Q3 2021 Travere Therapeutics Inc Earnings Call

[music].

Okay.

Operator: and Thank you for standing by, and welcome to Travere Therapeutics' third quarter 2021 financial results and corporate update call.

Good day, and thank you for standing by and welcome to for the year Therapeutics third quarter 2021 financial results and corporate update call. At this time all participants are in a listen only mode. Please be advised that this call is being recorded.

Operator: At this time, all participants are in a listen-only mode. Please be advised.

Operator: I apologize that this call is being recorded. If you require any further assistance, please press star zero. I would now like to hand the call over to our next caller.

You're acquiring further assistance. Please press star Zero I would now like to hand, the conference over to Chris Cline Senior Vice President of Investor Relations Corporate Communications. Please go ahead.

Operator: Star Zero. I would now like to hand the conference over to Chris Cline, Senior Vice President and Vestal Director.

Christopher Cline: Thank you, Justin. Good afternoon, and welcome to Travere Therapeutics' third quarter 2021 financial results and

Thank you Justin good afternoon, and welcome distributor Therapeutics third quarter, 2021 financial results and corporate update call. Thank.

Christopher Cline: Thank you all for joining us. Today's call will be led by our Chief Executive Officer, Dr. Eric Dube. Eric will be joined for the prepared remarks by Dr. Noah Rosenberg, our Chief Medical Officer, 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.

Thank you all for joining us today's call will be led by our Chief Executive Officer, Dr. Eric Today, Eric will be joined for the prepared remarks by Dr. Rosenberger, Chief Medical Officer, Peter Herma, Our Chief commercial officer, and our Chief Financial Officer, Laura Clague, Dr. Bill Rote Senior Vice President of research and development will join us for the Q&A session. Before we begin I would like to remind everyone that statements made.

Christopher Cline: Before we begin, I would like to remind everyone that statements major in 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.

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 by the statements.

Christopher Cline: Please see the forward-looking statement disclaimer in the company's press release issued earlier today, as well as the risk factors section in our Forms 10-Q and 10-K filed with the SEC.

Please see the forward looking statement disclaimer on the company's press release issued earlier today as well as the risk factors section in our forms 10-Q, and 10-K filed with the SEC. In addition, any forward looking statements represent our view only as of the date such statements are made October 28, 2021 trigger specifically disclaims any obligation to update such circumstances, they reflect future information events or circumstances with that.

Christopher Cline: In addition, any forward-looking statements represent our view only as of the date such statements are made, October 28, 2021, and Travere specifically disclaims any obligation to update such circumstances that reflect future information, events, or circumstances. With that, I now turn the call over to Eric. Thank you, Chris. And, by the way, happy birthday today. Good afternoon, everyone.

Let me now turn the call over to Eric Eric.

Thank you, Chris and by the way happy birthday today.

Good afternoon, everyone I am proud of the progress made across all facets of our business during the third quarter.

Eric Dube: I am proud of the progress made across all facets of our business during the third quarter. First, I am pleased to report that we achieved several significant milestones related to our goal of positioning sparsentin to ultimately become the new treatment standard for IJ nephropathy and FSGS, if approved. In August, we reported that our Pivotal Phase III PROTECT study of sparsentin in IJ nephropathy achieved its primary proteinuria endpoint with statistical significance at its pre-specified interminality.

First I am pleased to report that we achieved several significant milestones related to our goal of positioning <unk> to ultimately become the new treatment standard for Iga nephropathy and <unk>. If approved in August we reported that our pivotal phase III protect study of <unk> in Iga nephropathy.

<unk> achieved its primary proteinuria endpoint with statistical significance and its pre specified interim analysis.

Eric Dube: The result exceeded our expectations by demonstrating a greater than three-fold reduction in proteinuria from baseline compared to those patients receiving the active control herbicide. And at the time of the interim assessments, Sparcentin was generally well-tolerated and consistent with the observed safety profile to date. This is the first time a single non-immunosuppressive agent has demonstrated this magnitude of effect on proteinuria reduction in a large, well-controlled

The results exceeded our expectations by demonstrating a greater than three fold reduction in proteinuria from baseline compared to those patients receiving the active control irbesartan.

And at the time of the interim assessment <unk> was generally well tolerated and consistent with the observed safety profile to date.

This is the first time a single non immunosuppressive agent has demonstrated this magnitude of effect on proteinuria reduction and a large well controlled study.

Eric Dube: And we know from our engagement with the nephrology community that a treatment with these attributes is precisely what physicians are seeking to help prevent progression to end-stage kidney failure. I'm very pleased to report today that we've completed our pre-NDA interactions with the FDA for sparsentin in IJ nephropathy. Notably, the FDA agreed that the interim analysis from the PROTECT study supports submission of an application for accelerated approval under subpart A. Based upon the agency's feedback and alignment on our structure of the planned NDA, we expect to submit our application for accelerated approval in the U.S. in the first quarter of next year.

And we know from our engagement with the nephrology community that had treatment with these attributes is precisely what physicians are seeking to help prevent progression to end stage kidney disease.

Very pleased to report today that we've completed our pre NDA interactions with the FDA for sports Center in Iga nephropathy.

Notably the FDA agreed that the interim analysis from the protect study supports submission of an application.

Application for accelerated approval under Subpart H.

Based upon the agency's feedback and alignment on our structure of the planned NDA, we expect to submit our application for accelerated approval in the U S. In the first quarter of next year.

We also made meaningful progress on our <unk> program for FSD, yes. During the quarter. Most importantly, we gained alignment with the FDA on our plan to provide the agency with additional Egfr data from the ongoing duplex study in the first half of 2022, which enables us to continue on the accelerated approval pathway for <unk>.

Eric Dube: We also made meaningful progress on our Sparcentin program for FSGS during the quarter. Most importantly, we gained alignment with the FDA on our plan to provide the agency with additional EGFR data from the ongoing duplex study in the first half of 2022, which enables us to continue on the accelerated approval pathway for FSGS. If the additional EGFR data further strengthen the prediction of long-term benefit in the study, as we expect they should, we anticipate submitting an NDA for accelerated approval for FSGS in the middle of next year.

Yes.

If the additional Egfr data further strengthen the prediction of a long term benefit in this study.

As we expect they should we anticipate submitting an NDA for accelerated approval for <unk> in the middle of next year.

We are pleased that we now have a clear regulatory path to potential accelerated approval for <unk> and for both Iga nephropathy and <unk> in the U S and we look forward to achieving those submissions next year.

I'm also pleased to share that we have formalized our plan to pursue a combined.

<unk> nephropathy, and <unk> MAA submission for sports centered in Europe.

Eric Dube: We are pleased that we now have a clear regulatory path to potential accelerated approval for sparsentine for both IJ nephropathy and FSGS in the U.S., and we look forward to achieving those submissions next year. I'm also pleased to share that we have formalized our plan to pursue a combined IgA nephropathy and FSGS MAA submission for sparsantin in Europe. This strategic decision will allow us to pursue the most expedited path to making sparsantin available for both IgA nephropathy and FSGS in Europe, and we believe it will increase the probability of success in achieving optimal market access across regions.

This strategic decision will allow us to pursue the most expedited path to making <unk> available for both Iga nephropathy and <unk> in Europe, and we believe it will increase the probability of success for achieving optimal market access across regions.

Additionally, this option allows us to potentially request accelerated assessment for the review process.

We will continue our engagements with the EMA and expect the MAA application to be submitted mid next year. Once the planned additional egfr data from the duplex study can be incorporated if supportive.

Also as it relates to Europe, we were very pleased to recently enter into a joint collaboration and licensing agreement with <unk> for pharma for the commercialization of <unk> in Europe, Australia, and New Zealand.

Eric Dube: Additionally, this option allows us to potentially request an accelerated assessment for the review. We will continue our engagements with the EMA and expect the MAA application to be submitted mid-next year once the planned additional EGFR data from the duplex study can be incorporated, if supported. Also, as it relates to Europe, we were very pleased to recently enter into a joint collaboration and licensing agreement with V4Pharma for the commercialization of Sparsantan in Europe, Australia, and New Zealand.

This collaboration aligns the strength of two leaders in rare nephrology with a shared mission to making sports center, the new treatment standard for Iga nephropathy, and <unk>, if approved and it significantly increases our probability of success across all launches as it will allow us to have the dedicated.

Focus needed for successful launches in the substantial markets. The collaboration also recognizes the value of <unk> and can bring in Europe and strengthened our financial foundation with potential milestone payments totaling up to $845 million and royalties on sales in these regions of up to 40%.

We look forward to working closely with before they integrate <unk> into their portfolio and prepare for potential launches in Europe, Australia, and New Zealand beginning of 2023.

Eric Dube: This collaboration aligns the strengths of two leaders in rare nephrology with a shared mission to make Sparsentin the new treatment standard for IJ nephropathy and FSGS if approved. And it significantly increases our probability of success across all launches, as it will allow us to have the dedicated focus needed for successful launches in these substantial markets. The collaboration also recognizes the values Sparsantan can bring to Europe and strengthens our financial foundation, with potential milestone payments totaling up to $845 million and royalties on sales in these regions of up to 40%.

Beyond <unk>, we continue to be encouraged by the potential for our novel pegged about <unk> program in classical home assistant urea or <unk>.

We believe that it has the potential to become the first disease modifying therapy for the more than 7000 people in the U S and Europe, who are not adequately responding to current treatment options.

We remain on track for a preliminary assessment from the ongoing phase one two trial now named composed study.

Before year end and we look forward to establishing next steps for the program. If the data are encouraging as we expect.

Lastly, I'd like to highlight the performance of our commercial organization in the third quarter, our execution led to another quarter of year over year growth across all approved products. Despite the ongoing challenging environment created by the COVID-19 pandemic.

Eric Dube: We look forward to working closely with V4 as they integrate Sparcentin into their portfolio and prepare for potential launches in Europe, Australia, and New Zealand beginning in 2023. Beyond Sparcentin, we continue to be encouraged by the potential for our novel PEG-dibatinase program in classical homocystinuria, or HCU.

This performance underscores our confidence in the ability to successfully deliver sports center and picked up at least if approved let me now turn the call over to Noah for the clinical update.

Yeah.

Thank you Eric.

We remain very pleased with the progression of our pipeline of potential first in class therapies for people living with rare diseases.

The third quarter, we took meaningful steps towards advanced 6% in towards potential approvals.

Eric Dube: We believe that it has the potential to become the first disease-modifying therapy for the more than 7,000 people in the U.S. and Europe who are not adequately responding to current treatment. We remain on track for a preliminary assessment from the ongoing Phase 1-2 trial, now named the Composed Study, before year-end. And we look forward to establishing next steps for the program if the data are as encouraging as we expect. Lastly, I'd like to highlight the performance of our commercial organization in the third quarter.

Iga nephropathy.

Yes.

Most notable during the quarter, where the positive top line interim results from the ongoing pivotal phase III study of <unk>.

Hygienic property.

After 36 weeks of treatment patients receiving <unk> achieved a mean reduction in proteinuria from baseline.

49, 8%.

Impaired to a mean reduction in proteinuria from baseline of 15, 1%.

Eric Dube: Our execution led to another quarter of year-over-year growth across all approved products, despite the ongoing challenging environment created by the COVID-19 pandemic. This performance underscores our confidence in the ability to successfully deliver sparsentine and PEG-2BATnasive. Let me now turn the call over to Noah for the clinical update.

Irbesartan treated patients.

This result was clinically meaningful and statistically significant with a P value.

What's been 0.0001.

Preliminary egfr data available at the interim.

Interim analysis were consistent with our salary and indicative of a potentially clinically meaningful treatment effect after two years of treatment.

Noah Rosenberg: Thank you, Eric. I remain very pleased with the progression of our pipeline of potential first-in-class therapies for people living with rare diseases. In the third quarter, we took meaningful steps towards advancing Sparsantan towards potential approvals in both iGena Property and FHPA. Most notable during the quarter were the positive top-line interim results from the ongoing pivotal phase 3 tech study of spartan10 in myogenic prophecy. After 36 weeks of treatment, patients receiving SARTAN 10 achieved a mean reduction in protein area from baseline of 49.8% compared to a mean reduction in protein area from baseline of 15.1% for all SARTAN treated patients.

And from a safety perspective, we continue to be encouraged.

But the interim assessment.

It appeared to be generally well tolerated.

Consistent with previously observed safety profile.

These data build upon a robust data package.

Helped shape Sportscenter and safety profile.

Demonstrated the potential for clinically meaningful reductions.

Cross nearly 500 patients.

Iga nephropathy, and especially US Inc.

Including several patients that have been on therapy more than seven years and the open label extension of the phase two duet study.

This further supports our confidence in <unk>.

<unk> has the potential to meet the clear need for a new therapeutic option to meaningfully reduce proteinuria over to Paul widely used ace inhibitor and ARV treatments.

Noah Rosenberg: This result was clinically meaningful and statistically significant, with a p-value of less than 0.0001. Furthermore, preliminary EGFR data available at the time of the interim analysis were consistent with our powering and indicative of a potentially clinically meaningful treatment effect after two years of treatment. And from a safety perspective, we continue to be encouraged that the time of the interim assessment for assessment appeared to be generally well-tolerated, and it appeared consistent with the previously observed safety profile.

To do so while avoiding the long term safety challenges.

With immune suppression.

As Eric mentioned earlier, we recently completed our pre NDA interactions for Iga nephropathy, and we are very pleased with the successful outcome the <unk>.

<unk> agreement that the interim analysis for the protect study support submission of an application for accelerated approval under Subpart H.

Was clear.

With this feedback and alignment on the content and organization of our application.

We will be continuing our NDA preparations with the expectation of submitting in the first quarter of next year.

Noah Rosenberg: These data build upon a robust data package that has helped shape Sparsantan's safety profile and demonstrated the potential for clinically meaningful primary reductions across nearly 500 patients with IgNeprosopy and FSGI, including several patients that have been on therapy more than seven years in the open-label extension of the phase two duet study. This further supports our confidence that Scorcentine has the potential to meet the clear need for a new therapeutic option to meaningfully reduce proprionia over and above widely used ACE inhibitor and ARB treatments and to do so while avoiding the long-term safety challenges associated with immune suppression.

Our <unk> program also continued its forward momentum with the recent type of interaction, where we gained alignment with the FDA on our plan to provide the agency with additional Egfr data in the first half of next year to support a potential application for accelerated approval.

At the time of the plant Egfr data cut.

All patients remaining in the duplex study look completed at least one year of treatment.

And approximately 50% of patients will have completed two years of treatment.

We believe at this time point the data, we'll have sufficient maturity to straighten the prediction for long term benefit.

Noah Rosenberg: As Eric mentioned earlier, we recently completed our pre-NDA interactions for IGNephropathy, and we are very pleased with the successful outcome. The FDA's agreement that the interim analyses from the PROTECT study support submission of an application for accelerated approval under subpart 8 was clear. With this feedback and alignment on the content and organization of our application, we will be continuing our NDA preparations with the expectation of submitting it in the first quarter of next year.

If the data meet these expectations, we anticipate submitting an NDA mid next year.

Salary and approval of <unk> for US is just in the U S. In.

In parallel we'll be working on the combine Iga nephropathy and Atmos, yes.

Application for conditional marketing authorization.

<unk> in Europe with the expectation of a submission mid next year as well.

Both the protect and duplex studies.

Noah Rosenberg: Our FSGS program also continued its forward momentum with the recent Taipei interaction, where we gained alignment with the FDA on our plan to provide the agency with additional EGFR data in the first half of next year to support a potential application for accelerated approval. At the time of the planned EGFR data cut, all patients remaining in the duplex study will have completed at least one year of treatment, and approximately 50% of patients will have completed two years of treatment.

To advance.

And based upon progressed disease study.

Our well positioned.

Yes.

Inventory endpoints in 2023.

Lastly on the pipeline our optimism for the pace of Battens program remains high.

As it gets used to advance through the phase one to compose study.

Pose is a dose escalation study designed to assess the safety Tolerability pharmacokinetics, pharmacodynamics and clinical effects of <unk> in patients with HCM.

Patients in this study are being followed for up to 12 weeks in a blinded fashion and each cohort before entering an open label extension, we are anticipating a preliminary assessment from this study before year end.

Noah Rosenberg: We believe at this time point, the data will have sufficient maturity to strengthen the prediction for long-term benefit. If the data meet these expectations, we anticipate submitting an NDA mid-next year for accelerated approval of Spars Antenna for SSGS in the U.S.

And.

When we evaluate the preliminary data we will be examining a few factors.

Worse.

As you would expect with any early study of this nature is safety.

Noah Rosenberg: In parallel, we'll be working on the combined IgA nephropathy and FSGS MAA application for conditional marketing authorization of sparsantan in Europe, with the expectation of a submission mid-next year as well. Meanwhile, both the PROTECT and the DUPLEX studies continue to advance. And based upon the progress of these studies, are well-positioned to reach the playoffs in their confirmatory endpoints in 2023. Lastly, on the pipeline, our optimism for the Peg-to-Batneys program remains high, as it continues to advance through the Phase I-II Composed Study.

Are you looking for any signals of interest including immune response.

Next.

Is early evidence of efficacy.

Know that for those patients who are basics nonresponsive treating physicians typically toward getting patients below 100 microvolt of total homosapiens.

