Q1 2021 Travere Therapeutics Inc Earnings Call

[music].

Hello, and welcome to the <unk> Therapeutics first quarter financial results and corporate update my name is Brandon and I'll be your operator for today.

Brandon: My name is Brandon, and I'll be your operator for today. At this time, all participants are in a listen-only mode.

At this time all participants are in a listen only mode. Later, we will conduct a question and answer session during which you may dial star one if he has a question. Please note. This conference is being recorded and I will not turn it over to Chris Clark you may begin Sir.

Brandon: Later, we will conduct a question-and-answer session during which you may tell us, Star 1, if you have a question. Please note this conference is being recorded, and I will not turn it over to Chris Klein. You may begin, sir.

Christopher Cline: Great, thank you, Brandon. Good afternoon, and welcome to Treveer Therapeutics' first quarter 2021 financial results and corporate update call. Thank you for joining us. I hope you all remain well. Today's call will be led by our chief executive officer, Dr. Eric Today. Eric will be joined for prepared remarks by our chief medical officer, Dr. Noah Rosenberg, Peter Herrmann, our chief commercial officer, and our chief financial officer, Laura Clegg. Dr. Bill Wright, Senior Vice President of Research and Development, will join us for the Q&A session.

Great. Thank you Brandon good afternoon, and welcome to <unk> Therapeutics first quarter 2021 financial results and corporate update call.

Thank you for joining us I hope you all remain well today's call will be led by our Chief Executive Officer, Dr. Eric Today, Eric will be joined from the prepared remarks by our Chief Medical Officer, Dr. Noah Rosenberg, Peter Paramount, Our Chief commercial officer, and our Chief Financial Officer, Laura Clague Dr.

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 Security Litigation Reform Act of 1995. Forward-looking statements are not guarantees of performance. They involve known and unknown risks, uncertainties, and assumptions that may cause actual results, performance, and achievements to differ materially from those expressed or implied by the statement.

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

Forward looking statements are not guarantees of performance they involve known and unknown risks uncertainties and assumptions that may cause actual results performance and achievements to differ materially from those expressed or implied by the statements. Please see the forward looking statement disclaimer on the company's press release issued earlier today as well as the risk factors section on our form 10-Q, and 10-K filed with the SEC and.

Christopher Cline: Please see the forward-looking statement disclaimer in the company's press release issued earlier today, as well as the risk factor section in our forms 10Q and 10K filed with the SEC. In addition, any forward-looking statements represent our views as of the date such statements are made, May 6, 2021. Intervieur specifically disclaims any obligation to update such statements to reflect future information, events, or circumstances. Let me not turn the call over to Eric. Eric.

In addition, any forward looking statements represent our views as of the date such statements are made may six 2021 contributor specifically disclaims any obligation to update such statements to reflect future information events or circumstances, Let me now turn the call over to Eric Eric.

Eric Dube: We remain dedicated, Sorry, technical difficulties. We remain dedicated to the key priorities that we believe will enable us to strengthen our position of leadership in the rare disease community, and the first quarter of this year was another example of our organization's ability to execute.

We remain dedicated.

Sorry technical difficulty.

We remain dedicated to the key priorities that we believe will enable us to strengthen our position of leadership in the rare disease community in the first quarter of this year was another example of our organization's ability to execute.

For us this centers on developing our pipeline for potential first in class programs targeting rare diseases that have significant unmet need.

Earlier this year. The every life Foundation published the National economic burden of rare disease study.

Eric Dube: For us, this centers on developing our pipeline for potential first-in-class programs targeting rare diseases that have significant unmet needs. Earlier this year, the Every Life Foundation published the National Economic Burden of Rare Disease Studies. The study found that on average, it takes approximately 6.3 years for a person living with a rare disease to find a diagnosis, and that patients typically see upwards of 17 specialists along their diagnostic journey. Overall, the study estimated that the direct medical costs associated with rare diseases in the U.S. will be more than $400 billion in 2019.

The study found that on average it takes approximately six three years per person living with a rare disease defined the diagnosis.

And that patients typically see upwards of 17 specialists along their diagnostic journey.

Overall, the study estimated that the direct medical costs associated with rare diseases in the U S with more than $400 billion in 2019.

This is especially relevant given the challenges the rare nephrology community faces due to the limited innovation over the past few decades for diseases like <unk> and Iga nephropathy.

