you pointed out. I think the key is two points. Number one, most of the work that's being done is currently in the immune suppressors, or ISP camp, and even some of the lower dose steroids are still within that realm. And so I think one of the strengths of Sporphentan being a non-immune suppressive therapy is that I think there's still a huge opportunity there for Sporphentan and other non-immune suppressive therapies.

<unk> within that that realm, and so I think 1 of the just the strength of us for center and being on the on immune suppressive therapy.

I think there's still a huge opportunity there.

For Sports Center on Anatomy Express of therapies, you know because of those steroid and it means for us of treatments has the potential for tolerability concerns the long term.

On the issue so I think that those mechanisms need to really be borne out from a safety standpoint long term I think is for sinton is really has the ability with its efficacy and safety profile to really be a standard of care.

Noah: Because those steroid and immune suppressive treatments have the potential for tolerability concerns and long-term safety issues. So I think those mechanisms need to really be borne out from a safety standpoint over the long term. I think Sporphentan really has the ability, with its efficacy and safety profile, to really be a standard of care. You know, treatment

Treatment and I think the so I think that's the main the main for us the other pieces.

We don't see any reason why we've seen.

You used the of course that then we've used it on top of immune suppressive therapy, and still seen an effect of sports centered on incrementally. So we don't see a reason why the first sense it could be used in the complementary manner as well on top of those of those treatments. So it doesn't really change.

Noah: And I think the, so I think that's the main thrust. The other piece is that we don't see any reason why, and we've seen the use of Sporphentan. We've used it on top of immune suppressive therapy and still seen an effect of Sporphentan gradually. So we don't see a reason why Sporphentan could be used in a complementary manner as well on top of those treatments. So, you know, it doesn't really change our approach. We're really pretty far in the lead here.

Or our approach, where we're really pretty far in the in the lead here.

But again, it's good for patients and we think these different mechanisms will ultimately hopefully be complimentary to each other.

Understood. Thank you.

Thanks, Tim.

Your next question comes from Greg Harrison.

Bank of America your line's open.

Noah: But again, it's good for patients, and we think these different mechanisms will, ultimately, hopefully be complementary to each other. Understand? Thank you. Your next question comes from Greg Harrison with Bank of America. Your line is open.

Hey, guys. Thanks for taking the question on another 1 on peg to the Bad news just wanted to get your thoughts on the.

The commercial potential that you see for this asset and if you can talk a little bit about how it fits into.

On to your portfolio and what considerations you would take into account.

Greg Harrison: Hey guys, thanks for taking the question. Another one on pegging that mace, just wanted to get your thoughts on the commercial potential that you see for this asset and if you could talk a little bit about how it fits into your portfolio and what considerations you would take into account when it comes to future BD activity. I know the focus is kind of sparse now, but just wanted to get your sense of what may happen in the future as far as BD is concerned and what size of deals you'd consider.

When it comes to feature of BD activity I know you know the focus of this kind of a square center now but.

Just wanted to get your sense of them.

What may happen in the future as far as BD and what size.

As of the deals you would consider.

Sure great. Thanks, so much for the question so with regard to the commercial potential in Costco home assistant here. If we look at the U S and Europe Theres about 3000.3500 patients that are that we believe for currently addressable.

Eric Dube: Sure, Greg, thanks so much for the question. So, with regard to the commercial potential of classical homocysteinuria, if we look at the US and Europe, there are about 3,000, 3,500 patients that we believe are currently being addressed. And we think that that underestimates the real opportunity to help these patients, given that many of them go undiagnosed for years despite having homocysteine. Home Assisting Urea should be part of the newborn screening in many.

And we think that that.

Underestimate.

It's the the real opportunity to help these patients given that <unk>.

Many of them go on diagnosed for for years, despite having home assisting home assistant urea as part of the newborn screening in many states.

And that's just because of the methodology the skus oftentimes these.

Go undetected and so we think through increased awareness and the availability of potential therapeutics on clinical trials that that will we will only increase so there's a there's a real opportunity.