Pegged that needs to get patients below this level, we believe it could have the potential to become a clinically meaningful new treatment option.

When we provide our update later this year, we'll look to provide insight into some of these areas of focus.

Ill now turn the call over to Peter for the commercial update theater.

Noah Rosenberg: COMPOSE is a dose escalation study designed to assess the safety, powerability, pharmacokinetics, pharmacodynamics, and clinical effects of pentobatinase in patients with HCU. Patients in the study are being followed for up to 12 weeks in a blinded fashion in each cohort before entering an open-label extension, and we are anticipating a preliminary assessment from the study before year end. When we evaluate the preliminary data, we'll be examining a few factors. First, as you would expect with any early study of this nature, it's safe to say that we have. We'll be looking for any signals of interest, including immune response.

Thank you Bella and good afternoon.

We continue to be very pleased with our commercial organizations performance.

Specially in this environment virtual HCP interactions remain commonplace and we still see that fewer patients are visiting deficits compared to pre pandemic times.

In the third quarter, our execution, we sold 6% organic growth.

Product sales over the same period last year.

This was driven by underlying demand and strong patient compliance across the whole book.

Our cellular products, we continue to see new patients initiate treatment and to date, we have experienced limited impact from the generic version of the original formulation.

In the prior quarter.

Noah Rosenberg: Next, is early evidence of efficacy. We know that for those patients who are B6 non-responsive, treating physicians typically target getting patients below 100 micromoles of total homocysteine. If PEG-2 batonase can get patients below this level, we believe it could have the potential to become a clinically meaningful new treatment option.

Despite the limited impact plus four we do still anticipate an adverse impact comparable sales in the quarters ahead.

Our focus will remain on identifying new patients and <unk>.

Access to therapy and is providing the important services and supports many patients need to potentially be stone free.

The bile acid portfolio also continues to perform in line with our expectations.

Peter Heerma: When we provide our update later this year, we'll look to provide insight into some of these areas of focus. I'll now turn the call over to Peter for the commercial update.

As a result of the strong performance in the commercial portfolio over the last two quarters, we anticipate ending the year with low to mid single digit growth in net product sales over 2020.

Peter Heerma: Thank you, everyone, and good afternoon. We continue to be very pleased with our commercial organization's performance, especially in this environment where virtual ATP interactions remain commonplace, and we still see that fewer patients are visiting their physicians compared to pre-pandemic times. In the third quarter, our execution resulted in 6% organic growth in net product sales over the same period last year. This was driven by underlying demand and strong patient compliance across all products.

Given the COVID-19, pandemic and evolving dynamics.

B, a meaningful achievements and further bolster our confidence in our team's abilities going into a critical period of anticipated launches for sponsoring home.

We have plenty for launches of Spartan in both Iga nephropathy and <unk> in the U S.

We anticipate the first loss to now be in Iga nephropathy, and we have an incredibly exciting opportunity in front of us.

Peter Heerma: For our Stiola products, we continue to see new patients initiate treatment, and to date, we have experienced limited impact from the generic version of the original formulation that entered the market in the prior quarter. Despite the limited impact thus far, we do still anticipate an adverse impact on viola sales in the quarters ahead.

In the U S alone. We believe there are between 30 and 60000 patients living with Iga nephropathy.

Would be good candidates for spar center at launch.

Bruce.

And we believe the opportunity is likely to increase meaningfully overtime with greater awareness and diagnosis.

Peter Heerma: Our focus will remain on identifying new patients, ensuring access to therapy, and providing the important services and support that many patients need to potentially be stone free. The bile acid portfolio also continued to perform in line with our expectations. As a result of the strong performance of the commercial portfolio over the last two quarters, we anticipate ending the year with low to mid-single-digit growth in net product sales. Given the COVID-19 pandemic and the evolving dynamics, this would be a meaningful achievement and further bolster the confidence in our team's abilities going into a critical period of anticipated launches for Spartan.

We are well positioned to embark on our journey to reach these patients.

We will be growing our organization from a position of strength by scaling our infrastructure in net round geology.

Expand our coal plants and provide the services and support we know are critical for patients living with rare diseases.

And in market research studies with Nephrologist price due to protect data readouts, we lose that's far simpler hasnt emerging product profile.

Just to the top of the most desirable programs in development.

Given the strengths of the interim data from protect.

And the positive feedback we have received from the nephrology community since our topline announcement, we are calling for them.

Peter Heerma: We are planning for launches of SPAR Center in both IGA and FGS in the U.S. We anticipate the first launch to now be in IJN Frappuccino, and we have an incredibly exciting opportunity in front of us.

If approved we will be in a strong position.

Optimally established spar symptom is the new treatment standard for Iga nephropathy.

Peter Heerma: In the U.S. alone, we believe there are between 30,000 and 50,000 patients living with IgA nephropathy that would be good candidates for SportsSentiment at launch, if approved. And we believe that opportunity is likely to increase meaningfully over time with greater awareness and diagnosis. We are well-positioned to embark on our journey to reach these spaces. We will be growing our organization from a position of strength by scaling our proven infrastructure in rare nephrology to expand our call centers and provide the services and support we know are critical for patients living with rare diseases.

Overall, I have great confidence in our team's ability to <unk> syndrome to our multi multiyear track record of delivering life changing therapies to people living with rare diseases and I look forward to be sharing more about our progress as we continue to prepare the organization to political.

Angel upcoming launches.

Let me now turn the call over to Laura for the financial update.

Laura.

Thank you Peter.

The third quarter of 2021, we reported net product sales of $54 2 million from our commercial portfolio compared to 51.1.

Peter Heerma: And in market research studies with nephrologists, prior to the product data readouts, we learned that sparse symptom has an emerging product profile that rises to the top of the most desirable programs in development. Given the strength of the interim data from PROTECT and the positive feedback that we have received from the nephrology community since our top line announcement, we are confident that if approved, we will be in a strong position to ultimately establish Sparcentum as the new treatment standard for IGA nephropathy.

The same period in 2020.

We reported a GAAP net loss of $35 6 million for the third quarter of 2021.

After adjusting for noncash expenses and income tax we reported a non-GAAP net loss of seven 9% for the third quarter of 2021.

On a GAAP basis, R&D expenses were $48 4 million for the third.

Peter Heerma: Overall, I have great confidence in our team's ability to add Parcentum to our multi-year track record of delivering life-changing therapies to people living with rare diseases. And I look forward to sharing more about our progress as we continue to prepare the organization for the potential upcoming launch. I now turn the call over to Laura for the financial update.

Third quarter of 2021.

The increase compared to 2020 is largely attributable to increased patient enrollment in the ongoing studies as far.

As well as in dance advancement of the <unk> program and HD you.

On an adjusted basis R&D expenses were $45 2 million since third quarter of 2021.

Laura Clay: For the third quarter of 2021, we reported net product sales of $54.2 million from our commercial portfolio compared to $51.1 million for the same period in 2020. We reported a gap net loss of $35.6 million.

Relevant noncash expenses for the third quarter included $3 2 million stock based compensation and amortization.

On a GAAP basis, selling general and administrative expenses for the third quarter were $36 1 million.

Increase compared to 2020 is largely attributable to increased head count as well to the company's operations growth and professional fees.

Laura Clay: For the third quarter of 2021, after adjusting for non-cash expenses and income.

On an adjusted basis SG&A expenses for the third quarter with 25 points.

Laura Clay: We reported a non-GAP net loss of $7.9 million for the third quarter of 2021. On a gap basis, R&D expenses were $48.4 million for the third quarter of 2021. The increase compared to 2020 is largely attributable to an increase

Significant noncash adjustments for the quarter consisted of $10 6 million in stock based compensation and depreciation and amortization.

We ended the quarter in a strong financial position with $551 2 million in cash and cash equivalents.

The balance includes the $55 million upfront payment, we received as part of the joint collaboration licensing agreement with <unk> pharma. It was entered into during the quarter.

Laura Clay: Participation and Involvement in the Ongoing Studies of Sparsentine, as well as the Advancement of the PEG-Tubatinase Program

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

Laura Clay: Program in HCU.

Laura Clay: On an adjusted basis, R&D expenses were $45.2 million for the third quarter of 2021. Relevant non-cash expenses for the third quarter included $3.2 million in stock-based compensation and amortization.

As we look further out we anticipate significant investments throughout next year as we prepare for multiple potential product launches continue to support the ongoing studies of spar Simpson can advance are pegged to that program.

Taking into account the potential impact of generics, but.

Laura Clay: On a gap basis, selling general and administrative expenses for

But not including additional business development, we anticipate this cash balance to support our planned operations into 2023.

Laura Clay: The total expenses for the third quarter were $36.1 million.

Laura Clay: The increase compared to 2020 is large.

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

Laura Clay: Attributable to increased headcount as a result of the company's operational growth and professional services. On an adjusted basis, SG&A expenses for the third quarter were $25.5 million. Significant non-cash adjustments for the quarter consisted of $10.6 million in stock-based compensation and depreciation and amortization.

Thank you Laura I couldn't be more pleased with our organization's execution in the third quarter. We delivered impressive results from the pivotal phase III protect study.

We made considerable regulatory progress across our Spartan and programs.

Entered into a collaboration agreement with a global leader in nephrology to maximize the value of sports centered in Europe, Australia, and New Zealand and we continue to effectively deliver our approved products to patients in need.

Laura Clay: We ended the quarter in a strong financial position with $551.

With the regulatory pathways for Iga nephropathy in F. S. G. S. Now set we will be working in earnest to prepare three high quality NDA and MAA applications to be submitted next year and.

Laura Clay: $1.2 million in cash and cash equivalents. This balance includes...

Laura Clay: This concludes the $55 million upfront payment.

And we will continue our steps to prepare our organization to execute on successful launches of <unk> and if approved.

Laura Clay: received as part of the joint collaboration and licensing agreement with B4 Pharma that was entered into during the quarter.

Lastly, a few weeks ago, we announced the planned transition for Noah to an executive advisor role at the end of this year.

Laura Clay: For the balance of this year, we expect modest increases in our operating expenses. As we look further out...

I'd like to take this opportunity to thank him for all of his contributions and getting us to this strong position. We look forward to working closely with Noah to ensure a smooth transition in the coming months and his new role next year as we continue to advance our clinical studies and prepare our NDA and MAA applications.

Laura Clay: We anticipate significant investments throughout.

Laura Clay: Next year, as we prepare for multiple potential product launches, continue

Laura Clay: support the ongoing studies of Sparcentin and advance our PEG-Cubatinase program. Taken into account the potential impact of the generic formula, but not including additional business development, we anticipate this cash balance to support our planned operations into 2023. Now, I'll hand the call back over to Eric for his closing comments.

Thank you Noah.

Let me now turn the call over to Chris for Q&A Kris.

Great. Thank you Eric Jonathan can we go ahead and open up the lines for Q&A. Please.

Thank you as a reminder to ask a question you will need to press star one on your telephone to withdraw.

All your questions <unk>. Please standby, we compile the Q&A roster and again that is star one if you'd like to ask a question.

First question is going to come from Maury Raycroft from Jefferies. Your line is now open.

Hi, everyone. Congrats on the update and happy birthday, Chris.

Eric Dube: Thank you, Laura. I couldn't be more pleased with our organization's execution in the third quarter. We delivered impressive results from the Pivotal Phase 3 PROTECT study. We made considerable regulatory progress across our Spar Centen program, entered into a collaboration agreement with a global leader in nephrology to maximize the value of sparsentine in Europe, Australia, and New Zealand, and we continue to effectively deliver our approved products to patients in need. With the regulatory pathways for IJ nephropathy and FSGS now set, we will be working in earnest to prepare three high-quality NDA and MAA applications to be submitted next year. And we will continue our steps to prepare our organization to execute on successful launches of Sparcentin if approved.

I. My first question is if you can talk more about the Iga nephropathy pre NDA meeting and say if it was the more mature egfr data relative to <unk>. She asked that enable the FDA to concur that the interim analyses were adequate for submission and.

Can we assume that because of this iga nephropathy regulatory update that we can have more confidence at FSC has data will mature similarly.

Maury. Thanks, so much for the questions I'll turn that one over to bill.

Yeah. Thanks, Thanks for the question Maury.

Egfr picture for the protect study does represent a more mature data set that comes from a couple of things predominantly.

The enrollment dynamics were very different recall that the protect study began about six months behind the.

Duplex study so the work building the infrastructure was done on the duplex study in the protect study drafted in behind it so with linear.

Eric Dube: Lastly, a few weeks ago, we announced the planned transition for NOAA to an executive advisor role at the end of this year. I'd like to take this opportunity to thank him for all of his contributions in getting us to this strong position. We look forward to working closely with Noah to ensure a smooth transition in the coming months and in his new role next year as we continue to advance our clinical studies and prepare our NDA and MAA applications. Thank you, Noah. Let me now turn the call over to Chris for Q&A. Okay, Chris?

Linear enrollment dynamics, we had a much greater fraction.

The dataset that was out in the later time points and that was in Stark contrast to what we saw with the protect study to your other the other aspect of your question and confidence building for <unk> I think that when we look across the program for sentence three efficacy.

<unk> in two diseases and has performed very consistently across those studies. So when you allow the picture to mature.

Christopher Cline: Great, thank you, Eric. Justin, can we go ahead and open up the lines for Q&A?

<unk>, our expectation is that it's going to come in line.

Operator: Thank you. As a reminder, to ask a question, you'll need to press star 1 on your telephone. To withdraw your question, press the pound key.

And we will meet our expectations, we will have the data cut in the spring and that will that.

That will give us that answer.

Great.

Maybe one follow up if you could just remind what your expectations are for the review period.

Operator: Please stand by. We'll compile the Q&A roster. And again, that is Star 1 if you'd like to ask a question. And our first question is going to come from Maurice Raycroft from Jeffries. The line is now open. Hi everyone, congrats on the update and happy birthday, Chris.

For for both programs for <unk> and Iga nephropathy.

So for the protect study we will be requesting priority review. So if we submit in the first quarter than we if we are granted priority review, which we certainly believe this disease and this drug warranted with this dataset.

Maurice Thomas Raycroft: My first question is, if you can talk more about the IgA nephropathy pre-NDA meeting and say if it was the more mature EGFR data relative...

That would mean, we'd have an answer from the agency.

The day before the end of 'twenty two.

Maurice Thomas Raycroft: FDA to concur that the interim analyses were adequate for submission, and can we assume that, because of this IgA nephropathy regulatory update, we

For <unk>, we expect to submit that in the middle of the year next year following <unk>.

Interaction with the FDA on Egfr cut should those data filing that would be a mid year.

Maurice Thomas Raycroft: We can have more confidence that FSGS data will mature similarly.

22 filings so priority would put that in the first half of 'twenty.

William E. Rote: Maury, thanks so much for the questions. I'll turn that one over to Bill.

Sorry.

If it's standard review it would be early in the second half.

William E. Rote: Yeah, thanks. Thanks for the question, Maury. The EGFR picture for the PROTECT study does represent a more mature data set, and that comes from a couple of things. predominantly, the enrollment dynamics were very different. Recall that the PROTECT study began about six months behind the duplex study. So the work building the infrastructure was done on a duplex study, and the PROTECT study was drafted in behind it. So with a linear-much more linear enrollment dynamics, we had a much greater fraction of the data set that was out in the later time points.

Great. Okay, Congrats again and thanks for taking my questions.

Sure thing Thank you ward.

And thank you and our next question comes from Greg Harrison from Bank of America. Your line is now open.

Good afternoon, guys. Thanks for taking our questions.

First one is on pegged to that nice.

What is the extent of the data that we could expect to see in the in the coming readout.

And what would you consider to be clinically meaningful there.

And then assuming it is what would be the next steps for this program.

If the data are supportive of moving forward.

Yeah. So thanks, so much Greg for the questions I'll take the first one on what we can expect and then.

William E. Rote: And that was in stark contrast to what we saw with the PROTECT study. To your other question and competence building for FSGS, I think that when we look across the program, Sparsantan has been in three efficacy studies in two diseases and has performed very consistently across those studies. So when you allow the picture to mature in duplex, our expectation is that it's going to come in line and will meet our expectations. We'll have the data cut in the spring, and that will-

I'll ask bill to share a little bit more around the next steps. So as <unk> mentioned you were really looking at a couple of key areas with this analysis from the composed study first and foremost. This is the first study in humans. So we want to have a particular eye on safety.

The second aspect is to really understand the dose response in this trial given that we are studying different dose cohorts.

And then the third and I think particularly around your question of what would be considered clinically meaningful is to assess whether patients are able to get below 100 micro molar for total home assistant urea and whether they are able to stay below those levels that is considered.

The treatment goal in the guidelines and by clinicians and patients.

William E. Rote: That will give us that answer.

With home assistant urea, so we're going to be particularly looking at that threshold.

William E. Rote: Great. And maybe one follow-up, if you could just remind me what your expectations are for the review period for both programs, for FFA.

And we'll obviously continue to assess that but those are the major areas of focus as we go into that analysis.

William E. Rote: Both programs for FSGS and Hygiene and Property.

And I'll turn it over to Bill to talk about next steps.

William E. Rote: So, for the PROTECT study, we will be requesting priority review. So, if we submit in the first quarter, then we, if we are granted priority review, which we certainly believe this disease and this drug warrant it with this data set, that would mean we'd have an answer from the agency, a PDUCA date before the end of 22. For FSGS, we expect to submit that in the middle of the year, next year, following interaction with the FDA on EGFR cut.