For example, <unk> is considered to have one of the worst prognosis.

Amongst primary preliminary other diseases.

It is estimated that more than 50% of <unk> patients with persistent net product area will reach end stage kidney disease within 10 years.

This translates to over 2000 people each year, reaching <unk> related end stage kidney disease in the U S.

Eric Dube: This is especially relevant given the challenges the rare nephrology community faces due to limited innovation over the past few decades for diseases like FSGS and IJ nephropathy. For example, FSGS is considered to have one of the worst prognoses among primary glomerular diseases. It is estimated that more than 50% of FSGS patients with persistent nephrodite proteinuria will reach end-stage kidney disease within 10 years. This translates to over 2,000 people each year reaching FSGS-related end-stage kidney disease in the U.S.

Patients today have a long diagnostic journey experienced progressive loss of kidney function and become dependent upon transplant in dialysis.

This is why we have great urgency in pursuing our goal of developing <unk> to become a new treatment standard for <unk> and Iga nephropathy if approved.

We remain encouraged by the interim proteinuria data that we reported from the duplex study in February.

The data showed that treatment with <unk> resulted in a 60% greater relative likelihood of achieving FTR when.

When compared to Irbesartan.

The data also showed that percentage has been generally well tolerated and overall the safety profile between treatment groups in the study at the time of the analysis were generally comparable which is encouraging.

Eric Dube: Patients today have a long diagnostic journey, experience progressive loss of kidney function, and become dependent upon transplant and dialysis. This is why we have great urgency in pursuing our goal of developing sparsentin to become a new treatment standard for FSGS and IJ nephropathy if approved. We remain encouraged by the interim protenuria data that we reported from the Duplex study in February. The data showed that treatment with sparsentin resulted in a 60% greater relative likelihood of achieving FPRE when compared to herbicide.

We are in the process of engaging with regulatory agencies to discuss potential accelerated approval submission for <unk> yet.

As such we will not be in a position to provide a regulatory update today, but remain on track to do so as planned before the end of the first half of the year.

In parallel our protect study of <unk> in Iga Nephropathy continues to advance and is nearing completion of enrollment.

The study continues to receive broad support from the nephrology community and for patients and their families.

Shortly we remain on track for a top line readout from the interim proteinuria assessment in the third quarter of this year.

And we look.

Two the data from protect we remain encouraged by the consistency with which <unk> has demonstrated its ability to meaningfully reduce proteinuria throughout its development we.

Eric Dube: The data also showed that sparsentin has been generally well tolerated, and overall, the safety profile between treatment groups in the study at the time of analysis was generally comparable, which is encouraging. We are in the process of engaging with regulatory agents to discuss potential accelerated approval submissions for FSGF. As such, we will not be in a position to provide a regulatory update today but remain on track to do so as planned before the end of the first half of the year.

We also continue to see additional trial level analysis published in this space specifically in Iga nephropathy that clearly link the benefit of proteinuria reduction with beneficial outcomes and Egfr.

Importantly, these are consistent with how we have designed our protect study and we're looking forward to those results coming up soon.

We also continue to be excited about pegged to bad news the new non proprietary name for our CVP 058 molecule in development for classical home assistant urea or <unk>.

There are no approved treatments, specifically address the underlying genetic cause of HCA the.

Eric Dube: In parallel, our protective study of sparsensin in IJ nephropathy continues to advance and is nearing completion of enrollment. The study continues to receive broad support from the nephrology community and from patients and their families. Importantly, we remain on track for a top-line readout from the interim protenurea assessment in the third quarter of this year, and as we look forward to the data from Protect, we remain encouraged by the consistency with which Sparsenton has demonstrated its ability to meaningfully reduce proteinuria throughout its development.

The literature suggest that without control of HBU, approximately 25% of patients by $8 16 at 50% of patients by age 29 have thromboembolism, which can lead to heart attack and stroke avail.

Available treatments are often inadequate and patients also faced challenges with compliance and adhering to a difficult low protein diet, especially as they age. So we believe that there is a meaningful opportunity to help the more than 7000 patients estimated to be living with classical acu in the U S and Europe.

And in need of an effective treatment option.

Our team is working with investigators and patients to advance the ongoing phase <unk> study and.

And we continue to be encouraged by the potential to ultimately make takes about base. The first disease modifying therapy for classical home assistant urea.

We look forward to providing additional updates on the program later this year.