Eric Dube: And that's just because of the methodology that's used. Oftentimes, these patients go undetected. And so we think, through increased awareness and the availability of potential therapeutics and clinical trials, that that will only increase. So there's a real opportunity in the U.S. and Europe there. We think that it fits very nicely into our portfolio. It's a rare disease that is oftentimes, Patients, if they are diagnosed early, are treated under the care of a pediatric geneticist and oftentimes across different specialties at tertiary care centers that focus on rare diseases.

In the U S and the Europe there.

We think that it fits very nicely into.

Patient folio, it's a rare disease that is often times.

These patients if they are diagnosed early or are treated under the care of of pediatric geneticists and oftentimes across different specialties of tertiary care centers that focus on rare disease.

And we.

Of our port through our KOL bond business.

Eric Dube: And we have, through our Colbaum business, a very strong team that has relationships and capabilities for navigating the diagnostic odyssey and helping clinicians treat and diagnose patients currently with bile acid disorders for Colbaum, but we think that it's gonna be very similar with the efforts around classical homosuspenaria. And we think that that serves as a nice example of how we might think about business development where we're going to continue to stay focused on rare diseases, and within rare diseases, we're going to be looking at that rare renal, hepatic, or metabolic condition where we will be able to leverage our late stage development and commercialization. In terms of the size of the deal, that certainly can evolve over time.

A very strong team that has relationships and capabilities of navigating the diagnostic Odyssey and helping clinic.

Clinicians treat and diagnose patients currently with bile acid.

Disorders for cobalt, but we think that it's going to be very similar.

Half of the with.

With the efforts around Costco home assistant.

Picked about knees is approved and we think that that serves as a nice example of how we might think about business development where.

We're going to continue to stay focused on rare disease and within rare disease therapeutically, we're going to be looking at that rare.

Yeah.

Renal hepatic or metabolic where we will be able to leverage our late stage development commercialization for.

Print.

In terms of the size of deal that certainly.

Can evolve over time, it's going to be something that we will continue to look at.

Greg Harrison: It's going to be something that we will continue to look at, but it's not something that I'd be able to provide more specifics on. Okay, that's helpful. Thanks. Your next question comes from Michelle Gilson with Canaccord. Your line is open.

But it's not something that I'd be able to provide.

For specifics at this point.

Okay. That's helpful. Thanks.

Thanks for it.

Your next question comes from Michelle Gilson with Canaccord. Your line is open.

Michelle Gilson: Hi, thanks for taking my question. I guess one clarifying question, so from your discussion around your EMA interaction. It sounds like the key difference between, I guess, what was discussed at the FDA and the EMA was really in this, I guess, interim look that you guys, I guess, second interim look that you guys may take in the first half of next year. Am I gathering this correctly, or is there some other, I guess, driver behind the EMA's willingness to allow you to file, like, I don't know, like greater reliance on proteinuria as a surrogate, or, you know, more comfort in the EGFR data that you showed them, or if it's a conditional, I guess, mechanism for approval that they have as an option?

Hi, Thanks for taking my question.

I think 1.

1 clarifying question.

On the discussion around your EMA interaction it sounds like.

The key difference.

Between I guess, what was discussed with the SBA and the EMA.

What's really in the <unk>.

The interim look day to day you Guy.

Yes.

Good morning, I guess second interim line that you guys May day.

The first half of next year.

Hey, my gathering this correctly or is there some other driver behind the willingness to allow you to file like gosh, I don't know like greater reliance on for generic.

Very good or.

More.

More comfort in the Egfr data that you showed them or if it's the conditional I guess mechanism for approval that the habit.

As an option.

Uh huh.

And then I do have a follow up okay.

Michelle Gilson: And then I do have a follow-up question. Bill, would you like me to... Certainly. I think it's difficult to compare the two agencies and their responses because there are different processes, and they go through, you know, independent review processes.

Bill would you like to take that.

Certainly.

I think it's difficult to compare the 2.

Agencies and their responses because there are different processes and they go through.

The independent review processes ultimately, they're performing the same function.

William E. Rote: Ultimately, they're performing the same function, but they did see the same data. They had the benefit of being aware of the strategy that we were taking or proposing to take with the agency and the supplementary EGFR data next year. And so, that was really the biggest difference. And at that point, it was, you know, around how do we work that into the review process and how might that be done with the mechanics of what's permissible, when can you put in additional data, and under what types of reviews that are allowable. That was really the key difference between them.