The first step will be to analyze the data from the Internet interim analysis, and we expect to share that at least to some degree the <unk>.

Next immediate step is really to use that data.

Dataset and engage with regulators and that'll be the results from the interim analysis of the proposed study as well as the.

Current data from the natural history study.

We will then take their input into our own feasibility analyses and work toward developing a plan for the next clinical study in parallel to that we'll be working on manufacturing scale up and process development.

William E. Rote: And should those data support filing, that would be a mid-year 22 filing. So priority would put that in the first half of 2020. 3, and if it's standard review, it would be early in the second half of 2020. Great, okay, congrats again and thanks for taking my questions.

The goal is ultimately going to be to move downstream from the compose study into a pivotal study.

And that next phase of development, and we will be able to share more about that once we had those engagements with the agents.

Greg Harrison: And thank you. And our next question comes from Greg Harrison from Bank of America. Your line is now open. Good afternoon, guys. Thanks for taking our questions.

Okay. That's helpful and then if I can sneak in one more.

As far as the.

Again program.

Would you expect that there would be an AD com needed there.

Bill.

Greg Harrison: The first one is on PEG-to-BAT NACE. What is the extent of the data that we could expect to see in the coming readout, and what would you consider to be clinically meaningful there? And then, assuming it is, what would be the next steps for this program if the data are supportive of moving forward?

One of the questions. We asked in our pre NDA interactions was their perspective on whether or not we would have.

Have an ad com.

The agency said that based on the data they've seen thus far they don't anticipate calling for an advisory committee.

We're not surprised with that.

Given the data from the interim analysis, and we see that as a positive.

Eric Dube: Yeah, so thanks so much, Craig, for the questions. I'll take the first one on what we can expect, and then I'll ask Bill to share a little bit more about the next steps. So, as Noah mentioned, we're really looking at a couple of key areas with this analysis from the COMPOSE study. First and foremost, this is the first study in humans, so we wanna have a particular eye on safety. The second aspect is to really understand the dose response in this trial, given that we are studying different dose cohorts.

These things can change and we will be prepared should and Ed can be called but at this point, we don't expect to have one.

Great very helpful. Thanks, again, and congrats again on all the progress.

Thank you Brian.

And thank you.

And our next question comes from Joseph Schwartz from SBB Leerink. Your line is now open.

Hi, Thanks, very much I was wondering if you'll be reporting any more data to investors at the time that you perform your next interim analysis of the duplex study in the first half of 'twenty two or.

Eric Dube: And then the third, and I think particularly around your question of what would be considered clinically meaningful, is to assess whether patients are able to get below 100 micromolars for total homocysteineuria and whether they're able to stay below those levels. That is considered the treatment goal in the guidelines and by clinicians and patients with homocystinuria.

Well all of the information just be for the FDA and likewise, when we hear whether the FDA has any feedback for the company on your plan to file as occurred when you performed your first interim analysis.

Joe Thanks, so much for the questions. So as part of our interactions and plans for that additional Egfr cut we're going to be working with the FDA on any disclosure plans I would say, it's probably safe to assume that that we would not be providing any additional data given that it's the trials on.

Eric Dube: And so, you know, we're gonna be particularly looking at that threshold. And, you know, we'll obviously continue to assess that, but those are the major areas of focus as we go into that analysis, and I'll turn it over to Bill to talk about next steps. Thanks, Eric.

Going and we continue to be very focused on maintaining that blind and the trial integrity.

Really what we're going to be focusing on in large part is to communicate following the meeting once we receive minutes or once we have submitted or accepted.

William E. Rote: Yeah, the first step will be to analyze the data from the interim analysis, and we expect to share that at least to some degree. The next immediate step is really to use that data set and engage with regulators. And that will be the results from the interim analysis of the composed study, as well as the current data from the natural history study. We'll then take their input and do our own feasibility analyses and work toward developing a plan for the next clinical study.

By FDA.

The NDA and so that really is going to be our focus as we look at those additional data, but as I've mentioned, we're going to be working with FDA to see what they are comfortable with us disclosing at that point.

Great. Thanks for the color.

And then how would you rate the awareness and appreciation of proteinuria lowering as an important treatment goal in the community physicians, who see the most <unk> and Iga nephropathy patients how ready is the market to adopt the proteinuria lowering agent like Spartan Pan and how much education do you still need to.

William E. Rote: In parallel to that, we'll be working on manufacturing scale-up and process development. The goal is ultimately going to be to move downstream from the composed study into a pivotal study in that next phase of development, and we'll be able to share more about that once we've had those engagements with the agency.

Undertake in order to encourage strong uptake in the real world.

Yeah. Thanks for that question.

Both Peter and no answer that given that Peter's team is working very much on a lot of the market research with the broader nephrology community knowing his team with some of the top nephrologist and they can provide a bit of feedback on what they are hearing.

Greg Harrison: Great, that's helpful. And then I could sneak in one more.

Greg Harrison: As far as the IGAN program.

Greg Harrison: Program. Would you expect that there would be an adcom needed there?

Peter you want to start.

Yes, Thanks, Eric and thank you Joe for the question well what have we learned from the market research as well as the thought leaders that we are speaking with Julia.

William E. Rote: One of the questions we asked in our pre-NDA interactions was their perspective on whether or not we would have an ADDCOM. The agency said that based on the data they've seen thus far, they don't anticipate calling for an advisory committee. We're not surprised by that, given the data from the interim analysis, and we see that as a positive. That said, these things can change, and we'll be prepared should an ADDCOM be called, but at this point, we don't expect to have it.

The markets that we sold to treatment initiation and monitor monitoring of patients how well they are doing.

We think it makes sense because both of you is also the strongest predictor of progression of disease.

So I think there is a well established.

Understanding of proteinuria and its relation to progression of disease in particular patient from higher risk towards dialysis no I don't know if you want to build upon that.

Greg Harrison: Great, very helpful. Thanks again and congrats again on all the progress.

Yes.

Joseph Patrick Schwartz: Thank you. And our next question comes from Joseph Schwartz.

Thanks.

I think that's right Peter.

I think physicians neurologists, specifically are acutely aware of the toxic effects of.

Joseph Patrick Schwartz: and Joseph Schwartz from SVB Larynx. The line is now open.

Joseph Patrick Schwartz: Hi, thanks very much. I was wondering if you will be reporting any more data to investors at the time that you perform your next interim analysis of the duplex study in the first half of 2022, or will all of the information just be for the FDA? And likewise, will we hear whether the FDA has any feedback for the company on your plan to file as a

Proteinuria.

We speak to that AD words, all the time.

They are aware of the concern that proteinuria will drive worsening outcomes and ultimately patients dialysis the need for renal replacement therapy.

I think where the education comes in is now that we have additional therapy and a potential therapy, it's around targets educating around those targets, where they can realistically go because it really had such limited options until now specifically at <unk> for instance.

Joseph Patrick Schwartz: as occurred when you performed your first interim analysis. Joe, thanks so much for the questions.

Eric Dube: So as part of our interactions and plans for that additional EGFR cut, we're going to be working with the FDA on any disclosure plans. I would say it's probably safe to assume that we would not be providing any additional data given that the trial is ongoing and we continue to be very focused on maintaining that blind and the trial integrity. Really, what we're going to be focusing on in large part is communication following the meeting once we receive the minutes or once we have submitted or accepted the NDA by FDA.

Your choices are very limited aces and arbs, we know often fail and immune suppressants are very limited in that they can create concerns around.

Youre short term treatments and they often don't work, so I think awareness around <unk> and the mechanism how it works.

The safety data set is really important because we get the message out there that you know realistically, what's the truck like sports Center, and there's a better chance of them achieving some of these targets that have been set up by the guidelines. So I think that that's certainly an area that we're focused on.

Eric Dube: And so that really is going to be our focus as we look at those additional data. But as I've mentioned, we're going to be working with FDA to see what they are comfortable with us disclosing at that point.

Sounds good thanks for taking my questions and best wishes to Noah.

Thanks, Hey, Keith.

Eric Dube: Great, thanks for the color. And then, how would you rate the awareness and appreciation of protein-area lowering as an important?

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

Joseph Patrick Schwartz: Treatment Goal in the community of physicians who see them the most.

Hi, Thank you for taking my question.

Joseph Patrick Schwartz: F.S.G.S. and I.G.N.O. property patients

I guess I'm wondering if you could provide a little bit more color around your pre NDA meeting.

Eric Dube: How ready is the market to adopt a proteinuria-lowering agent like SPARS and PAN, and how much education do you still need to undertake in order to encourage strong uptake in the real world? Yeah, thanks for that question. I'll have both Peter and Noah answer that, given that Peter's team is working very much on a lot of the market research with a broader nephrology community. Noah and his team are working with some of the top nephrologists, and they can provide a bit of feedback on what they are hearing. Peter, do you want to start?

What the FDA was most focused on and I guess more specifically, what Egfr analyses were done and presented to the agency.

Yeah.

Again.

I know we've discussed in the past that there are different ways that you can evaluate changes in egfr.

So and.

Also I think I heard you earlier alluded to priority.

Review timelines for.

I was just curious if that was discussed during our pre NDA meeting.

Thanks, Michele Bill would you like to take those questions.

Peter Heerma: Yeah, thanks Eric and thanks Jo for the question. Well, what we learned from the market research as well as the thought leaders that we are speaking with is that proteinuria is often the market that results in treatment initiation and monitoring of patients, and how well they're doing, which I think makes sense because proteinuria is also the strongest predictor of progression. So I think there is a well-established understanding of proteinuria and its relation to progression of disease, in particular patients at higher risk for dialysis. No, I don't know if you want to build upon that. Yeah, yeah.

Sure I think I I think I've got them all.

Now as far as what was presented.

To the agency for the pre NDA interactions the briefing book presented a comprehensive summary.

The interim analysis. So it was proteinuria measured multiple different ways or expressed different ways Egfr versus time split by groups and a summary level both observed in the memorial <unk>, which is the primary analysis endpoint and.

And additionally.

Some review of safety and adverse.

Events, so that was.

The analyses were presented.

Noah Rosenberg: Yeah. Yeah. I think that's right, Peter.

Your question around priority review.

Noah Rosenberg: I think physicians, nephrologists specifically, are acutely aware of the toxic effects of proteinuria. You know, we speak to them at AdWords all the time, and they're aware of the concern that proteinuria will drive worsening outcomes and ultimately hasten dialysis and the need for immunoreplacement therapy. I think where the education comes in is now that we have additional therapy and potential therapies around targets, educating around those targets, where they can realistically go, because they've really had such limited options until now.

Certainly believe that this is it.

The deal case for priority review.

But that's not something that gets granted at this stage of the game, we intend to request it.

And we see this as an ideal case for it but we won't know the answer to that question until after we've submitted the NDA in the first quarter.

Okay and then.

One if I can unpack that.

Well.

Hmm.

You're evaluating different dose levels now and you've indicated that you may evaluate another dose level.

Noah Rosenberg: Specifically, in IgAN, for instance, your choices are very limited. ACEs and ARBs, as we know, often fail. And immunosuppressants are very limited in that they can create those concerns around safety. They're short-term treatments, and they often don't work.

I'm just curious.

If you expect that you'll evaluate different dose intervals at another dose level.

Yes.

I guess I.

Hi, guys.

Bill.

Yeah.

We have said that within this study we're looking both at dose regimen and dose levels.

Noah Rosenberg: So I think awareness around Sporcentin, the mechanism, how it works, and the safety data set is really important that we get the message out there that, realistically, with a drug like Sporcentin, there's a better chance of them achieving some of these targets that have been set out by the guidelines. So I think that that's certainly an area that we're focused on. Sounds good. Thanks for taking my questions and best wishes to NOAA. Thank you. And our next question comes from Michelle Gilson.

We will make the decision on what we're going to do with the next cohort when we see the data in December so it could be either of those or it could be state.

Staying at the same level of dose and increasing the amount of experience at the at the current level.

So it's going to be a data driven decision once were on blinding at interim.

Later this year.

Oh, Okay, if I could just.

Is there any I guess.

Are there any issues with going up in volumes here I know it just stopped.

Michelle Gilson: Gilson from Canaccord Genuity. Your line is now open.

Michelle Gilson: Hi, thank you for taking my question. I guess I was wondering if you could provide a little bit more color around your pre-NDA meeting and what the FDA was most focused on. And I guess, more specifically, what EGFR analyses were done and presented to the agency for IGAN. And I know we've discussed in the past that there are different ways that you can evaluate changes in the EGFR. So, and, you know. Also, I think that I heard you earlier allude to priority review timelines for IGAN, and I was just curious if that was discussed during your pre-NDA meeting.

You go.

If you do evaluate a higher dose.

So the there.

There are limits to how much is tolerable on an individual's sub Q injection.

You increase in dose depending on the solubility of the agents that youre working with.

There can be limits there.

Becomes balance.

Between patient need and what's patient, what's acceptable with patients, but one of the easy ways to deal with that.

Flip the injection.

You are going to higher doses are higher volume.

Multiple sub two injections.

Tends to ameliorate the issue.

Okay. Thank you guys. So much for taking my questions.

William E. Rote: Thanks, Michelle. Bill, would you like to take those questions?

Certain shop.

And thank you.

And our next question comes from Lisa Baker from Evercore ISI.

William E. Rote: Sure, I think I've got them all jotted down. As far as what was presented to the agency for the pre-MDA interactions, the briefing book presented a comprehensive summary of the interim analysis. So, it was proteinuria measured multiple different ways or expressed in different ways, EGFR versus time split by groups at a summary level, both observed, and then the MMRM, which is the primary analysis endpoint, and additionally, a summary view of safety and adverse events.

Your line is now open.

Hi.

I guess congratulations are in order for both Chris and Noah So congratulations to you both and.

I think feels like a lot of questions on HCM with getting a bunch of work on it.

And I think the main question I'm getting is just like how much information investors aren't going to get.

When you do kind of preview some data. So can you maybe just elaborate to so expectations.

Our set appropriate lists of what kind of information you're going to get and how you know how much you can kind of like you know communicate you know what youre seeing in <unk>.

William E. Rote: So, that was how the analyses were presented. Your question about priority review, we certainly believe that this is an ideal case for priority review, but that's not something that gets granted at this stage of the game. We intend to request it, and we see this as an ideal case for it, but we won't know the answer to that question until after we've submitted the MDA in the first quarter.

<unk> of response in patients.

Sure I'll take that one Lisa and our focus again is on those three areas of safety dose response and magnitude of effect on total homocysteine. There of course, our other measures of efficacy that we're looking at for example in defining as a biomarker that is often assess.

Within <unk>, so we're going to be looking at those aspects as well.

Michelle Gilson: Okay, and then, you know, one, if I can unpack that as well, you know, you're evaluating different dose levels now, and you've been

I'd say the expectation.

Is that we want to make sure that we provide clarity on each of those questions. Once we have the data readout.

William E. Rote: You may evaluate another dose level, and I'm just curious if it's because you expect that you'll evaluate different dose intervals at another dose level or if it's just, I guess, higher doses.

We've not yet committed to weather.

Data, we're going to be disclosing at that time, given that one is the competitive space and we want to make sure that we're not providing so much so as to lose the lead that we have in this space, but we also want to make sure that we really have a good understanding of what that dose.

Michelle Gilson: Yeah, we have said that within this study, we're looking both at dose regimen and dose levels. We will make the decision on what we're going to do with the next cohort when we see the data in December. So it could be either of those, or it could be staying at the same level of dose and increasing the amount of experience at the current level. So it's going to be a data-driven decision once we're unblinding at interim later this year.

That dose and dose regimen is and whether we believe that we have the right dose, we certainly wouldn't want to.

Communicate efficacy if we believe that there is something more that we could be pursuing so that's a little bit of how we're thinking about it.

We said that at a minimum will provide a qualitative update on each of those three questions, but we very well could be in a position to provide.

More specific data.

As we move forward.

And then the.

Michelle Gilson: Okay, if I could just follow up, are there any I guess issues with going up in volume here? I know it's a sub-two dose, but you know, if you do evaluate a higher dose.

Any kind of additional color on timing.

Well, we're on track to be able to provide that update.

Sometime later this year, but.

To be able to narrow that down even further.

We're just not at that point to do so, but we're very near.

Michelle Gilson: So, there are limits to how much is tolerable on an individual sub-Q injection. As you increase in dose, depending on the solubility of the agent that you're working with, there can be limits there. It becomes a balance between patient need and what's patient, what's acceptable with patients. But one of the easy ways to deal with that is to split the injection if you are going to higher doses or higher volume into multiple sub-Q injections. And that tends to ameliorate the issue. Thank you very much.

Okay and then just finally on the on the same program.

Kind of what I look at it I think it could be at least as big of an opportunity as far as Santana in terms of its value.

Because it has a pretty long like revenue tail, it actually could be pretty valuable.

As a relative.

Relative to the percent in more valuable actually can you maybe comment on how youre thinking about.

Kind of the size of the opportunity and provide some benchmark.

Well, we certainly are excited about the opportunity given that there is a high unmet need here.

The addressable population if we start there is 7000 patients currently across the U S and Europe, but I think we recognize that there are a few areas that really can be approved which we believe is typically the case within rare disease.