Our leadership position in the rare disease community is also built upon our ability to consistently deliver our approved therapies to patients.

Eric Dube: We also continue to see additional trial-level analyses published in the space, specifically in IG nephropathy, that clearly link the benefit of proteinuria reduction with beneficial outcomes in EGFR. Importantly, these are consistent with how we have designed our Protect study, and we are looking forward to those results coming up soon. We also continue to be excited about Peg Tabatinase, the new non-proprietary name for our TBT-058 molecule in development for classical homocystinuria or HCU.

In the first quarter, we experienced some challenges in new patient referrals from the ongoing pandemic, but our commercial organization continued to deliver and the underlying strength of our business remains.

Importantly, we have maintained consistent access and support for our approved treatments through the challenges over the last year.

And while we had a slower than anticipated months for new patient starts in January and February as a result of the resurgence of COVID-19 in the fall, we did see new patient referrals meaningfully increase in March and through April <unk>.

This provides us with the confidence that we can achieve our full year guidance of mid single digit growth and ultimately drop on our expertise and resilience to be successful in delivering smart sensing if approved.

Let me now turn the call over to Noah for updates from the pipeline no.

Thank you art and good afternoon, everyone.

We continue to be encouraged by our our engagement with the neurology community as we work towards the goal of developing <unk> as a new treatment standard for US, yes, and Iga nephropathy if approved.

Eric Dube: There are no approved treatments that specifically address the underlying genetic cause of HCU. However, the literature suggests that without control of H-DU, approximately 25% of patients by age 29, and 50% of patients by age 29 have thrombo embolism, which can lead to heart attack and stroke.

Eric referenced earlier, there was a clear recognition that <unk> is a leading cause than 16 disease and subsequent kidney failure. Unfortunately, the incidence and prevalence of <unk> is believed to be on the rise as there are no approved medicines indicated for this disorder.

As a result patients living with <unk>, often require aggressive treatment options, such as immune suppressive therapy dialysis and transplantation.

Eric Dube: Available treatments are often inadequate, and patients also face challenges with compliance and adjusting to a difficult, low-protein diet, especially as they age. So we believe that there is a meaningful opportunity to help the more than 7,000 patients estimated to be living with classical HCU in the US and Europe and in need of an effective treatment. Our team is working with investigators and patients to advance the ongoing phase one-two study, and we continue to be encouraged by the potential to ultimately make Peg Tabatinase the first disease-modifying therapy for classical home-assisted urea. We look forward to providing additional updates on the program later this year.

Even if these treatments are successful they called the challenges for people to go about daily living.

This significant unmet need provides us with a sense of urgency each day as we continue to advance our program.

Following the announcement of the interim results from the ongoing pivotal duplex study of store sensitive assets, yes. Our medical team has continued to receive broad support from the nephrology and advocacy communities. As we previously mentioned sustained progress on reduction is recognized as a primary preclinical amongst the fall just managing.

Yes.

This is driven by the well accepted length among nephrology community about lowering total area results in improved kidney outcomes. In this population we are at the forefront of development with the first pivotal study demonstrating a meaningful reduction of proteinuria compared to currently available treatments if approved we believe.

Eric Dube: Our leadership position in the rare disease community is also built upon our ability to consistently deliver our approved therapies to patients. In the first quarter, we experienced some challenges in new patient referrals from the ongoing pandemic, but our commercial organization continued to deliver, and the underlying strength of our business remains. Importantly, we have maintained consistent access and support for our approved treatments through the challenges over the last year. And while we had slower than anticipated months for new patient starts in January and February as the result of the resurgence of COVID in the fall, we did see new patient referrals meaningfully increase in March and through April.

Thanks for sneaking it can become an important new treatment option that physicians can use as the base of their treatment paradigm.

Eric outlined earlier.

We're in the process of discussing our plans to pursue accelerated approval submissions for <unk> with regulators and we continue to expect that we'll be in a position to provide an update on a regulatory pathway before the end of the first half of the year as planned.

While we reached an important milestone with the duplex study achieving its interim primary endpoint, we still need to complete the confirmatory phase of the study.

Our blinded duplex team continues to engage sites and investigators to ensure patient retention and maintain high quality trucks on the up throughout the two year Egfr endpoint of the study.

Eric Dube: This provides us with the confidence that we can achieve our full year guidance of mid-single-digit growth and ultimately draw upon our expertise and resilience to be successful in delivering sparsentine if approved. Let me now turn the call over to NOAA for updates from the pipeline. Thank you, Art.