But they did see the same data they had the benefit of being aware of the strategy that we were taking are proposing to take.

With the agency in the supplementary Egfr data next year and so that was really the the.

The biggest difference and at that point it was.

Around how the how do we work that into the review process.

And how might that be done with the mechanics of what's.

Permissible when can you put in additional data in under 1 what types of reviews, that's allowable that was really.

The key difference there.

Michelle Gilson: Got it. And, you know, on TPT 058, I know there's been a lot of interest in, or pegbonotiny tonight. I just, you know, I'm wondering if you could clarify. You seem to be confident that either this dose or the next dose, or probably the effective dose or the go-forward dose. And, you know, is that really based on blinded data? Or are there some other factors?

Got it and you know on.

Until the T O 5 day.

I know there's been a lot of interest.

Pegged the not me, but the Tonight.

Can I ask.

I just.

I'm wondering if you could clarify you seem to be confident that this dose or the next dose are probably the effect of dose for dose and is.

Is that really based on blinded data or is there some other factors.

And then I guess would you expect I guess are you seeing anything in the safety of that would really prevent you from going higher if you wanted to to achieve the target product profile of that Youre looking for.

William E. Rote: And then I guess, would you expect, I guess, are you seeing anything in the safety that would really prevent you from going higher if you wanted to achieve the target product profile that you're looking for? Thanks, Michelle. Well, this is a blinded study, and we will have an interim look at the data at the completion of the current dose cohort. But we do look at the blinded study data in ag. At this point, there are no safety concerns that we're observing that look to be dose-limiting safety issues. Now, I say that from a position of not having full access to the data, so there's a qualifier there. But that's really not where our limits lie.

Thanks, Michele Bill why don't you take us.

Well this is a blinded study.

And we will have an interim look.

And look at the data at the completion of of the current dose cohort, but we do look at the blinded study data in aggregate at this point.

There are no safety concerns that we're observing that look to be dose limiting safety issues now I say that from the position of not having full access.

Looking data so there's a there's a qualifier on there, but that's really not.

There are limits line.

Michelle Gilson: We do believe that it's likely to be this dose or the next dose, but that's going to be determined by the data and when we're able to analyze all the biochemical data going forward. So, we should be able to give you at least a qualitative update later this year on how that looks going forward. Can I dig into that just a little bit more? You know, why?

We do believe that.

It's likely to be this dose or the next dose, but that's going to be determined by the data.

And when we're able to analyze all of the biochemical data going forward.

But we should be able to give you at least the qualitative uptake.

Later this year.

On on how that looks.

Going forward.

Can I kind of dig into that just a little bit more you know why I guess I am trying to figure out.

Eric Dube: I guess I'm trying to figure out, you know, if you could provide some perspective on why you're so confident that this dose or the next dose is probably going to be the go forward. Well, I would say, you know, it's, I wouldn't read it as confidence that it will be the right dose. I think it's, we're confident in the decision criteria that we're making. The design was, was well laid out.

You could provide some perspective on why you're so confident that this dose for the next dose.

There are probably going to go for it.

Well I would say.

I wouldn't read it as confidence that it will be the dose I think it's we're confident in the decision criteria that were making the design was was well laid out.

We now have the.

Eric Dube: We now have that latest dose cohort fully enrolled, and I think, you know, on a blinded basis, as Bill mentioned, we're seeing what we would expect and hope. So I think, you know, for us, it's how do we make sure we continue to execute, make the right decisions as we evaluate whether this is the right dose or not, or if we want to go higher. So I think that's really the way that I would characterize our thinking on this. And, you know, everything that we see is very consistent with a lot of the preclinical data and the hypothesis that drove the development.

That latest dose cohort.

The fully enrolled.

And I think on a blinded basis as Bill mentioned, we are seeing what we would expect and hope so I think for US. It's how do we make sure we continue to execute and make the right decision as we evaluate whether this is the right dose or if we want to go higher so I think that's really the.

On the way that I would characterize our thinking on this and everything that we see is very consistent with a lot of the preclinical.

Later on the hypothesis that drove the development program.

Okay. Thank you so much for taking my question Congrats on the question of them.

Michelle Gilson: Okay. Thank you so much for taking my question. Congratulations on the quarter. Your next question comes from Maurice Raycroft with Jefferies. Your line is open.