Michelle Gilson: Thank you guys so much for taking my questions. (inaudible)

One is that these patients are oftentimes on diagnosed.

Liisa Ann Bayko: And our next question comes from Liisa Bayko from Evercore ISI.

Despite newborn screening many of these patients still are not.

Liisa Ann Bayko: Hi, I guess congratulations are in order for both Chris and Noah. So congratulations to you both.

Diagnosed early enough.

And go into adulthood before being effectively diagnosed.

And while there are other therapies like high dose vitamin B six.

Liisa Ann Bayko: And I've been fielding a lot of questions on HCU, and we've been doing a lot of work on it. And I think the main question I'm getting is just like how much information investors are going to get when you kind of preview some data. So can you maybe just elaborate on what our expectations are appropriately set about what kind of information you're going to get and how, you know, how much you can kind of like, you know, communicate, you know, what you're seeing in terms of response in patients.

The literature states that propel.

Proportion of up to 50% that are responsive when we talk to experts in this area.

They are very clear that that.

That is a very high estimate of six responsiveness. So we think that there's still opportunity there to better understand where the unmet need is and who is above the key thresholds. So that's going to be a big part of what we're doing in parallel to clinical development.

At this time and I'd say that it's a shift in enzyme replacement therapy. So we'll continue to assess what the benchmarks are for pricing and what value. We bring there, but we do believe that this is a significant opportunity for us and we are.

Eric Dube: Sure, I'll take that one, Liisa. And, you know, our focus, again, is on those three areas of safety, dose response, and magnitude of effect on total homocysteine. But there, of course, are other measures of efficacy that we're looking at. For example, methionine is a biomarker that is often assessed within HCU.

We are currently first in development and we are really focused on ensuring that lead position.

Thank you very much thanks.

Thanks Lisa.

Thank you.

Our next question comes from Carter Gould from Barclays. Your line is now open.

This is Justin on for Carter, Thanks for taking the question and congrats on all the progress this quarter.

Eric Dube: So we're going to be looking at those aspects as well. I'd say the expectation is that, you know, we want to make sure that we provide clarity on each of those questions once we have the data readout. But we've not yet committed to whether or not we're going to be disclosing how much data at that time, given that, you know, one, it's a competitive space, and we want to make sure that we're not providing so much so as to lose the lead that we have in this space.

Just one quick wrap up one for us on <unk> understanding that.

I want to see.

So the two revealing on what data you expect to show on the readout, but Eric you mentioned earlier that duration of response is going to be sort of a key criteria and you're moving forward decisions I'm. Just wondering if you can tell us how much duration data we should expect in the first readout, how much that's going to impact.

Your next steps with the program.

Okay.

If youre going to be waiting on any more duration data going forward before you move ahead with the program.

Eric Dube: But we also want to make sure that we really have a good understanding of what that dose, you know, that dose and dose regimen is, and, you know, whether we believe that we have the right dose. We certainly wouldn't want to communicate efficacy if we believe that there's something else, you know, more that we could be pursuing. So that's a little bit of how we're thinking about it. We said that, at a minimum, we'll provide a qualitative update on each of those three questions, but we very well could be in a position to provide, you know, more specific data as we move forward.

Sure I'll ask bill to talk a little bit about what we're going to be looking at and what the trial design will allow in terms of.

Follow up.

Yes, so from a from a duration perspective, we'll have double blind data.

Everybody in the interim through.

Through 12 weeks, but then those patients go on to continue is an open label extension. So for many of the patients will have significantly longer.

Longer windows 10 for that so.

As is often true in metabolic disease.

Biologic biochemical endpoints there is a degree of variability.

That is certainly aided when you look with a longer window of ascertainment. So the trial design is very strong for that.

Liisa Ann Bayko: And any kind of additional color on timing?

Eric Dube: Well, we're on track to be able to provide that update sometime later this year, but to be able to narrow that down even further, I would say we're just not at that point to do so. But we're very near.

Awesome. Thank you very much.

Thanks, Jess and thank you.

And if you have a question that is star one again, if you have a question that is star one and our next question comes from Tim Lugo from William Blair. Your line is now open.

Liisa Ann Bayko: Okay, and then just finally, on the same program, you know, kind of when I look at it, I think it could be at least as big of an opportunity as Bar-Santan, and in terms of its value, because it has a pretty long, like, revenue tail, it actually could be pretty valuable as a, you know, relative to Bar-Santan, more valuable, actually. Can you maybe comment on how you're thinking about kind of the size of the opportunity and provide some benchmarks? Well, we certainly are excited about the

Hey, guys. This is work on them.

Second question.

I was just wondering Eric if you could maybe.

A bit more color on the process behind choosing to pay for the partner in Europe.

Their infrastructure is why that makes sense.

Pardon.

<unk> always thought that then.

Well.

On the <unk> application.

Disgusting.

Yes.

Submitting the combined application.

Yes.

Eric Dube: Well, we certainly are excited about the opportunity, given that there is a high unmet need here. The addressable population, if we start there, is 7,000 patients currently across the U.S. and Europe. But I think we recognize that there are a few areas that really can be improved, which we believe, you know, is typically the case within rare diseases. One is that these patients are oftentimes undiagnosed. Despite newborn screening, many of these patients are still not diagnosed early enough and go into adulthood before being effectively diagnosed.

The payback on that.

Great.

Okay sure. So lachlan. Thanks, so much for the questions I'll take the first one on really how are how we're thinking evolved to selected <unk> as our partner.

And then I'll ask bill to talk a little bit more about our engagements with the EMA.

So as we set out to assess.

The <unk>.

<unk> partnering in Europe with <unk>.

Really it led us to think about who has an established presence within nephrology and when we think about that it's not just having the relationships with Nephrologist, which V. For clearly has they have relationships not just with the majority of nephrology practices within Europe, but also with some of the top.

Eric Dube: And you know, while there are other therapies like high-dose vitamin B6. The literature states that there is a proportion of up to 50% that are responsive. However, when we talk to experts in this area, they are very clear that that is a very high estimate of B6 responsiveness.

Kols. They also have experience in working with regulators and with HCA bodies, not just nationally, but also regionally and in some countries at the hospital or local level, which countries like Spain.

Eric Dube: So we think that there's still opportunity there to better understand where the unmet need is and who is above the key threshold. So that's gonna be a big part of what we're doing in parallel to clinical development at this time. And I'd say that it's an enzyme replacement therapy. So we'll continue to assess what the benchmarks are for pricing and what value we bring there. But we do believe that this is a significant opportunity for us, and we are currently first in development, and we are really focused on ensuring that lead position.

It's very important in ensuring optimal reimbursement and access and that was very important when we thought about the launch of <unk> and then we thought about someone who is going to be a great partner for us someone that's collaborative and it's going to have the focus on making <unk> the new treatment standard.

Third.

Within within Europe, and I think we certainly found that <unk> had all of what we were looking for.

Carter Lewis Gould: Thank you. And our next question comes from Carter Gould from Barclays. Your line is now open.

So we felt like it was also the right time for us to make that decision because there was quite a bit of work that needs to be done not just to ensure filings with regulators, but dossiers for HCA and ensuring that we prepare the organization and the infrastructure.

Carter Lewis Gould: This is Justin. I'm for Carter. Thanks for taking the call.

Carter Lewis Gould: Thank you for taking the question and congratulations on all the progress this quarter. Just one quick wrap up question for us on PEG to Batinase.

And education, and so that's what led us to making that decision and we think that we're in a really great place with thought with before and I think what we have.

Carter Lewis Gould: Understanding that you don't want to be sort of too revealing about what data you expect to show in the readout, but Eric, you mentioned earlier that duration of response is going to be sort of a key criteria in your moving forward decisions. I'm just wondering if you can tell us how much duration data we should expect in this first readout and how much that's going to impact. You know, your next steps with the program and, sort of, if you're going to be waiting on any more duration data going forward before you move ahead with the program.

As I alluded to in my prepared comments is two organizations with <unk>.

Exquisite focus.

In that.

That same goal of making <unk>, the new kind of treatment foundation for Iga nephropathy, and <unk> and we think that that really does.

De risk the execution risk that comes with any launch.

So.

That answers your question and Bill I'll turn it over to you on how we.

We've discussed that combined file with the EMA.

Carter Lewis Gould: Sure. Yeah, I'll ask Bill to talk a little bit about what we're going to be looking at and what the trial design will allow in terms of, you know, follow-up. Yeah, so from a duration perspective, we'll have double-blind data from everybody in the interim up through 12 weeks.

Yes, certainly and thanks for the question.

We have discussed this with the Eni in there along with our approach for the combined decision.

Working at the current time schedule.

Pre MAA meeting to go through the interim analysis data and align on the content of the submission, but they are aware and aligned with the approach.

Carter Lewis Gould: But then those patients go on to continue in an open-label extension.

Carter Lewis Gould: So, for many of the patients, we'll have significantly longer windows of time for that. As is often true in metabolic disease with biochemical endpoints, there's a degree of variability that is certainly aided when you look at a longer window of ascertainment. So, the trial design is very strong for that.

We're good to go there.

Yeah.

And thank you.

And our next question comes from Laura Chico from Wedbush Security.

Your line is now open.

Thanks, very much for taking the question and I apologize if I am not sure how they'll jump off for a second but I had a question. Just recently you guys did.

Operator: Thank you. And if you have a question, that is star number one. Again, if you have a question...

Kind of contrasting the U S versus the European regulatory strategy. So if I'm understanding things correctly, Dan could be submitted in the first quarter 'twenty to its success.

Timothy Francis Lugo: Tim Lugo, William Blair Hey guys, this is Walker Unlocked with Tim. Thanks for taking the questions.

Timothy Francis Lugo: So I was just wondering, Eric, if you could maybe provide a bit more color on the process behind choosing V4 as your partner in Europe, you know, what their infrastructure is and why that makes them the ideal partner for you and Scarfenton. And then, as well, on the EMA application, have you discussed with the EMA the idea of submitting the combined applications, and Dan. What's the feedback on that?

Festival with the additional data from duplex duplex.

<unk> can be submitted in the middle of 'twenty, two I thought I heard you say that.

There was an advantage to filing these submissions.

They're in the European case, I'm, just curious why it might not make sense to file these together in the U S setting.

Eric Dube: Okay, sure. So Lachlan, thanks so much for the questions. I'll take the first one on really how our thinking evolved to select V4 as our partner, and then I'll ask Bill to talk a little bit more about our engagements with the EMA. So as we set out to assess the value of partnering in Europe for Sparcentin, it led us to think about who has an established presence within nephrology.

Sure.

So I'll ask bill to talk about that and really it's what both regulator regulatory agencies allow four pathways and that's really what's driven what ultimately is our strategy is how quickly can we get this out to as broad a population as possible bill.

Certainly I mean, it's a logical question from our standpoint, we have very strong interim trial results from protect and a very clear pathway forward that leads to a filing in the first quarter of 2022 for Iga nephropathy in the U S.

Eric Dube: And when we think about that, it's not just having relationships with nephrologists, which V4 clearly has; they have relationships not just with the majority of nephrology practices within Europe but also with some of the top KOLs. They also have experience of working with regulators and with HTA bodies, not just nationally but also regionally and in some countries at the hospital or local level, which is very important in countries like Spain in ensuring optimal reimbursement and access.

Wait for the additional Egfr data.

And then reviewed that with the agency in order to support a similar filing for <unk> with the FDA and what we don't want to do is wait that extra period of months and hold back the Iga nephropathy submission in the U S. We can submit in <unk>.

Eric Dube: And that was very important when we thought about the launch of SparCenten. And then we thought about someone who's gonna be a great partner for us, someone that's collaborative and is gonna have the focus on making SparCenten the new treatment standard within Europe. And I think we certainly found that V4 had all of what we were looking for. And so we felt like it was also the right time for us to make that decision because there was quite a bit of work that needed to be done, not just to ensure filings with regulators, but dossiers for HTAs, and ensuring that we prepared the organization, the infrastructure, and education.

Parallel were slightly offset.

Basically cross referenced between two active NDA within the European system.

There isn't a mechanism by which we can do that so if we.

To optimize our strategy there by combining the two hygiene.

Hi, Jay Nephropathy, and SSG is once the data are available that allows us to get sports center and two the most the largest number of patients the quickest in that geography, if we didn't do it that way we have to wait for one review to be completed before we can start the next or.

Eric Dube: And so that's what led us to make that decision, and we think that we're in a really great place with V4. And I think what we have, as I alluded to in my prepared comments, is two organizations with exquisite focus on that same goal of making SparCenten a new kind of treatment foundation for IgA nephropathy and FSGS. And we think that that really does de-risk the executional risk that comes with any launch. So hopefully, that answers your question. And Bill, I'll turn it over to you on how we discussed the combined file with the EA.

If we did parallel reviews, we ended up with two different trade lanes, which isn't ideal either.

So this is really two strategies with the same data.

That are optimized for the rules in their respective geographies.

Okay. That's that's helpful and if I could sneak in one quick follow up and again I apologize. If this has been asked but.

What is the risk to the U S submission.

<unk> delayed again.

Again submission.

The sink up with FX, Yes is there a potential for the agency to kind of change their position or kind of tried to combine their reviews.

William E. Rote: Yeah, certainly. Thanks for the question, Malcolm. We have discussed this with the EMA, and they're aligned with our approach for the combined decision. We're working at the current time to schedule a pre-MAA meeting to go through the interim analysis data and agree on the content of the submission, but they're aware and aligned with the approach, and so we're good to go there.

Sure Bill yes.

At this point.

Don't see that happening.

Early in development, we asked about combining the two indications into one.

And Indy, which would lead to one NDA.

And they preferred to keep the two separate two separate indications too.

<unk> to NDA.

Operator: And, thank you. And our next question comes from...

Part of that is driven by the fact that their metrics.

Laura Kathryn Chico: and Laura Chico from Wedbush Security.

And how they are able to justify resourcing. It comes down to how many reviews, they do and how many NDA. So it doesn't help them fight for resources, if they reduce the number of NDA. So artificially but it also decouple stem from a timing perspective.

Laura Kathryn Chico: Your line is now open.

Laura Kathryn Chico: Thanks very much for taking the question. And I apologize if I missed this. I'll have to drop off for a second.

Laura Kathryn Chico: But I had a question just with regard to kind of comparing the US versus European regulatory strategies. So if I'm understanding things correctly, IGAN could be submitted in the first quarter of 22. If successful with the additional data from duplex, FSGS could be submitted in the middle of 22. I thought I heard you say, though, that there was an advantage to filing these submissions together in the European case. I'm just curious why it might not make sense to file these together in the US setting.

I don't see.

Based on all the discussions that we've had within any indication that they would want to wait for subsequent data from.

From the <unk> study.

That's very helpful. Thank you.

<unk>. Thank you.

Laura Kathryn Chico: Sure, so I'll ask Bill to talk about that, and really, that's what both regulatory regulatory agencies allow for for pathways, and that's really what's driven you know what our strategy is, is how quickly can we get this out to as broad a population as possible. Bill? Certainly. I mean, it's a logical question.

And I'm showing no further questions I would now like to turn the call back to Chris Cline for closing remarks.

Alright. Thank you Justin This concludes our third quarter update. Thank you all for joining US. This afternoon to talk about our progress. We look forward to updating you further throughout the balance of the year and I Hope you all have a great evening.

Thank you. This concludes today's conference call. Thank you for participating you may now disconnect.

William E. Rote: From our standpoint, we have very strong interim trial results from PROTECT and a very clear pathway forward that leads to a filing in the first quarter of 2022 for hygiene and property in the U.S. We need to wait for the additional EGFR data and then review that with the agency in order to support a similar filing for FSGS with the FDA. And what we don't want to do is wait that extra period of months and hold back the IGA and the property submission. In the U.S., we can submit in parallel or slightly on set and basically have a cross-reference between two active NDAs. Within the European system, there isn't a mechanism by which we can do that.

[music].

No.

[music].

William E. Rote: So, to optimize the strategy there by combining the two, IGA Neuropathy, and FSGS once the data are available. That allows us to get sparsentine to the most, the largest number of patients, the quickest, in that geography. If we didn't do it that way, we would have to wait for one review to be completed before we can start the next, or if we did parallel reviews, we'd end up with two different trade names, which isn't ideal either. So this is really two strategies with the same data that are optimized for the rules in their respective geography.

Laura Kathryn Chico: Okay, that's helpful. I can sneak in one quick follow-up. And again, I apologize if this has been asked before, but what is the risk of the US submission being delayed for the IGAN submission to sync up with FSGS? Is there potential for the agency to kind of change their position or kind of try to combine the reviews? Thank you.

William E. Rote: Yeah, at this point, I don't see that happening. Early in development, we asked about combining the two indications into one IND, which would lead to one NDA, and they preferred to keep the two separate. Two separate indications, two INDs, and two NDAs. Part of that is driven by the fact that their metrics and how they are able to justify resourcing come down to how many reviews they do and how many NDAs they have. So it doesn't help them in a fight for resources if they reduce the number of NDAs artificially, but it also decouples them from the timing perspective. I don't see, based on all the discussions that we've had with them, any indication that this is true for subsequent data from the FSGS site.

Laura Kathryn Chico: That's very helpful. Thank you.

Christopher Cline: Thank you.

Christopher Cline: And I'm showing no further questions. I would now like to turn the call back to Chris Cline for closing remarks.