I am very pleased with the progress on study, thus far and we remain on track for topline data.

Noah Rosenberg: And good afternoon, everyone. We continue to be encouraged by our engagement with the nymphology community as we work towards the goal of developing Spursenten as a new treatment standard for FSCS and hygiene apopathy, if approved. As Eric referenced earlier, there is a clear recognition that FSDS is a leading cause of NSQKin disease and subsequent kidney failure. Unfortunately, the incidence and prevalence of FSGS are believed to be on the rise, and there are no approved medicines.

From the confirmatory endpoint in the first half of 2023.

Following the interim results from duplex enthusiasm amongst key opinion leaders continues for the upcoming readout of the phase III protect study of <unk> in Iga nephropathy.

Once I got this yes.

The property is also a leading cause of end stage kidney disease, notably is estimated to affect between 250 and 350000 people in the U S and Europe volume.

Similar to <unk> inflammation fibrosis, and proteinuria play key roles in Iga nephropathy.

<unk> simultaneously on selectively blocks the endothelin.

Noah Rosenberg: indicated for this disorder. As a result, patients living with FSGS often require aggressive treatment, such as immune suppressant therapy, dialysis, and or transplantation. Even if these treatments are successful, they come with challenges for people to go about daily living. This significant unmet need provides us with a sense of urgency each day as we continue to advance our programs.

Angiotensin receptors the areas believed to be responsible for the inflammation fibrosis, and proteinuria and Iga Nephropathy importantly, preclinical models <unk> has consistently shown the ability to prevent from a low sclerosis, and residual cell proliferation, and reduce coronary and Iga nephropathy.

And the importance of proteinuria as a treatment target and its correlation to Egfr continues to strengthen in Iga nephropathy as well.

Again, it is a low stablish at the higher preliminary up one has a baseline is generally translates to a SaaS progression of disease and that reducing proteinuria is associated with improved outcomes. A recent publication from Dr. Incur at Tufts University amongst others further strength no link between currently.

Noah Rosenberg: Following the announcement of the interim results from the ongoing pivotal duplex study of Spursanthen and FSGS, our medical team has continued to receive broad support from the nephology and advocacy communities. As we previously mentioned, sustained prognary reduction is recognized as the primary treatment goal amongst nephologists managing FSGS, which is driven by the well-accepted link among the morphology community that lowering prognaria results We are at the forefront of development with the first pivotal study demonstrating a meaningful reduction in protein area compared to currently available treatments.

Reductions in proteinuria and effects on Egfr slope in Iga nephropathy.

Alex This evaluated 12 studies of multiple interventions and found the treatment effects on proteinuria accurately predicted treatment effects on egfr slope, specifically the publication cited that an observed treatment effect of approximately 30% reduction in proteinuria with confirmed at least 90% probability.

For treatment benefit and slope of Egfr at two years. These findings are consistent with the design of our protect study.

Protect is also similar in many ways. The duplex study, but there are some notable differences between the two.

Noah Rosenberg: If approved, we believe that Spursenk can become an important new treatment option that physicians can use as the base of their treatment paradigm. As Eric outlines earlier, we are in the process of discussing our plans to pursue accelerated approval submissions for FHS with regulators.

Protect enrolls patients with one brand per gram or more of proteinuria per day compared to duplex, which included those with one five or more while one gram per gram in IGT property is progressive in nature. These volumes are reflective of the fact that <unk> tends to be a more heavily partner disease.

Noah Rosenberg: And we continue to expect that we'll be in a position to provide an update on our regulatory pathway before the end of the first half of the year, as planned. While we reached an important milestone with a duplex study, achieving its interim partner endpoint, we still need to complete the confirmatory phase of the study. Our blinded duplex team continues to engage sites and investigators to ensure patient retention and maintain high quality trial conduct throughout the two-year EGFR endpoint of the study.

All patients are coming into the protect study on Max dose <unk> therapy, and there is no washout period prior to randomization and.

And finally at the interim analysis with duplex, we measured <unk>, which is a combined endpoint that requires the patients meet both a threshold of greater than 40% reduction of proteinuria from baseline and to get below one five grams per gram of proteinuria per day protect is designed with an interim assessment of relative.