Your next question.

As for Maury Raycroft with Jefferies. Your line's open.

Maurice Thomas Raycroft: Hi everyone. Congratulations on the progress, and thanks for taking my question. I was wondering, for the IGAN phase 3, you're enrolling patients without washout for this study, and so they switched over to irvisartan or sparsantan from their optimized RAS inhibitor treatment. And so can you talk more about whether these patients have worsening UPCR when they are starting in phase 3, or are their EGFR stable? And then separately, what are your latest expectations on how irvisartan will perform and protect based on irvisartan outperforming in duplex? Maury, thanks so much for the questions. Noah, I'll pass this one over to you.

Hi, everyone. Congrats on the progress and thanks for taking my question.

I was wondering for the <unk> phase III youre enrolling patients without washout for the study and so they switched over to <unk>.

Kevin from their optimized Ras inhibitor treatment and so can you talk more about if these patients have worsening PCR when they are starting in the phase III or is their egfr is stable and then separately what are your latest expectations on how irbesartan will performance of attack.

Just on Irbesartan outperforming in duplex.

Good morning, Thanks, so much of the questions.

The pass this 1 over to you.

Yes.

The first.

Noah: Yeah, so I think the first question, Maury, if I heard you correctly, was about the washout in PROTECT. And so when these patients come in, they're in PROTECT required to be on a maximally tolerated dose of ACE or ARB treatment. And so the idea is that they switch to herbicortin. But we're currently blinded, so we don't know what happens to those patients. But the presumption is that there's potential with the lack of a washout and the maximally tolerated doses to have an optimal ACE or ARB on board, which then helps us to really show the difference between ERA inhibition on top of angiotensin.

Yes, So I think the first question Maury if I if I heard you correctly was about the washout in protect and so when these.

Patients come in.

There are in protect required to be on maximum tolerated dose of Easter our treatment and so the idea is the switch to irbesartan.

We're currently blinded so we don't know what happens to those patients, but the presumption is that theres the potential.

With the launch.

Lack of a washout and the maximum tolerated doses to has.

An optimal ASR on board, which could then help us.

2 really.

Show the difference between the E. R E inhibition on top of the angiotensin, whereas when you have non op.

Noah: Whereas when you have non-optimally or not maximally tolerated doses, there's a bit of a confounder there, right, which may also be clouding things a little bit. So I think that's the first point around the washout. What was the second?

Absolutely youre not maximize doses.

Net of a confounding of their REIT, which may also be the product things a little bit.

I think that's the first point around the the washout of what was the second can you just repeat the second question again.

Maurice Thomas Raycroft: Can you just repeat the second question again? Yeah, it's really nice to be here. Sorry. Go ahead. Yeah, go ahead.

Yes.

The second.

I'm sorry, Greg go ahead, Chris.

Okay.

Sorry, I was just going to add no. The question was around Irbesartan, but before we go to that I think the other aspect is just important as the inclusion exclusion criteria for protect which really does reflect that despite these patients being on Max tolerated ace or arb. They still are considered.

Christopher Cline: Sorry. Yeah, no, no, no. Sorry. I was just going to add, no, the question was around herbicartin. But before we go to that, I think the other aspect that's just important is the inclusion-exclusion criteria for PROTECT, which really do reflect that despite these patients being on max-tolerated ACE or ARB, they still are considered at risk. They're based on their UPC and, presumably, their EGFR. So these are patients that would not be considered well-controlled by treatment guidelines or by the nephrology community.

At risk based on their.

Yes the.

And presumably the Egfr. So these are patients that would not be considered <unk>.

Well controlled.

Bye bye treatment guidelines are for the the nephrology community. So we would fully expect that there would be continued decline in their renal function over time.

Are you piece of the background of what we understand about this disease. So sorry, no I thought that was an important point to mention and then we can go on to to Moore's question around what to expect on the Irbesartan.

Noah: So we would fully expect that there would be a continued decline in their renal function over time, just as a background to what we understand about this disease. So sorry, no, I thought that was an important point to mention. And then we can go on to Maurice's question about what to expect in herbicartin. So yeah, what's expected in herbicidin? So on that front, I would say, if you look at the literature across the studies, we're seeing in the teens up to 20 or 30% reduction in proteinuria with angiotensin blockade.