Christopher Cline: Great, thank you, Justin. This concludes our third quarter update. Thank you all for joining us this afternoon to talk.

Operator: Thank you all for joining us this afternoon to talk about our progress. We look forward to updating you further throughout the balance of the year, and I hope you all have a great evening. Thank you; this concludes today's conference call.

Operator: Today's conference call. Thank you for participating; you may now disconnect.

Operator: © BF-WATCH TV 2021 , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ??

Operator: Good day and thank you.

Operator: Thank you for standing by, and welcome to Travere Therapeu.

Operator: Therapeutics Third Quarter 2021 Financial Results and Corporate Update Calls. At this time, I'll

Operator: Participants are in a listen-only mode. Please be advised that this call is being recorded. If you require any further assistance, please press star zero.

Christopher Cline: I would now like to hand the conference over to Chris Cline, Senior Vice President, and best wishes.

Christopher Cline: Thank you, Justin. Good afternoon, and welcome to Travere Therapeutics' third quarter 2021 financial results and corporate update call. Thank you all for joining us. Today's call will be led by our Chief Executive Officer, Dr. Eric Dube. Eric will be joined for the prepared remarks by Dr. Noah Rosenberg, our Chief Medical Officer; 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.

Christopher Cline: Before we begin, I would like to remind everyone that statements major in 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.

Christopher Cline: Please see the forward-looking statement disclaimer in the company's press release issued earlier today, as well as the risk factors section in our Forms 10-Q and 10-K filed with the SEC.

[music].

Christopher Cline: In addition, any forward-looking statements represent our view only as of the date such statements are made, October 28, 2021.

Christopher Cline: And Travere specifically disclaims any obligation to update such circumstances that reflect future events.

Christopher Cline: www.thevenusproject.com With that, let me now turn the call over to Eric. Thank you, Chris. And, by the way, happy birthday today. Good afternoon, everyone.

Eric Dube: I am proud of the progress made across all facets of our business during the third quarter. First, I am pleased to report that we achieved several significant milestones related to our goal of positioning sparsentin to ultimately become the new treatment standard for IJ nephropathy and FSGS if approved. In August, we reported that our Pivotal Phase III PROTECT study of sparsentin in IJ nephropathy achieved its primary proteinuria endpoint with statistical significance at its pre-specified interminality.

Good day, and thank you for standing by and welcome to for the year Therapeutics third quarter 2021 financial results and corporate update call. At this time all participants are in a listen only mode. Please be advised that this call is being recorded.

Do you require any further assistance. Please press star zero I would now.

I would like to hand, the conference over to Chris Cline Senior Vice President of Investor Relations Corporate Communications. Please go ahead.

Eric Dube: The result exceeded our expectations by demonstrating a greater than three-fold reduction in proteinuria from baseline compared to those patients receiving the active control herbicide. And at the time of the interim assessments, Sparcentin was generally well-tolerated and consistent with the observed safety profile to date. This is the first time a single non-immunosuppressive agent has demonstrated this magnitude of effect on proteinuria reduction in a large, well-controlled

Thank you Justin good afternoon, and welcome to severe therapeutics third quarter 2021 financial results and corporate update call. Thank.

Thank you all for joining us today's call will be led by our Chief Executive Officer, Dr. Eric Today, Eric will be joined for the prepared remarks by Dr de Mello Rosenberger, Chief Medical Officer, Peter Herma, Our Chief commercial officer, and our Chief Financial Officer, Laura Clague.

Dr. Bill Rote senior Vice President of research and development will join us for the Q&A session.

Before we begin I would like to remind everyone that statements made during this call regarding matters that are not historical facts are forward looking statements within the safe Harbor provisions of the private Securities Litigation Reform Act of 1995 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.

Eric Dube: And we know from our engagement with the nephrology community that a treatment with these attributes is precisely what physicians are seeking to help prevent progression to end-stage kidney failure. I'm very pleased to report today that we've completed our pre-NDA interactions with the FDA for sparsentin in IJ nephropathy. Notably, the FDA agreed that the interim analysis from the PROTECT study supports submission of an application for accelerated approval under subpart A. Based upon the agency's feedback and alignment on our structure of the planned NDA, we expect to submit our application for accelerated approval in the U.S. in the first quarter of next year. We also made meaningful progress on our sparsentine program for FSGS during the quarter.

Expressed or implied by the statements.

Please see the forward looking statement disclaimer on the company's press release issued earlier today as well as the risk factors section of our Form 10-Q, and 10-K filed with the SEC. In addition, any forward looking statements represent our view only as of the date such statements are made October 28, 2021 trigger specifically disclaims any obligation to update such circumstances that reflect future information events or circumstances with that.

I'll now turn the call over to Eric Eric.

Thank you, Chris and by the way happy birthday today.

Good afternoon, everyone I am proud of the progress made across all facets of our business. During the third quarter first I am pleased to report that we achieved several significant milestones related to our goal of positioning <unk> to ultimately become the new treatment standard for Iga nephropathy and <unk>.

Eric Dube: Most importantly, we gained alignment with the FDA on our plan to provide the agency with additional EGFR data from the ongoing duplex study in the first half of 2022, which enables us to continue on the accelerated approval pathway for FSGS. If the additional EGFR data further strengthen the prediction of long-term benefit in the study, as we expect they should, we anticipate submitting an NDA for accelerated approval for FSGS in the middle of next year.

<unk> if approved in August we reported that our pivotal phase III protect study of <unk> in Iga nephropathy achieved its primary proteinuria endpoint with statistical significance and its pre specified interim analysis.

The result exceeded our expectations by demonstrating a greater than three fold reduction in proteinuria from baseline compared to those patients receiving the active control irbesartan.

Eric Dube: We are pleased that we now have a clear regulatory path to potential accelerated approval for sparsantin for both IgA nephropathy and FSGS in the U.S., and we look forward to achieving those submissions next year. I'm also pleased to share that we have formalized our plan to pursue a combined... IGA Nephropathy, and FSGS MAA submission for Sparsantan in Europe. This strategic decision will allow us to pursue the most expedited path to making sparsantin available for both IgA nephropathy and FSGS in Europe, and we believe it will increase the probability of success in achieving optimal market access across regions.

And at the time of the interim assessment <unk> was generally well tolerated and consistent with the observed safety profile to date.

This is the first time a single non immunosuppressive agent has demonstrated this magnitude of effect on proteinuria reduction and a large well controlled study.

And we know from our engagement with the nephrology community that a treatment with these attributes is precisely what physicians are seeking to help prevent progression to end stage kidney disease.

Very pleased to report today that we've completed our pre NDA interactions with the FDA for spar center in Iga nephropathy.

Notably the FDA agreed that the interim analysis from the protect study supports submission of an.

Application for accelerated approval under Subpart H.

Based upon the agency's feedback and alignment on our structure of the planned NDA, we expect to submit our application for accelerated approval in the U S. In the first quarter of next year.

Eric Dube: Additionally, this option allows us to potentially request an accelerated assessment for the review. We will continue our engagements with the EMA and expect the MAA application to be submitted mid-next year once the planned additional EGFR data from the duplex study can be incorporated, if supported. Also, as it relates to Europe, we were very pleased to recently enter into a joint collaboration and licensing agreement with V4Pharma for the commercialization of Sparsantan in Europe, Australia, and New Zealand.

We also made meaningful progress on our <unk> program for <unk> during the quarter. Most importantly, we gained alignment with the FDA on our plan to provide the agency with additional Egfr data from the ongoing duplex study in the first half of 2022, which enables us to continue on the accelerated approval pathway.

For <unk>, yes.

If the additional Egfr data further strengthen the prediction of a long term benefit in this study.

As we expect they should we anticipate submitting an NDA for accelerated approval for <unk> in the middle of next year.

Eric Dube: This collaboration aligns the strength of two leaders in rare nephrology with a shared mission to make Sparsentin the new treatment standard for IJ nephropathy and FSGS if approved. And it significantly increases our probability of success across all launches, as it will allow us to have the dedicated focus needed for successful launches in these substantial markets. The collaboration also recognizes the value Sparcentin can bring to Europe and strengthens our financial foundation, with potential milestone payments totaling up to $845 million and royalties on sales in these regions of up to 40%.

We are pleased that we now have a clear regulatory path to potential accelerated approval for <unk> for both Iga nephropathy and <unk> in the U S and we look forward to achieving those submissions next year.

I'm also pleased to share that we have formalized our plan to pursue a combined.

<unk> nephropathy, and <unk> MAA submission for <unk> in Europe.

This strategic decision will allow us to pursue the most expedited path to making <unk> available for both Iga nephropathy and <unk> in Europe, and we believe it will increase the probability of success for achieving optimal market access across regions.

Eric Dube: We look forward to working closely with V4 as they integrate Sparcentin into their portfolio and prepare for potential launches in Europe, Australia, and New Zealand beginning in 2023. Beyond Sparsentin, we continue to be encouraged by the potential for our novel PEG-dibatinase program in classical homocystinuria, or HCU.

Additionally, this option allows us to potentially request accelerated assessment for the review process.

We will continue our engagements with the EMA and expect the MAA application to be submitted mid next year. Once the planned additional egfr data from the duplex study can be incorporated if supportive.

Also as it relates to Europe, we were very pleased to recently enter into a joint collaboration and licensing agreement with <unk> for pharma for the commercialization of <unk> in Europe, Australia, and New Zealand.

Eric Dube: We believe that it has the potential to become the first disease-modifying therapy for the more than 7,000 people in the U.S. and Europe who are not adequately responding to current treatment. We remain on track for a preliminary assessment from the ongoing Phase 1-2 trial, now named the Compose Study, before year-end. And we look forward to establishing next steps for the program if the data are as encouraging as we expect. Lastly, I'd like to highlight the performance of our commercial organization in the third quarter.

This collaboration aligns the strength of two leaders in rare nephrology.

With a shared mission to making sports center, the new treatment standard for Iga nephropathy, and <unk>, if approved and it significantly increases our probability of success across all launches as it will allow us to have the dedicated focus needed for successful launches in the substantial markets the collaborations.

<unk> also recognizes the value <unk> can bring in Europe, and strengthened our financial foundation with potential milestone payments totaling up to $845 million and royalties on sales in these regions of up to 40%.

Eric Dube: Our execution led to another quarter of year-over-year growth across all approved products, despite the ongoing challenging environment created by the COVID-19 pandemic. This performance underscores our confidence in the ability to successfully deliver Sparsantan and PEG-2BATvasive. Let me now turn the call over to Noah for the clinical update.

We look forward to working closely with before they integrate <unk> into their portfolio and prepare for potential launches in Europe, Australia, and New Zealand beginning in 2023.

Beyond <unk>, we continue to be encouraged by the potential for our novel pegged <unk> program in classical home assistant urea or <unk>, we believe that it has the potential to become the first disease modifying therapy for the more than 7000 people in the U S and Europe, who are not adequate.

Noah Rosenberg: Thank you, Eric. I remain very pleased with the progression of our pipeline of potential first-in-class therapies for people living with rare diseases. In the third quarter, we took meaningful steps towards advancing Sparcentin towards potential approvals in both Igena Properties and FHPS. Most notable during the quarter were the positive top-line interim results from the ongoing pivotal Phase III sex study of sparsankin in myogenic properties. After 36 weeks of treatment, patients receiving Sarc10 achieved a mean reduction in protein area from baseline of 49.8% compared to a mean reduction in protein area from baseline of 15.1% for all Sarc10 treated patients.

Responding to current treatment options.

We remain on track for a preliminary assessment from the ongoing phase one two trial now named are composed study before year end.

And we look forward to establishing next steps for the program. If the data are encouraging as we expect.

Lastly, I'd like to highlight the performance of our commercial organization in the third quarter, our execution led to another quarter of year over year growth across all approved products. Despite the ongoing challenging environment created by the COVID-19 pandemic.

Noah Rosenberg: This result was clinically meaningful and statistically significant, with a p-value of less than 0.0001. Furthermore, preliminary EGFR data available at the time of the interim analysis were consistent with our powering and indicative of a potentially clinically meaningful treatment effect after two years of treatment. And from a safety perspective, we continue to be encouraged that the time of the interim assessment for assent appeared to be generally well tolerated, and it appeared consistent with the previously observed safety profile.

This performance underscores our confidence in the ability to successfully deliver sparse centered and picked about makes if approved let me now turn the call over to Noah for the clinical update no.

Yes.

Thank you Eric.

We remain very pleased with the progression of our pipeline of potential first in class therapies for people living with rare diseases.

The third quarter, we took meaningful steps towards advancing <unk> towards potential approvals in both Iga nephropathy and FX, yes.

Notable during the quarter, where the positive top line interim results from the ongoing pivotal phase III study of <unk>.

Noah Rosenberg: These data build upon a robust data path that has helped shape Sparsantian's safety profile and demonstrated the potential for clinically meaningful primary reductions across nearly 500 patients with IG Nephropathy and FSGF, including several patients that have been on therapy more than seven years in the open-label extension of the Phase II duet study.

Iga nephropathy.

After 36 weeks of treatment patients receiving <unk> achieved a mean reduction in proteinuria.

Baseline.

49 <unk>.

8%.

Impaired to a mean reduction in proteinuria from baseline of 15, 1%.

Irbesartan treated patients.

Noah Rosenberg: This further supports our confidence that Sporcentan has the potential to meet the clear need for a new therapeutic option to meaningfully reduce progneria over and above widely used ACE inhibitor and ARB treatments and to do so while avoiding the long-term safety challenges associated with immune suppression. As Eric mentioned earlier, we recently completed our three NDA interactions for IGNephropathy, and we are very pleased with the successful outcome. The FDA's agreement that the interim analyses from the PROTECT study support submission of an application for accelerated approval under subpart 8 was clear.

This result was clinically meaningful and statistically significant with a P value.

What's been point, Oh, Oh Oh.

<unk>.

Preliminary egfr data available at the interim.

The interim analysis.

Consistent with our salary and indicative of a potentially clinically meaningful treatment effect after two years of treatment.

I'm a safety perspective, we continue to be encouraged.

<unk> of the interim assessment.

It appeared to be generally well tolerated and it appeared consistent with previously observed safety profile.

These data built upon a robust data package.

Noah Rosenberg: With this feedback in alignment with the content and organization of our application, we will be continuing our NDA preparations with the expectation of submitting it in the first quarter of next year. Our FSGS program also continued its forward momentum with the recent Taipei interaction, where we gained alignment with the FDA on our plan to provide the agency with additional HFR data in the first half of next year to support a potential application for accelerated approval.

Helped shape sports and safety profile as demonstrated the potential for clinically meaningful reductions.

Cross nearly 500 patients with Iga nephropathy, and <unk>, Inc.

Including several patients that have been on therapy more than seven years and the open label extension of the phase two duet study.

This further supports our confidence in <unk>.

It has the potential to meet the clear need for a new therapeutic option to meaningfully reduce proteinuria over to Paul.

Noah Rosenberg: At the time of the planned EGFR data cut, all patients remaining in the duplex study will have completed at least one year of treatment, and approximately 50% of patients will have completed two years of treatment. We believe at this time point, the data will have sufficient maturity to strengthen the prediction for long-term benefit. If the data meet these expectations, we anticipate submitting an NDA mid-next year for accelerated approval of SPARS-N10 for SSGS in the U.S. In parallel, we'll be working on the combined IJNephropathy and FSGS MAA application for conditional marketing authorization of Sparsantan in Europe, with the expectation of submitting that application mid-next year as well.

We use ace inhibitor and ARV treatments.

To do so while avoiding the long term safety challenges associated with immune suppression.

As Eric mentioned earlier, we recently completed our pre NDA interactions for Iga nephropathy, and we are very pleased with the successful outcome.

The Fda's agreement that the interim analysis for the protect study support submission of an application for accelerated approval under Subpart H was clear.

This feedback and alignment on the content and organization of our applications, we will be continuing our NDA preparations with the expectation of submitting in the first quarter of <unk>.

Next year.

Our <unk> program also continued its forward momentum with the recent type of interaction, where we gained alignment with the FDA on our plan to provide the agency with additional Egfr data in the first half of next year to support a potential application for accelerated approval.

Noah Rosenberg: Both the PROTECT and the DUPLEX studies continue to advance, and based upon the progress of these studies, are well-positioned to make the playoffs in their confirmatory endpoints in 2023. Lastly, on the pipeline, our optimism for the Peg-to-Botany program remains high as it continues to advance through the Phase I-II Composed Study. COMPOSE is a dose escalation study designed to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and clinical effects of pentobatinase in patients with HCU.

At the time of the planet Egfr data.

All patients remaining in the duplex study will have completed at least one year of treatment and.

And approximately 50% of patients will have completed two years of treatment.

We believe at this time point the data, we'll have sufficient maturity to strengthen the prediction for long term benefit.

Noah Rosenberg: Patients in the study are being followed for up to 12 weeks in a blinded fashion in each cohort before entering an open-label extension, and we are anticipating a preliminary assessment from the study before year end. When we evaluate the preliminary data, we'll be examining a few factors. First, as you would expect with any early study of this nature, it's safe. We'll be looking for any signals of interest, including immune response. Next, there is early evidence of efficacy.

If the data meet these expectations.

Anticipate submitting an NDA mid next year.

Accelerated approval of <unk> for FCS in the U S.

In parallel we will be working on the combined Iga nephropathy and Atlas yes.