Per cent reduction of proteinuria. After 36 weeks of treatment. The study is powered to show a 30% relative reduction in proteinuria from <unk> versus Irbesartan.

Noah Rosenberg: I am very pleased with the progress of the study thus far, and we remain on track for Topline Data from the confirmatory endpoint in the first half of 2023. Following the interim results from Duplex, enthusiasm amongst key opinion leaders continues for the upcoming readout of the Phase 3 Protect Study of Spercentan in IGA Ophopathy. Much like FS, hygieneopathy is also a leading cause of NCHQ disease. Notably, it is estimated to affect between 250,000 and 350,000 people in the U.S. and Europe combined. Similar to FHGS, inflammation, fibrosis, and proteinuria play key roles in IGA nephropropathy. Sprentine simultaneously and selectively blocks the endothelin and angiotensin receptors.

A treatment effect of 30% will be expected to confer a benefit on egfr compared to irbesartan over two years consistent with the comprehensive publication from Tri level analyses.

Unit profitability of note. We are on track to report topline data from the interim preliminary analysis in the third quarter of this year.

Enrollment in protect remains strong we recently closed screening in the study and anticipate randomize them the last patient in the near future also.

Elsewhere in the pipeline, we have successfully completed the integration of the <unk> program for HCA.

As Eric outlined earlier this is the newly assigned non proprietary name for our TVT five to eight molecule that we acquired late last year, our optimism to potentially develop and deliver the first potential disease modifying therapy for HBU continues to grow as we spend more.

With the program.

We have been fortunate to engage directly with the HCM community and investigators and we look forward to integrating their insights to optimize the program as we move forward.

Noah Rosenberg: The area is believed to be responsible for the inflammation, fibrosis, and proteinuria and IJ nephropathy. Importantly, preclinical models of sporescentant have consistently shown the ability to prevent remandial cell proliferation and reduced protinuria in IGA nephropathy. And the importance of prognuria as a treatment target and its correlation to EGFR continues to strengthen in IGA nephropathy as well. In Igan, it is a role established that the higher the protenuria, the higher the baseline. This generally translates to a fast regression of disease, and that reducing protenuria is associated with improved outcomes. A recent publication from Dr. Inker at Tufts University, amongst others, further strengthens the link between early reductions in protenuria and effects on EGFR slope and Igenopropathy.

<unk> dose escalation study to assess the safety Tolerability pharmacokinetics, pharmacodynamics and clinical effects of pegged to batteries continues to advance we have worked through some COVID-19 related challenges with the types of batteries program such as opening new sites, but we now have one site to enrolment of the final patient.

And the highest cohort for this.

Currently plan, assuming we remain on schedule. We will expect this will provide us with an initial look on how dosing and safety are progressing in this study later this year. This should provide us with the ability to determine if we have identified the optimal dose cohort or if the program could benefit from additional cohort in parallel we continue.

To advance the ongoing natural history study.

We expect this to be instrumental in gaining a deeper understanding of the progression of acu and to establishing the regulatory pathway.

For the clinical program.

We anticipate beginning our dialogue with regulators for HQ later, this year and look forward to providing additional insights as they become available.

Overall I continue to be very pleased with our clinical efforts and our progress in pursuing our mission of identifying developing and delivering life changing therapies to people with rare disease.

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

Noah Rosenberg: The analysis evaluated 12 studies of multiple interventions and found the treatment effects on protanuria accurately predicted treatment effects on EJFR slow. Specifically, the publication cited that an observed treatment effect of approximately 30% reduction in proteinuria would confer at least 90% probability of treatment benefit on the slope of EGFR at two years. These findings are consistent with the design of our Protect study. Protect is also similar in many ways to the Duplex study, but there are some notable differences between the two.

Thank you Paula.

Our team has begun begin with great motivation to deliver our approved therapies and to prepare for potential future far simple launches.

The commercial organization has performed well through a challenging period and have provided a solid foundation for us to build upon throughout 2021.

During the first quarter, we saw new patients initiate therapy for all three of our approved products.

However, COVID-19 related dynamics resulted in a slight year over year net product sales performance.

And the onset of the pandemic in the first quarter of last year, we experienced increased demand from patients to have product on hand.

This resulted in a revenue above expectations of approximately one $5 million to $2 million in the first quarter of last year.

Noah Rosenberg: Protecting roles patients with one gram or more of proteinuria per day, compared to duplex, which included those with 1.5 or more. While one grant program in Igenopathy is progressive in nature, these values are reflective of the fact that FSGS tends to be a more heavily protinic disease.