So yes, what's expected of Irbesartan. So on that front I would say if you look at the literature across the studies.

We're seeing in the teens up to 20 or 30% reduction in proteinuria with with orbit.

Angiotensin blockade.

Within our controlled setting the most recent analog.

It showed about a 5% difference and.

So I think we've got.

<unk>.

It's possible that we'll see something similar to 5% or somewhere between that and the other studies.

Noah: But within a controlled setting, the most recent analog, showed about a 5% difference. And so I think we've got, it's possible that we'll see something similar to 5% or somewhere between that and the other studies. But I think the important piece, again, is that we've got the maximally tolerated dose here, which is close to the optimized herbicidin dose. So we hope that, and we think there would be less of a difference there, and ultimately, you'll be able to really test the ERA on top of the angiotensin II hypothesis. That's the goal. I got it.

But I think the important piece again is is that we've got the maximally tolerated dose here, which is close to the the.

Optimize irbesartan dose. So we hope that we're thinking there would be less of the differences.

And ultimately you have.

Be able to really test the the.

Yeah Ray on top of the angiotensin 2 hypothesis ultimately that's the goal.

Got it that's helpful. Thanks for answering my questions.

Yeah, and I'll just add 1 more thing there are we've accounted for.

All of those scenarios in our power plants, and we have all of that covered.

The intercept wins.

Thank you.

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

Maurice Thomas Raycroft: That's helpful. Thanks for answering my questions. Yeah, and I'll add one more thing where we have accounted for all those scenarios in our powering plans. And we have all that, [inaudible] Thank you. Your next question comes from Laura Chico with Redbush Securities. Your line is open. Hey, good afternoon.

Hey, good afternoon, thanks for taking the questions I guess first.

For instance, we've gotten this on frequently from investors. So I just wanted to clarify.

It's around the disclosures you've provided so far around egfr from duplex and contrasting that versus what we've learned from others like your competitor <unk>. So I'm wondering what read through you see from their filing and I again towards your own with.

Laura Kathryn Chico: Thanks for taking the questions. I guess the first one; we've gotten this one frequently from investors. So I just wanted to clarify. It's around the disclosures you've provided so far around EGFR from Suplex and comparing that versus what we've learned from others like your competitor, Kaliditas. So I'm wondering what read through you see from their filing and IGAN towards your own with respect to, I guess, FDA's commitment to surrogate endpoints, but then also kind of around the EGFR disclosure strategy. And then I have a quick follow-up. Sure. Laura. Thanks so much for the question. I'll take this one.

First of all of them too.

Fda's commitment.

<unk> with surrogate endpoints, but then also kind of around the Egfr disclosure strategy and then I have a quick follow up.

Sure Laura Thanks, so much for the question I'll take this 1 I would say first that the the trial designs are different and so while other.

The risk that companies have disclosed egfr data from <unk> trials.

Those disclosure of those analyses are based on the completion of the treatment phase of the trial and so they are not ongoing blinded.

Studies in the same way that protect and duplex are in.

Eric Dube: I'd say, first of all, the trial designs are different, and so while other companies have disclosed eGFR data from IGAN trials, those disclosures and those analyses are based on the completion of the treatment phase of the trial. And so, you know, they are not ongoing, blinded studies in the same way that PROTECT and DUPLEX are. And so, there is just a slightly different way of managing the disclosure of data from an ongoing trial.

Other theres, just a slightly different way.

Of managing the disclosure of data from the ongoing trial and I think that that certainly has been informed by our continued engagement with regulatory regulators.

Now with regard to how.

Any potential read through I mean first.

So it's great to see the innovation and the positive results within the space that have just been lacking for decades.

Whether that's going to be incrementally confidence building for the FDA or not I'm not quite sure we certainly cannot speak for them.

Eric Dube: And I think that that, you know, certainly has been informed by our continued engagement with regulatory regulators. Now, with regard to any potential read-through, I mean, first and foremost, it's great to see the innovation and the positive results within the space that have just been lacking for decades. Whether that's gonna be incrementally confidence building for the FDA or not, I'm not quite sure. You know, we certainly cannot speak for them.