A application for conditional marketing authorization of <unk> in Europe with.

What's the expectation of a submission mid next year as well.

Noah Rosenberg: We know that for those patients who are B6 non-responsive, treating physicians typically target patients below 100 microvolts of total homocysteine. If PEG-2 batonase can get patients below this level, we believe it could have the potential to become a clinically meaningful new treatment option.

Both the protect and duplex studies continue to advance.

Based upon progress of these studies.

Our well positioned.

Yes.

Exploratory end point in 2023.

Lastly on the pipeline our optimism for the pace of that and this program remains high.

Peter Heerma: When we provide our update later this year, we'll look to provide insight into some of these areas of focus. I'll now turn the call over to Peter for the commercial update.

As it gets used to advance through the phase one to compose study.

Compose is a dose.

Escalation study designed to assess the safety Tolerability pharmacokinetics, pharmacodynamics and clinical effects of <unk> in patients with HCM.

Peter Heerma: Thank you, everyone, and good afternoon. We continue to be very pleased with our commercial organization's performance, especially in this environment where virtual HCP interactions remain commonplace. And we still see that fewer patients are visiting their physicians compared to pre-pandemic times. In the third quarter, our execution resulted in 6% organic growth in net product sales over the same period last year. This was driven by underlying demand and strong patient compliance across all products.

Patients in this study are being followed for up to 12 weeks in a blinded fashion and each cohort before entering an open label extension.

We are anticipating a preliminary assessment from the study.

For year end.

When we evaluate the preliminary data we will be examining a few factors.

First as you would expect with any early study of this nature is safety.

We will be looking for any signals of interest including immune response.

Peter Heerma: For our Stiola products, we continue to see new patients initiate treatment, and to date, we have experienced limited impact from the generic version of the original formulation that entered the market in the prior quarter. Despite the limited impact thus far, we do still anticipate an adverse impact on Viola sales in the quarters ahead.

Next.

It is early evidence of efficacy, we know that for those patients who are <unk> nonresponsive treating physicians typically it's hard getting patients below 100 micro bowls.

Total home equities.

That needs to get patients below this level, we believe it could have the potential to become a clinically meaningful new treatment option.

Peter Heerma: Our focus will remain on identifying new patients, ensuring access to therapy, and providing the important services and support that many patients need to potentially be stone free. The Bile Acid Postural also continues to perform in line with our expectations. As a result of the strong performance of the commercial portfolio over the last two quarters, we anticipate ending the year with low to mid-single-digit growth in net product sales. Given the COVID-19 pandemic and the evolving dynamics, this would be a meaningful achievement and further bolster the confidence in our team's abilities going into a critical period of anticipated launches for Spartan.

When we provide our update later this year, we will look to provide insight into some of these areas of focus.

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

Thank you Bella.

Good afternoon.

We continue to be very pleased with our commercial organizations performance, especially in this environment. We have virtual HCP interactions remain commonplace, we still see that fewer patients are visiting their physicians compared to pre pandemic times.

In the third quarter.

Execution, we sold 6% organic growth.

Product sales over the same period last year.

This was driven by underlying demand and strong patient compliance across the whole product.

Peter Heerma: We are planning for the launches of SPAR Center in both IGA and FHDS in the U.S. We anticipate the first ones to now be in IJN Frappuccino, and we have an incredibly exciting opportunity in front of us.

For our style of products, we continue to see new patients initiate treatment and to date, we have experienced limited impact from the generic version of the original formulation.

The market in the prior quarter.

Despite the limited impact plus four we do still anticipate an adverse impact on our sales in the quarters ahead.

Peter Heerma: In the U.S. alone, we believe there are between 30,000 and 50,000 patients living with IgA nephropathy that would be good candidates for Sporacentum at launch, if approved. And we believe that opportunity is likely to increase meaningfully over time with greater awareness and diagnosis. We are well-positioned to embark on our journey to reach this space. We will be growing our organization from a position of strength by scaling our proven infrastructure in rare nephrology to expand our call centers and provide the services and support we know are critical for patients living with rare diseases.

Our focus will remain on identifying new patients ensuring access to therapy and providing the important services can support many patients need to potentially be stone free.

The bile acid portfolio also continues to perform in line with our expectations.

As a result of the strong performance in the commercial portfolio over the last two quarters, we anticipate ending the year with low to mid single digit growth in net sales over 2020.

Given the COVID-19, pandemic and the evolving dynamics it could be a meaningful achievements and further bolster our confidence in our team's abilities going into a critical period of anticipated launches for Spartan.

Peter Heerma: And in market research studies with nephrologists, prior to the product data readouts, we learned that paracetamol has an emerging product profile that rises to the top of the most desirable programs in development. Given the strength of the interim data from PROTECT and the positive feedback that we have received from the nephrology community since our top line announcement, we are confident that if approved, we will be in a strong position to ultimately establish Sparcentum as the new treatment standard for IGA nephropathy.

We have plenty for launches of Spartan in both Iga nephropathy and <unk> in the U S.

We anticipate the first loss to now be in.

Proxy and we have an incredibly exciting opportunity in front of us.

In the U S alone. We believe there are between 30% and 50000 patients living with Iga nephropathy.

Would be good candidates for sparse and some headlines.

Bruce.

And we believe the opportunity is likely to increase meaningfully overtime with greater awareness and diagnosis.

Peter Heerma: Overall, I have great confidence in our team's ability to add Sparcentum to our multi-year track record of delivering life-changing therapies to people living with rare diseases. And I look forward to sharing more about our progress as we continue to prepare the organization for the potential upcoming launches. I will now turn the call over to Laura for the financial update.

We are well positioned to embark on our journey to reach these basins.

We will be growing our organization from a position of strength can.

Can you make our infrastructure around the strategy to expand our coal plants and provide the services and support we know are critical for patients living with rare diseases.

And in market research studies with Nephrologist price to protect data Readouts, we lose that's far simpler hasnt emerging product profile that rises to the top of the most desirable programs in development.

Laura Clay: For the third quarter of 2021, we reported net product sales of $54.2 million from our commercial portfolio compared to $51.1 million for the same period in 2020. We reported a gap net loss of $35.6 million for the third quarter of 2021. After adjusting for non-cash expenses and income tax, we reported a non-gap net loss of $7.9 million for the third quarter of 2021. On a gap basis, R&D expenses were $48.4 million for the third quarter of 2021. The increase compared to 2020 is largely attributable to increased patient numbers.

Given the strength of the interim data from protect and the positive feedback we have received from the nephrology community since our topline announcements we are confident that if a <unk>.

We will be in a strong position to ultimately establish spar symptom is the new treatment standard for Iga nephropathy.

Overall, I have great confidence in our team's ability to add.

Our syndrome to our multi multiyear track record of delivering life changing therapies to people living with rare diseases and I look forward to be sharing more about our progress as we continue to prepare the organization put a potential upcoming launches.

Laura Clay: Thank you for your attention and involvement in the ongoing studies of sparsentine as well as in the advancement of the PEG-tobatinase program in HCU.

Let me now turn the call over to Laura for a financial update.

Laura.

Thank you Peter.

For the third quarter of 2021, we reported net product sales of $54 2 million from our commercial portfolio compared to $51 one for.

Laura Clay: $45.2 million for the third quarter of 2021. Relevant non-cash expenses for the third quarter included $3.2 million in stock-based compensation and amortization, on a gap basis.

At the same period in 2020.

We recorded a GAAP net loss of $35 6 million for the third quarter of 2021.

After adjusting for noncash expenses and income tax we reported a non-GAAP net loss of $7 9 million for the third quarter of 2021.

Laura Clay: Administrative expenses for the third quarter were $36.1 million. The increase compared to 2020 is largely attributable to an increased headcount of people at the company.

On a GAAP basis, R&D expenses were $48 4 million for the third quarter of 2021.

The increase compared to 2020 is largely attributable to increased patient enrollment in the ongoing studies of <unk> as well as advance advancement of to take that next program in HCM.

Laura Clay: Operational Growth and Professional Feeds, on an adjusted basis

Laura Clay: SG&A expenses for the third quarter were $25.5 million. Significant non-cash adjustments for the quarter consisted of $10.6 million in stock-based compensation and depreciation and amortization. We ended the quarter in a strong financial position with $551.2 million in cash and cash equivalents. This balance includes the $55 million upfront payment we received as part of the joint venture.

On an adjusted basis R&D expenses were $45 2 million since third quarter of 2021.

Relevant noncash expenses for the third quarter included $3 2 million stock based compensation and amortization.

On a GAAP basis, selling general and administrative expenses for the third quarter were $36 1 million.

Kris compared to 2020 is largely attributable to increased head count go to the company's operations and professional fees.

On an adjusted basis SG&A expenses for the third quarter were $25 5 million.

Laura Clay: This is part of the joint collaboration and licensing agreement with B4 Pharma that was entered into during the quarter.

Significant noncash adjustments for the quarter consisted of $10 6 million in stock based compensation and depreciation and amortization.

Laura Clay: For the balance of this year, we expect modest increases in our operating expenses. As we look further out, we anticipate significant investments throughout next year as we prepare for multiple potential product launches and continue to support the ongoing studies of Sparcentin.

We ended the quarter in a strong financial position with $551 2 million in cash and cash equivalents.

Balance includes the $55 million upfront payment, we received as part of the joint collaboration licensing agreement with <unk> pharma. It was entered into during the quarter.

Laura Clay: Thank you for your attention and for advance our Peg-to-Baton-Ace program. Taking into account the potential impact of the generic formula, but not including additional business development, we anticipate...

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

As we look further out we anticipate significant investments throughout next year as we prepare for multiple potential product launches continue to support the ongoing studies of <unk> and <unk>.

The answer to that program.

Eric Dube: Participate in this cash balance to support our planned operations into 2023. Now, I'll hand the call back over to Eric for his closing comments.

Taking into account the potential impact of generics.

But not including additional business development, we anticipate this cash balance to support our planned operations into 2023.

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

Eric Dube: Thank you, Laura. I couldn't be more pleased with our organization's execution in the third quarter. We delivered impressive results from the Pivotal Phase 3 PROTECT study. We made considerable regulatory progress across our Spar Centen program, entered into a collaboration agreement with a global leader in nephrology to maximize the value of sparsentin in Europe, Australia, and New Zealand, and we continue to effectively deliver our approved products to patients in need. With the regulatory pathways for IJ nephropathy and FSGS now set, we will be working in earnest to prepare three high-quality NDA and MAA applications to be submitted next year. And we will continue our steps to prepare our organization to execute on successful launches of Sparcentin if approved.

Thank you Laura I couldnt be more pleased with our organization's execution in the third quarter. We delivered impressive results from the pivotal phase III protect study.

We made considerable regulatory progress across our <unk> programs.

Entered into a collaboration agreement with a global leader in nephrology to maximize the value of <unk> in Europe, Australia, and New Zealand and we continue to effectively deliver our approved products to patients in need.

With the regulatory pathways for Iga nephropathy, and <unk> now set we will be working in earnest to prepare three high quality NDA and MAA applications to be submitted next year and.

And we will continue our steps to prepare our organization to execute on successful launches of <unk> and if approved.

Eric Dube: Lastly, a few weeks ago, we announced the planned transition for NOAA to an executive advisor role at the end of this year. I'd like to take this opportunity to thank him for all of his contributions in getting us to this strong position. We look forward to working closely with Noah to ensure a smooth transition in the coming months and in his new role next year as we continue to advance our clinical studies and prepare our NDA and MAA applications. Thank you, Noah. Let me now turn the call over to Chris for Q&A. Okay, Chris?

Lastly, a few weeks ago, we announced the planned transition for Noah to an executive advisor role at the end of this year.

I'd like to take this opportunity to thank him for all of his contributions and getting us to this strong position. We look forward to working closely with Noah to ensure a smooth transition in the coming months and his new role next year as we continue to advance our clinical studies and prepare our NDA and MAA applications.

Thank you Noah.

Let me now turn the call over to Chris for Q&A Kris.

Christopher Cline: Great. Thank you, Eric. Justin, can we go ahead and open up the lines for Q&A, please?

Great. Thank you Eric Jonathan can we go ahead and open up the lines for Q&A. Please.

Operator: Thank you. As a reminder, to ask a question, you'll need to press star 1 on your telephone. To withdraw your question, press the pound key.

Thank you as a reminder to ask a question you will need to press star one on your telephone to withdraw.

All your question, perhaps the balance sheet. Please standby, we compile the Q&A roster and again that is star one if you'd like to ask a question.

Operator: Please stand by. We'll compile the Q&A roster. And again, that is Star 1 if you'd like to ask a question. And our first question is going to come from Maurice Raycroft from Jeffries. Your line is now open. Hi everyone, congrats on the update and happy birthday, Chris.

First question is going to come from Maury Raycroft from Jefferies. Your line is now open.

Hi, everyone. Congrats on the update and happy birthday, Chris.

Yes.

Maurice Thomas Raycroft: My first question is, if you can talk more about the IgA nephropathy pre-NDA meeting and say if it was the more mature EGFR data relative to FSGS that enabled FDA to concur that the interim analyses were adequate for submission, and can we assume that because of this IgA nephropathy regulatory update, we can have more confidence that FSGS data will mature?

I. My first question is if you can talk more about the Iga nephropathy pre NDA meeting and save if it was the more mature egfr data relative to <unk>. She asked that enable the FDA to concurred that the interim analyses were adequate for submission and could we assume that because of this iga nephropathy.

Regulatory update that we can have more confidence at FSC assay that will mature similarly.

Maurice Thomas Raycroft: SGS data will mature similarly.

Thanks, so much for the questions I'll turn that one over to bill.

William E. Rote: Maury, thanks so much for the questions. I'll turn that one over to Bill.

Yeah. Thanks, Thanks for the question Maury.

William E. Rote: Yeah, thanks. Thanks for the question, Maury. The EGFR picture for Tech Study does represent a more mature data set, and that comes from a couple of things. Mostly, the enrollment dynamics were very different. Recall that the PROTECT Study began about six months behind the DUPLEX Study, so the work building the infrastructure was done on the DUPLEX Study, and the PROTECT Study was drafted in behind. So with linear, much more linear enrollment dynamics, we had a much greater fraction of the data set that was out in the later time points.

Egfr picture for the protect study does represent a more mature data set that comes from a couple of things predominantly.

The enrollment dynamics were very different recall that the protect study began about six months behind the.

Duplex study so the work building the infrastructure was done on the duplex study in the protect study drafted in behind it. So we have a linear much more linear enrollment dynamics, we had much greater fraction.

The dataset that was out in the later time points and that was in Stark contrast to what we saw with the protect study.

William E. Rote: And that was in stark contrast to what we saw with the PROTECT study. To your other, the other aspect of your question and competence building for FSGS, I think that when we look across the program, for Sentinel in three efficacy studies in two diseases, and has performed very consistently across those studies. So when you allow the picture to mature in duplex, our expectation is that it's going to come in line and will meet our expectations. We'll have the data cut in the spring, and that will... That will give us Patty. Great. And maybe one follow up. If you just remind what your expectations are for the review period for for both

To your other the other aspect of your question and confidence building for <unk> I think that when we look across the program four centers in three efficacy studies in two diseases and has performed very consistently across those studies. So when you.

You allow the picture to mature.

<unk>, our expectation is that it's going to come in line.

And we will meet our expectations, we will have the data cut in the spring and that will.

That will give us that answer.

Great.

Maybe one follow up if you could just remind what your expectations are for their review period.

William E. Rote: for both programs, for FSGS and Hygiene and Property.

For for both programs for <unk> and Iga nephropathy.

William E. Rote: So, for the PROTECT study, we will be requesting priority review. So, if we submit in the first quarter, then we, if we are granted priority review, which we certainly believe this disease and this drug warrant it with this data set, that would mean we'd have an answer from the agency, a PDUFA date, before the end of 22. For FFGS, we expect to submit that in the middle of the year, next year following interaction with the FDA on EGFR cut.

So for the protect study we will be requesting priority review. So if we submit in the first quarter than we if we are granted priority review, which we certainly believe this.

This disease and this drug warranted with this dataset.

That would mean, we'd have an answer from the agency at Paducah date before the end of 'twenty two.

For <unk>, we expect to submit that in the middle of the year next year following <unk>.

Interaction with the FDA on Egfr cotton should those data for filing that would be a mid year.

William E. Rote: And should those data support filing, that would be a mid-year 22 filing. So priority would put that in the first half of 2020, 3, and if it's standard review, it would be early in the second half of 2020. Great. Okay, congrats again, and thanks for taking my questions.

22 filings so priority would put that in the first half of 'twenty.

Three.

If it's standard review it would be early in the second half.

Great. Okay, Congrats again and thanks for taking my questions.

Sure thing Thank you Mark.

Greg Harrison: And thank you. And our next question comes from Greg Harrison from Bank of America. Your line is now open.

And thank you and our next question comes from Greg Harrison from Bank of America. Your line is now open.

Greg Harrison: Good afternoon, guys. Thanks for taking our questions. The first one is on PEG2BATnase.

Good afternoon, guys. Thanks for taking our questions.

First one is on pegged to that nice.

Greg Harrison: What is the extent of the data that we could expect to see in the coming readout? And what would you consider to be clinically meaningful there? And then, assuming it is, what would be the next steps for this program if the data are supportive of moving forward?