Reflecting the conversation.

And for me that we had with top of Nephrologist.

Certainly as incrementally.

Confidence building all of the data that's come out in this space.

That continued to show that.

Interventions that improve proteinuria are also improving egfr over time so.

<unk>, that's certainly what we're hearing from the Nephrology community I think we're optimistic and will continue to work on on the data package that will demonstrate that with sports center.

Eric Dube: You know, reflecting the conversations that we've had with top nephrologists, it certainly is incrementally building confidence in all of the data that's come out in this space that continue to show that interventions that improve proteinuria are also improving EGFR over time. So that's certainly what we're hearing from the nephrology community. I think we're optimistic, and we'll continue to work on a data package that will demonstrate that with sparse. Hopefully, that helps me to answer your question. It does, Eric.

With regulators hopefully that answer your question.

It does thank you very much and then I just have 1 follow up.

This is perhaps a broader higher level of strategic question on for certain but.

Would you still seek approval for <unk>.

As an accelerating filing cannot be completed then I guess kind of related to that.

Youre going to have a bit more understanding on where the answer agency stands.

Laura Kathryn Chico: Thank you very much. And then I just have one follow-up. And this is perhaps a broader, higher-level strategic question about Sparsanton.

Following the type of meeting.

Would you I guess look to pursue a similar strategy. If you had to and I again, if it didn't work out to have an accelerated filing.

Eric Dube: But, Would you still seek approval for FSGS if an accelerated filing cannot be completed? And, I guess, kind of related to that, you're going to have a bit more understanding of where the agency stands following your type A meeting. Would you, I guess, look to pursue a similar strategy if you had to in IGAN if it didn't work out to have an accelerated filing right away after the interim assessment?

Right of way after the interim assessment.

Yes. Thank you for the question I think.

When I said that we are undeterred.

Okay.

Whatever.

<unk>, we face I think that certainly extends to the scenario that you just laid out if for some reason we cannot gain alignment with the FDA and our type a meeting.

We're going to continue this trial out through the confirmatory endpoint and.

We will have the data on protect next month, we're still blinded, but once we see the interim we will be able to see how clear that accelerated pathway is or if we need to have similar types of conversations with them.

Eric Dube: Yeah, thank you for the question. I think, you know, when I said that we're undeterred by whatever challenges we face, I think that certainly extends to the scenario that you just laid out. If, for some reason, we cannot gain alignment with the FDA in our type A meeting, we're going to continue this trial out through the confirmatory endpoint. And, you know, we'll have data on PROTECT next month.

And the opportunity for accelerated approval, but we're committed to the space.

Continue to hear from the patient.

Patient community how important these programs are and we're not going to.

Net any of these aspects of the programs deter us.

Thank you so much Eric I appreciate it.

Eric Dube: We're still blinded, but once we see the interim, we'll be able to see how clear that accelerated pathway is or if we need to have similar types of conversations with them and the opportunity for accelerated approval. But we're committed to the space. You know, I continue to hear from the patient community how important these programs are. And, you know, we're not going to let any of these aspects of the programs deter us.

Alright, Thank you Laura.

I'm showing no further question at this time of I would now like.

Conference back to Chris Cline.

Great Thank drum on.

Thank you all for joining US today, we look forward to speaking with you again, when we have top line results from the interim Proteinuria assessment and protect study next month I Hope you all have a great rest of the week. Thank you.

Yes.

Ladies and gentlemen, this concludes today's call.

Conference. Thank you for your participation and have a wonderful day you may all disconnect.

Laura Kathryn Chico: Thank you so much, Eric. I appreciate it. All right. Thank you, Laura. I'm not asking any further questions at this time. I would now like to turn the conference back to Grace Cline.

[music].

Your line.

Okay.

[music].

The line.

Okay.

[music].

Christopher Cline: Great. Thank you, Jerome. And thank you all for joining us today. We look forward to speaking with you again when we have the top-line results from the Interim Protein Reassessment and PROTECT Study next month. I hope you all have a great rest of the week. Thank you. Ladies and gentlemen, this concludes today's conference. Thank you for your participation and have a wonderful day.

Yeah.

Yeah.

[music] line.

Operator: [inaudible] ??? ??? ??? ??? ???