What is the extent of the data that we can expect to see in the in the coming readout.

And what would you consider to be clinically meaningful there.

And then assuming that it is what would be the next steps for this program.

If the data are supportive of moving forward.

Eric Dube: Yeah, so thanks so much, Craig, for the questions. I'll take the first one on what we can expect, and then I'll ask Bill to share a little bit more about the next steps. So, as Noah mentioned, we're really looking at a couple of key areas with this analysis from the COMPOSE study. First and foremost, this is the first study in humans, so we wanna have a particular eye on safety. The second aspect is to really understand the dose response in this trial, given that we are studying different dose cohorts.

I'll ask bill to share a little bit more around the next steps so as as Noah mentioned, we're really looking at a couple of key areas with this analysis from the composed study first and foremost. This is the first study in humans. So we want to have a particular eye on safety.

Second aspect is to really understand the dose response in this trial given that we are studying different dose cohorts.

Eric Dube: And then the third, and I think particularly around your question of what would be considered clinically meaningful, is to assess whether patients are able to get below 100 micromolars for total homocysteine urea and whether they're able to stay below those levels. That is considered the treatment goal in the guidelines and by clinicians and patients with homocystinuria.

And then the third and I think particularly around your question of what would be considered clinically meaningful is to assess whether patients are able to get below 100 micro molar for total home assistant urea and whether they're able to stay below those levels that is considered.

The treatment goal in the guidelines and by clinicians and patients.

Eric Dube: And so, you know, we're gonna be particularly looking at that threshold. And, you know, we'll obviously continue to assess that, but those are the major areas of focus as we go into that analysis. And I'll turn it over to Bill to talk about next steps. Thanks, Eric.

With home assistant urea, and so we're going to be particularly looking at that threshold.

And we'll obviously continue to assess that but those are the major areas of focus as we go into that analysis.

And I'll turn it over to Bill to talk about next steps.

William E. Rote: Yeah, the first step will be to analyze the data from the interim analysis, and we expect to share that, at least to some degree. The next immediate step is really to use that data set and engage with regulators. And that will be the results from the interim analysis of the composed study, as well as the current data from the natural history study. We'll then take their input and do our own feasibility analyses and work toward developing a plan for the next clinical study.

Thanks, Eric.

The first step will be to analyze the data from the interim interim analysis, and we expect to share that at least to some degree the <unk>.

Next immediate step is really to use that data.

Dataset and engage with regulators and that'll be the results from the interim analysis of the proposed study as well as the.

Current data from the natural history study.

We'll then take their input into our own feasibility analyses and work toward developing a plan for the next clinical study in parallel to that we'll be working on manufacturing scale up and process development.

William E. Rote: In parallel to that, we'll be working on manufacturing scale-up and process development. The goal is ultimately going to be to move downstream from the composed study into a pivotal study in that next phase of development, and we'll be able to share more about that once we've had those engagements with the NIH.

It goes ultimately going to be to move downstream from the proposed study into a pivotal study.

And that next phase of development, and we will be able to share more about that once we have had those engagements with the acos.

Greg Harrison: Great, that's helpful. And then, if I could sneak in one more, as far as the IGAN program is concerned, would you expect that there would be an ADCOM needed there?

Okay. That's helpful and then if I can sneak in one more.

As far as the.

Again program would.

Would you expect that there would be an AD com needed there.

William E. Rote: One of the questions we asked in our pre-NDA interactions was their perspective on whether or not we would have an ADDCOM. The agency said that based on the data they've seen thus far, they don't anticipate calling for an advisory committee. We're not surprised by that, given the data from the interim analysis, and we see that as a positive. That said, these things can change, and we'll be prepared should an ADDCOM be called, but at this point, we don't expect to have it.

Bill.

One of the questions. We asked in our pre NDA interactions was their perspective on whether or not we would have an ad com.

The agency said that based on the data they've seen thus far they don't anticipate calling for an advisory committee.

We're not surprised with that given the data from the interim analysis and we see that as a positive that said these things can change and we'll be prepared should and Ed can be called but at this point, we don't expect to have one.

Greg Harrison: Great, very helpful. Thanks again, and congrats again on all the

Great very helpful. Thanks, again, and congrats again on all the progress.

Greg Harrison: Thank you. And our next question comes from Joseph Schwartz from SVB Larynx. The line is now open.

Thank you Greg.

And thank you.

And our next question comes from Joseph Schwartz with SBB Leerink. Your line is now open.

Joseph Patrick Schwartz: Hi, thanks very much. I was wondering...

Hi, Thanks, very much I was wondering if you'll be reporting any more data to investors at that time that you perform your next interim analysis of the duplex study.

Joseph Patrick Schwartz: If you will be reporting any more data to investors at the time that you perform your next interim analysis of the duplex study.

In the first half of.

'twenty two or.

Joseph Patrick Schwartz: Will all of the information just be for the...

We will all of the information just be for the FDA and likewise, what we hear whether the FDA has any feedback for the company on your plan to file as occurred when you performed your first interim analysis.

Joseph Patrick Schwartz: for the FDA. And likewise, will we hear whether the FDA has any feedback for the company on your plan to fight it?

Eric Dube: This kind of file occurred when you performed your first interim analysis. Joe, thanks so much for the questions. So as part of our interactions and plans for that additional EGFR cut, we're going to be working with the FDA on any disclosure plans. I would say it's probably safe to assume that we would not be providing any additional data given that the trial is ongoing and we continue to be very focused on maintaining that blind and the trial integrity.

Joe Thanks, so much for the questions. So as part of our interactions and plans for that additional Egfr cut we're going to be working with the FDA on any disclosure plans I would say, it's probably safe to assume that that we would not be providing any additional data given that it's the trials on.

Going and we continue to be very focused on maintaining that blind and the trial integrity.

Eric Dube: Really, what we're going to be focusing on in large part is communication following the meeting once we receive the minutes or once we have submitted or accepted the NDA to FDA. And so that really is going to be our focus as we look at the additional data. But as I've mentioned, we're going to be working with FDA to see what they are comfortable with us disclosing at that point.

Really what we're going to be focusing on in large part is to communicate following the meeting once we receive minutes or once we have submitted or accepted.

The FDA.

And so that really is going to be our focus as we look at those additional data, but as I've mentioned, we're going to be working with FDA to see what they are comfortable with us disclosing at that point.

Joseph Patrick Schwartz: Great, thanks for the color. And then how would you rate the awareness and the appreciation of protein area lowering as an important treatment goal in the community?

Great. Thanks for the color.

And then how would you rate the awareness and appreciation of proteinuria lowering as an important treatment goal in the community physicians, who see the most <unk> and Iga nephropathy patients how ready is the market to adopt a proteinuria lowering agent like as far as <unk> Pan and how much education do you still need to.

unknown: Transcribed by https://otter.ai

unknown: Ready Is The Market To Adopt A Protein Area Lowering Agent Like Spars and Tan?

Sure.

Under take in order to encourage strong uptake in the real world.

Eric Dube: Yeah, thanks for that question. I'll have both Peter and Noah answer that given that Peter's team is working very much on a lot of the market research with a broader nephrology community. Noah and his team are with some of the top nephrologists, and they can provide a bit of feedback on what they are hearing. Peter, do you want to start?

Yeah. Thanks for that question I'll have both Peter and Noah.

Answer that given that Peter's team is working very much on a lot of market research with the broader nephrology community knowing his team with some of the top nephrologist and they can provide a bit of feedback on what they are hearing Peter you want to start.

Yeah, Thanks, Eric and thank you Joe for the question.

Peter Heerma: Yeah, thanks Eric and thanks Jo for the question. Well, what we learned from the market research as well as the thought leaders that we are speaking with is that proteinuria is often the market that results in treatment initiation and monitoring of patients, and how well they're doing, which I think makes sense because proteinuria is also the strongest predictor of progression. So I think there is a well-established understanding of proteinuria and its relation to progression of disease, in particular a patient at higher risk for dialysis. No, I don't know if you want to build upon that. Yeah, yeah.

Have we learned from the <unk>.

Research as well as the thought leaders that we are speaking with proper Julia.

Awesome.

The market is that if we sold to treatment initiation and monitor monitoring.

How well they are doing.

We think it makes sense because proteinuria is also the strongest predictor of progression of disease.

So I think there is a well established.

Understanding of proteinuria and its relation to progression of disease in particular.

<unk> <unk> from higher risk towards dialysis.

So if you want to build upon that.

Yes.

Noah Rosenberg: Yeah. Yeah. I think that's right, Peter.

Alright.

I think that's right Peter.

Noah Rosenberg: I think physicians, nephrologists specifically, are acutely aware of the toxic effects of proteinuria. You know, we speak to them at AdWords all the time, and they're aware of the concern that proteinuria will drive worsening outcomes and ultimately hasten dialysis and the need for immunoreplacement therapy. I think where the education comes in is now that we have additional therapy and potential therapy, it's around targets, educating around those targets, where they can realistically go because they've really had such limited options until now.

I think physicians neurologists, specifically are acutely aware of the toxic effects of proteinuria.

We speak to the outboard is all the time.

They are aware of the concern that proteinuria will drive worsening outcomes and ultimately patients dialysis the need for renal replacement therapy.

The education comes in is now that we had additional therapy and a potential therapies around targets educating around those targets, where they can realistically go because it really had such limited options until now specifically at <unk> for instance.

Noah Rosenberg: Specifically, in IgAN, for instance, your choices are very limited. ACEs and ARBs, as we know, often fail. And immunosuppressants are very limited in that they can create concerns around safety. They're short-term treatments, and they often don't work.

This is a very limited aces and arbs, we know often fail and immune suppressants are very limited in that they can create concerns around.

Youre short term treatments and they often don't work so I think awareness of <unk> and the mechanism how it works.

Noah Rosenberg: So I think awareness around Sporcentin, the mechanism, how it works, and the safety data set is really important that we get the message out there that, realistically, with a drug like Sporcentin, there's a better chance of them achieving some of these targets that have been set out by the guidelines. So I think that that's certainly an area that we're focused on. Sounds good. Thanks for taking my questions and best wishes to NOAA. Thank you. And our next question comes from Michelle Gilson.

The safety data set is really important because we get the message out there that realistically, what's the truck makes more sense and there's a better chance of them achieving some of these targets that have been set up by the guidelines. So I think that that's certainly an area that we're focused on.

Sounds good thanks for taking my questions and best wishes to Noah.

Thanks Keith.

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

Michelle Gilson: and Michelle Gilson from Canaccord Genuity. Your line is now open.

Michelle Gilson: Hi. Thank you for taking my question. I guess I was wondering if you could provide a little bit more color around your pre-NDA meeting and, you know, what the FDA was most focused on. And, I guess, more specifically, what EGFR analyses were done and presented to the agency for IGAN. And I know we've discussed in the past that there are different ways that you can evaluate changes in

Hi, Thank you for taking my question.

I guess I'm wondering if you could provide a little bit more color around your pre NDA meeting and what the FDA was most focused on and I guess more specifically what Egfr analyses were done and presented to the agency.

Again.

I know we've discussed in the past that there are different ways that you can evaluate changes in egfr.

So and.

Hi.

So I think that I heard you earlier alluded to priority.

Michelle Gilson: Thanks, Michelle. Bill, would you like to take those questions? Sure. I think I, I think I've got them all jotted down.

Review timelines for IBM and I was just curious if that was discussed during our pre NDA meeting.

Thanks, Michele Bill would you like to take those questions.

Sure I think I I think I've got them, all jotted down as far as.

William E. Rote: As far as what was presented to the Agency for the Pre-MDA Interactions, the briefing book presented a comprehensive summary of the interim analysis. For example, proteinuria measured multiple different ways or expressed in different ways, EGFR versus time split by groups at a summary level, both observed, and then the MMRM, which is the primary analysis endpoint, and additionally, a summary view of safety and adverse events. So, that was how the analyses were presented.

What was presented to.

The agency for the pre NDA interactions the briefing book presented a comprehensive summary of the interim analysis. So it was proteinuria measured multiple different ways or expressed different ways Egfr versus time split by groups and a summary level both observed in the <unk>.

<unk>, which is the primary analysis endpoint.

And additionally.

Some review of safety and adverse.

Events, so that was.

The analysis presented.

William E. Rote: Your question around priority review. We certainly believe that this is an ideal case for priority review, but that's not something that gets granted at this stage of the game. We intend to request it, and we see this as an ideal case for it, but we won't know the answer to that question until after we've submitted the NDA in the first quarter.

Your question around priority review.

Certainly believe that this is an ideal case for priority review.

That's not something that gets granted at this stage of the game, we intend to request it.

And we see this as an ideal case for it but we won't know the answer to that question until after we've submitted the NDA in the first quarter.

William E. Rote: Okay, and then, you know, one, if I can unpack that as well, you know, you're evaluating different dose levels now, and you've indicated that you're...

Okay and then.

One if I cannot think of that as well.

You're evaluating different dose levels now and you've indicated that you may evaluate another go slabaugh.

I'm just curious.

William E. Rote: I'm just curious if you expect that you'll evaluate different dose intervals at another dose level, or if it's just, I guess, higher doses?

If you expect that you will evaluate different dose intervals at another dose level.

Yes.

I guess.

William E. Rote: Yeah, we have said that within this study, we're looking both at dose regimens and dose levels. We will make the decision on what we're going to do with the next cohort when we see the data in December. So it could be either of those, or it could be staying at the same level of dose and increasing the amount of experience at the current level. So it's going to be a data-driven decision once we're unblinding at the interim in later this year.

Higher dose.

Bill.

Yes.

We have said that within this study we're looking both the dose regimen and dose levels.

We will make the decision on what we're going to do with the next cohort when we see the data in December so it could be either of those or it could be state.

Staying at the same level of dose and increasing the amount of experience at the at the current level. So.

Going to be a data driven decision once were on blinding at interim.

William E. Rote: Okay, if I could just follow up. Are there any issues with going up in volume here? I know it's a sub-two dose, but you know, if you do evaluate a higher dose.

Later this year.

Oh, Okay, if I could just.

Follow up is there any I guess.

Yeah.

Are there any issues with going up in volume here.

Two dose.

If you do evaluate a higher dose.

William E. Rote: So there are limits to how much is tolerable on an individual sub-2 injection. As you increase in dose, depending on the solubility of the agent that you're working with, there can be limits there. It becomes a balance between patient need and what's based on that.

So there are limits to how much is tolerable on an individual's sub Q injection.

As you increase in dose depending on the solubility of the agents that youre working with.

Yeah.

There can be limits there it becomes a balance.

Between patient need and what's patient, what's acceptable with patients, but one of the easy ways to deal with that.

William E. Rote: What's acceptable with patients. But one of the easy ways to deal with that is to split the injection if you are going to higher doses or higher volumes into multiple substitute injections. And that.

Split the injection, if you are going to higher doses or higher volume.

It's a multiple sub two injections in that.

William E. Rote: And that tends to ameliorate the issue. Okay, thank you.

Tends to ameliorate the issue.

Okay. Thank you guys. So much for taking my questions.

Michelle Gilson: Thank you guys so much for taking my questions. Sir. Sir.

Certain shock.

And thank you.

Liisa Ann Bayko: And our next question comes from Liisa Bayko from Evercore ISI.

And our next question comes from Lisa Baker from Evercore ISI.

Liisa Ann Bayko: Hi, I guess congratulations are in order for both Chris and Noah. So congratulations to you both.

Your line is now open.

Hi.

Congratulations are in order for both Chris and Noah So congratulations to you both and.

Liisa Ann Bayko: And I've been fielding a lot of questions on HCU, and we've been doing a lot of work on it. And I think the main question I'm getting is just like how much information investors are going to get when you kind of preview some data. So can you maybe just elaborate on what our expectations are appropriately set about what kind of information you're going to get and how, you know, how much you can kind of like, you know, communicate, you know, what you're seeing in terms of response in patients.

I think fielding a lot of questions on HCM with getting a bunch of work on it.

And I think the main question I'm getting is just like how much information investors aren't going to get when you do kind of preview. Some data. So can you maybe just elaborate just so expectations.

Our set appropriate lists of what kind of information you're going to get and how you know how much you can kind of like you know communicate what youre seeing in terms of response in patients.

Eric Dube: Sure. I'll take that one, Liisa.

Sure I'll take that one Lisa and our focus again is on those three areas of safety dose response and magnitude of effect on total home assisting theyre of course or other measures of efficacy that we're looking at for example in defining as a biomarker that is often assess.

Eric Dube: And, you know, our focus again is on those three areas of safety, dose response, and magnitude of effect on total homocysteine. But there, of course, are other measures of efficacy that we're looking at. For example, methionine is a biomarker that is often assessed within HCU.

Within HCA use so we're going to be looking at those aspects as well.

Eric Dube: So we're going to be looking at those aspects as well. I'd say the expectation is that, you know, we want to make sure that we provide clarity on each of those questions once we have the data readout. But we've not yet committed to whether or not we're going to be disclosing how much data at that time, given that, you know, one, it's a competitive space, and we want to make sure that we're not providing so much so as to lose the lead that we have in this space.

I'd say the expectation.

Is that we want to make sure that we provide clarity on each of those questions. Once we have the data readout.

But we've not yet committed to weather.

Data, we're going to be disclosing at that time, given that one is the competitive space and we want to make sure that we're not <unk>.

Providing so much so as to lose the lead that we have in this space, but we also want to make sure that we really have a good understanding of what that dose.

Eric Dube: But we also want to make sure that we really have a good understanding of what that dose, you know, that dose and dose regimen is, and, you know, whether we believe that we have the right dose. We certainly wouldn't want to communicate efficacy if we believe that there's something else, you know, more that we could be pursuing. So that's a little bit of how we're thinking about it. We said that, at a minimum, we'd provide a qualitative update on each of those three questions. But we could very well be in a position to provide, you know, more specific data as we move forward.

That dose and dose regimen is and whether we believe that we have the right dose, we certainly wouldn't want to.

Communicate efficacy if we believe that there is something more that we could be pursuing so that's a little bit of how we're thinking about it.

We said that at a minimum will provide a qualitative update on each of those three questions, but we very well could be in a position to provide.

More specific data.

Liisa Ann Bayko: And any kind of additional color on timing?

As we move forward.

And then the.

And they kind of additional color on timing.

Eric Dube: Well, we're on track to be able to provide that update sometime later this year. But to be able to narrow that down even further, I would say we're just not at that point to do so. But we are very near.

Well, we're on track to be able to provide that update.

Sometime later this year, but.

To be able to narrow that down even further.

We're just not at that point to do so, but we're very near.

Eric Dube: Okay, and then just finally on the same program, you know, kind of when I look at it, I think it could be at least as big of an opportunity as Bar-Santan, and in terms of its value, because it has a pretty long, like, revenue tail, it actually could be pretty valuable as a, you know, relative to Bar-Santan, more valuable, actually. Can you maybe comment on how you're thinking about kind of the size of the opportunity and provide some benchmarks? Well, we certainly are excited about the

Okay and then just finally on the on the same program.

Kind of what I look at it I think it could be at least as big of an opportunity as far as Santana in terms of its value.

Because it has a pretty long like revenue tail, it actually could be pretty valuable.

As a relative.

Relative to the percent in more valuable actually can you maybe comment on how you're thinking about kind of.

The size of the opportunity and provide some benchmark.

Well, we certainly are excited about the opportunity given that there is a high unmet need here.

Eric Dube: Well, we certainly are excited about the opportunity given that there is a high unmet need here. The addressable population, if we start there, is 7,000 patients currently across the U.S. and Europe. But I think we recognize that there are a few areas that really can be improved, which we believe, you know, is typically the case within rare diseases. One is that these patients are oftentimes undiagnosed despite newborn screening. Many of these patients are still not diagnosed early enough and go into adulthood before being effectively diagnosed.

The addressable population if we start there is 7000 patients currently across the U S and Europe, but I think we recognize that there are a few areas that really can be approved which we believe is typically the case within rare disease. One is that these patients are oftentimes on diagnosed does.

Despite newborn screening many of these patients still are not.

Diagnosed early enough and go into adulthood before being effectively diagnosed.

Eric Dube: And you know, while there are other therapies like high-dose vitamin B6. The literature states that there is a proportion of up to 50% that are responsive. However, when we talk to experts in this area, they are very clear that that is a very high estimate of B6 responsiveness.

And while there are other therapies like high dose vitamin B six.

The literature states that there is.

Proportion of up to 50% that are responsive when we talk to experts in this area.

They are very clear that that.

That is a very high estimate of six responsiveness. So we think that there's still opportunity there to better understand where the unmet need is and who was above the key thresholds. So that's going to be a big part of what we're doing in parallel to clinical development.

Eric Dube: So we think that there's still opportunity there to better understand where the unmet need is and who is above the key threshold. So that's gonna be a big part of what we're doing in parallel to clinical development at this time. And I'd say that it's an enzyme replacement therapy, so we'll continue to assess what the benchmarks are for pricing and what value we bring there. But we do believe that this is a significant opportunity for us, and we are currently first in development, and we are really focused on ensuring that lead position.

At this time and I'd say that it's a it's an enzyme replacement therapy. So we'll continue to assess what the benchmarks are for pricing and what value. We bring there, but we do believe that this is a significant opportunity for us and we are.

We are currently first in development and we are really focused on ensuring that lead position.

Carter Lewis Gould: Thank you. And our next question comes from Carter Gould from Barclays. Your line is now open.

Thank you very much thanks.

Thanks Lisa.

Thank you.

Our next question comes from Carter Gould from Barclays. Your line is now open.

Carter Lewis Gould: from Barclays, your line is now open. Hi, this is Justin on behalf of Carter.

Hi, This is Justin on for Carter, Thanks for taking the question and congrats on all the progress this quarter.

Carter Lewis Gould: Thanks for taking the question. And congrats on all the progress this quarter. Just one quick wrap up question for us on peg to batinase, understanding that you don't want to be sort of too revealing on what data you expect to show in the readout. But Eric, you mentioned earlier that duration of response is going to be sort of a key criteria in your moving forward decisions. And just wondering if you can tell us how much duration data we should expect in this first readout, how much that's going to impact your, you know, your next steps with the program, and sort of, you know, if you're going to be waiting on any more duration data going forward before you move ahead with the program.

Just one quick wrap up one for us on pegged at that nice understanding that.

I want to see.

Sort of to revealing on what data you expect to show on the readout, but Eric you mentioned earlier that duration of response is going to be sort of a key criteria and youre moving forward decisions I'm. Just wondering if you can tell us how much duration data we should expect in this first readout, how much that's going to impact.

Your next steps with the program.

So.

If you are going to be waiting on any more duration data going forward before you move ahead with the program.

Carter Lewis Gould: Sure. Yeah, I'll ask Bill to talk a little bit about what we're going to be looking at and what the trial design will allow in terms of, you know, follow-up. Yeah, so from a duration perspective, we'll have double-blind data from everybody in the interim, up through 12 weeks. But then those patients go on to continue.

Sure Yeah I'll.

I'll ask bill to talk a little bit about what we're going to be looking at and what the trial design will allow in terms of.

Follow up.

Yes, so from a from a duration perspective, we'll have double blind data from.

From everybody in the interim through 12 weeks.

And those patients go on to continue is an open label extension. So are many of the patients will have significantly longer.

Carter Lewis Gould: to continue is an open label extension.

Carter Lewis Gould: So for many of the patients, we'll have to have.

unknown: [inaudible]

Operator: and thank you, and if you have a question that is star one again, if you have a question that is star one, and our next question comes from Tim Lugo from William Blair, your line is now open. Hey guys, this is Walker Unlocked with Tim. Thanks for taking the questions.

Windows 10 for that so.

As is often true in metabolic disease.

<unk> biochemical endpoints there is a degree of variability.

It's certainly aided what you look with a longer window of ascertainment. So the trial design is very strong for that.

Awesome. Thank you very much.

Thanks, Jess and thank you.

Timothy Francis Lugo: Again, if you have a question, that is star 1. And our next question comes from Tim Lugo from William Blair. Your line is now open. Hey guys, this is Lachlan from Team Tim. Thanks for taking the questions.

And if you have a question that is star one again, if you have a question that is star one and our.

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

Hey, guys. This is work on them.

Good question.

I was just wondering Eric if you can maybe.

A bit more color on the process behind choosing to pay for the partner in Europe.

What their infrastructure.

Why that makes sense.

Timothy Francis Lugo: Have you discussed with the EMA the idea of submitting the combined applications? And yeah, what's the feedback on that?

Ideal partner.

It's about that Tim.

And then as well.

On the <unk> application.

Discuss with the EMA.

Yes Darren.

Submitting the combined application.

Eric Dube: Okay, sure. So Lachlan, thanks so much for the questions. I'll take the first one on really how our thinking evolved to select V4 as our partner. And then I'll ask Bill to talk a little bit more about our engagements with the EMA. So as we set out to assess the value of partnering in Europe for Sparcentin, it led us to think about who has an established presence within nephrology.

Yes.

The payback on that.

<unk>.

Okay sure.

So lachlan thanks, so much for the questions I'll take the first one on really how are how we're thinking evolved to select before as our partner.

And then I'll ask bill to talk a little bit more about our engagements with the EMA.

So as we set out to assess.

The <unk>.

Value of partnering in Europe with <unk>.

Really it led us to think about who has an established presence within nephrology and when we think about that it's not just having the relationships with Nephrologist, which V. For clearly has they have relationships not just with a majority of nephrology practices within Europe, but also with some of the top.

Eric Dube: And when we think about that, it's not just having relationships with nephrologists, which V4 clearly has; they have relationships not just with the majority of nephrology practices within Europe but also with some of the top KOLs. They also have experience of working with regulators and with HTA bodies, not just nationally but also regionally and in some countries at the hospital or local level, which, you know, is very important in ensuring optimal reimbursement and access.

Kols. They also have experience in working with regulators and with HCA bodies, not just nationally, but also regionally and in some countries at the hospital or local level, which countries like Spain.

Is very important in ensuring optimal reimbursement and access and that was very important when we thought about the launch of <unk> and then we thought about someone who is going to be a great partner for us someone that's collaborative and it's going to have to focus on making <unk> the new treatment standard.

Eric Dube: And that was very important when we thought about the launch of Sparcentin. And then we thought about someone who'd be a great partner for us, someone that's collaborative and is going to have the focus on making Sparcentin the new treatment standard within Europe. And I think we certainly found that V4 had all of what we were looking for. And so, you know, we felt like it was also the right time for us to make that decision because there was quite a bit of work that needed to be done, not just to ensure filings with regulators, but dossiers for HTAs and ensuring that we prepared the organization, the infrastructure, and education.

Third.

Within within Europe, and I think we certainly found that <unk> had all of what we were looking for.

And so we felt like it was also the right time for us to make that decision because there was quite a bit of work that needs to be done not just to ensure filings with regulators, but dossiers for <unk> and ensuring that we prepare the organization of the infrastructure.

Eric Dube: And so, you know, that's what led us to make that decision, and we think that we're in a really great place with V4. What we have, as I alluded to in my prepared comments, is two organizations with exquisite focus on that same goal of making Sparcentin a new kind of treatment foundation for IgA nephropathy and FSGS.

In education and so.

It's what led us to making that decision and we think that we're in a really great place with with before and I think what we have.

As I alluded to in my prepared comments is two organizations with <unk>.

Exquisite focus.

In.

That same goal of making <unk>, the new kind of treatment foundation for Iga nephropathy, and <unk> and we think that that really does.

William E. Rote: And we think that that really does de-risk the executional risk that comes with any launch. So hopefully, that answers your question. And Bill, I'll turn it over to you on how we discussed the combined file with the EMS. Yeah, certainly. Thanks for the question, Malcolm. We have discussed this with the EMA, and they are aligned with our approach to the combined decision. We're working at the current time to schedule a pre-MAA meeting to go through the interim analysis data and agree on the content of the submission. But they're aware and aligned with the approach, and so we're good to go there.

De risk the execution risk that comes with any launch.

So.

That answers your question and Bill I'll turn it over to you on.

We've discussed that combined file with the EMA.

Certainly thanks for the question Michael we have discussed this with the EMEA and they are aligned with our approach for the combined decision.

Working at the current time to schedule.

Pre MAA meeting to go through the interim analysis data and align on the content of the submission, but they are aware of and aligned with the approach.

We're good to go there.

Operator: And thank you.

And thank you.

Laura Kathryn Chico: And our next question comes from Laura Chico from Wedbush Security.

And our next question comes from Laura Chico from Wedbush Security.

Laura Kathryn Chico: Your line is now open.

Laura Kathryn Chico: Thanks very much for taking the question. And I apologize if I missed this; I'll have to drop off for a second.

Your line is now open.

Thanks, very much for taking the question and I apologize if I am not sure how they'll jump off for a second but I had a question just with regard to kind of contrasting the U S.

Laura Kathryn Chico: But I had a question just with regard to kind of comparing the US versus European regulatory strategies. So if I'm understanding things correctly, IGAN could be submitted in the first quarter of 22. If successful with the additional data from duplex, FSGS could be submitted in the middle of 22. I thought I heard you say, though, that there was an advantage to filing these submissions together in the European case. I'm just curious why it might not make sense to file these together in the US setting.

S versus the European regulatory strategy, so if I'm understanding things correctly again could be submitted in the first quarter of 'twenty two if successful with the additional data from duplex duplex SGS could be submitted in the middle of 'twenty two I thought I heard you say, though that there was an ads.

Vantage to filing a submission together.

In the European case, I'm, just curious why it might not make sense to file these together in the U S setting.

William E. Rote: Sure, so I'll ask Bill to talk about that, and really, that's what both regulatory regulatory agencies allow for for pathways, and that's really what's driven you know what our strategy is, is how quickly can we get this out to as broad a population as possible. Bill? Certainly. I mean, it's a logical question.

Sure.

I'll ask bill to talk about that and really it's what both regulator regulatory agencies.

Allow four pathways and that's really what's driven will ultimately as our strategy is how quickly can we get this out to as broad a population as possible bill.

Certainly I mean, it's a <unk>.

William E. Rote: From our standpoint, we have very strong interim trial results from PROTECT and a very clear pathway forward that leads to a filing in the first quarter of 2022 for hygiene and property in the U.S. We need to wait for the additional EGFR data and then review that with the agency in order to support a similar filing for FSGS with the FDA. And what we don't want to do is wait that extra period of months and hold back the IGA and the property submission.

Logical question from our standpoint, we have very strong interim trial results from protect and a very clear pathway forward that leads to a filing in the first quarter of 'twenty to 'twenty two for Iga nephropathy in the U S.

Wait for the additional Egfr data.

And then reviewed that with the agency in order to support a similar filing for <unk> with the FDA and what we don't want to do is wait that extra period of months and hold back the Iga nephropathy submission in the U S. We can submit in paas.

William E. Rote: In the U.S., we can submit in parallel or slightly offset and basically cross-reference between two active NDAs. However, within the European system, there isn't a mechanism by which we can do that. So, to optimize the strategy there by combining the two, IGA Necropathy, and FSGS once the data are available. That allows us to get Sparcentin to the most, the largest number of patients with quick, in that geography. If we didn't do it that way, we would have to wait for one review to be completed before we can start the next, or if we did parallel reviews, we'd end up with two different trade names, which isn't ideal either. So this is really two strategies with the same data that are optimized for the rules in their respective geographies.

<unk> were slightly offset.

Basically cross referenced between two active NDA within the European system, there isn't a mechanism by which we can do that so if we.

To optimize the strategy there by combining the two.

Hygiene nephropathy and SSG is once the data are available that allows us to get <unk> to the most the largest number of patients quickest in that geography.

We didn't do it that way we have to wait for one review the completed before we can start the next one.

Or if we did parallel review as we ended up with two different trade lanes, which isn't ideal either.

So this is really two strategies with the same data.

That are optimized for the rules in their respective geographies.

Laura Kathryn Chico: Okay, that's helpful. I can sneak in one quick follow up. And again, I apologize if this has been asked before, but what is the risk of the US submission being delayed and the IGAM submission to sync up with FSGS? Is there potential for the agency to kind of change their position or kind of try to combine the reviews?

Okay. That's helpful. And then I can sneak in one quick follow up and again I apologize. If this has been asked but.

What is the risk to the U S submission.

<unk> delayed again submission.

To sync up with FX, Yes is there a potential for the agency to kind of change their position or kind of tried to combine the reviewed thank you.

William E. Rote: Thank you. Bill?

William E. Rote: Yeah, at this point, I don't see that happening. Early in development, we asked about combining the two indications into one IND, which would lead to one NDA, and they preferred to keep the two separate. Two separate indications, two INDs, and two NDAs. Part of that is driven by the fact that their metrics and how they are able to justify resourcing come down to how many reviews they do and how many NDAs they have. So it doesn't help them in a fight for resources if they reduce the number of NDAs artificially, but it also decouples them from a timing perspective. I don't see, based on all the discussions that we've had with them, any indication that this will be the case for subsequent data from the FSGS study.

Sure Bill.

At this point.

Don't see that happening.

Early in development, we asked about combining the two indications into one.

And <unk>, which would lead to one NDA.

And they preferred to keep the two separate two separate indications too.

<unk> to NDA as part of that is driven by the fact that their metrics.

And how they are able to justify resourcing. It comes down to how many reviews, they do and how many NDA. So it doesn't help them fight for resources, if they reduce the number of NDA, so artificially but it also decoupled them from a timing perspective.

I don't see.

Based on all the discussions that we've had within any indication that they would want to wait.

For subsequent data from.

William E. Rote: That's very helpful. Thank you. Thank you.

From the <unk> study.

That's very helpful. Thank you.

Christopher Cline: And I'm showing no further questions. I would now like to turn the call back to Chris Cline for a closing remark.

<unk>. Thank you.

And I'm showing no further questions I would now like to turn the call back to Chris Cline for closing remarks.

Christopher Cline: Great. Thank you, Justin. This concludes our third quarter update. Thank you all for joining us.

Alright. Thank you Justin This concludes our third quarter update. Thank you all for joining US. This afternoon to talk about our progress. We look forward to updating you further throughout the balance of the year and I Hope you all have a great evening.

Christopher Cline: Thank you all for joining us this afternoon to talk about our progress. We look forward to updating you further throughout the balance of the year, and I hope you all have a great evening.

Operator: Thank you. This concludes today's conference call. Thank you for participating. You may now disconnect.

Thank you. This concludes today's conference call. Thank you for participating you may now disconnect.