As expected.

This did not recur in the start of this year.

And the other important dynamic is accumulative effect net.

COVID-19 has had some patients visiting their physicians.

Surprisingly when COVID-19 case accelerators in the fall and in the beginning of 2021, we did see fewer patient referrals from our approved products.

This industry wide strength has had.

From impacts from our January and February months, and created a modestly slower than expected starts to the year.

Noah Rosenberg: All patients are coming into the Protect Study on max dose ACE Arb therapy, and there is no washup period prior to randomization. And finally, at the interim analysis with Duplex, we measured FPRE, which is a combined endpoint that requires the patients meet both a threshold of greater than 40% reduction in protein area from baseline and to get below 1.5 grams of protein per day. Protect is designed with an interim assessment of the relative percent reduction of proteinuria after 36 weeks of treatment. The study is powered to show a 30% relative reduction in proteinuria for sparseantan. versus Herbicart.

Net debt in March we started to see stronger new patient referrals in the first two months of the year and we are seeing that momentum now continues through April. So we are encouraged by its underlying strength that expressions.

Also during the quarter, we experienced a higher gross to net sector driven primarily by the insurance resets in the beginning of year on year.

Is this expected on our business and consistent with previous years, and we anticipate to return to our normal levels on the remainder of the year.

Taking all of this into account we believe we are in solid position to identify and treat patients through the balance of the year.

As Eric mentioned before we continue to expect mid single digit growth for our approved products in 2021.

We are also continuing our work to prepare for launches in FCS can Iga nephropathy is far symphony ultimately approves.

Noah Rosenberg: A treatment effect of 30% will be expected to confer a benefit on EGFR compared to Erbosart in over two years, consistent with the comprehensive publications from tri-level analyses in Igenapropathy to date. Of note, we are on track to report top-line data from the Interimportner Analysis in the third quarter of this year. Enrollment in Protect remains strong. We recently closed screening in a study and anticipate randomizing the last patient in the near. Elsewhere in the pipeline, we have successfully completed the integration of the Peg to Batanese program for HCU.

We continue to strengthen our understanding of the patient journey and what it will take to provide broad access to therapy.

We are continuing to do the foundational work to put the pieces in place to launch the product in a space that has seen limited innovation over the last few decades.

We have confidence.

Our established commercial infrastructure <unk>.

Our rare disease expertise and our ongoing insight generation and launch planning preparations will ultimately enable us to be successful in delivering plus income to people, making this ethic es NIH in Iga nephropathy.

Groups.

I'd like to turn the call over to more on now for the financial update.

Laura.

Thank you Peter.

For the first quarter of 2021, we reported net product sales of $47 4 million from our commercial portfolio, which was comparable to the same period in 2020.

We reported a GAAP net loss of $53 9 million for the first quarter of 2021.

Noah Rosenberg: As Eric outlined earlier, this is the newly assigned non-procpiratory name for our TBT 058 molecule that we acquired late last year. Our optimism about potentially developing and delivering the first potential disease-modifying therapy for HCU continues to grow as we spend more time with the program. We have been fortunate to engage directly with the HCU community and investigators, and we look forward to integrating their insights to optimize the program as we move forward.

After adjusting for non cash expenses and income tax we reported a non-GAAP net loss of $31 2 million for the first quarter of 2021.

On a GAAP basis, R&D expenses were $47 9 million for the first quarter of 2021.

The increase compared to 2020 is largely attributable to increased pace of patient enrollment in the ongoing pivotal duplex and protect studies start scanning as well as the integration and advancement of the take of that make programming classical HCM.

Noah Rosenberg: The Phase 1 through dose exploration study to assess safety tolerance

On an adjusted basis R&D expenses were $44 7 million for the first quarter of 2021.

Noah Rosenberg: to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and clinical effects of Peg to Batanese continue to advance. We have worked through some COVID-related challenges with the Peg to Batanese program, such as opening new sites, but we now have a line of site to enrollment of the final patient in the highest cohort that is currently planned. Assuming we remain on schedule, we will expect them to provide us with an initial look at how dosing and safety are progressing in this study later this year.

Relevant non cash expenses for the first quarter included $3 3 million net stock based compensation and amortization.

On a GAAP basis, selling general and administrative expenses for the first quarter were $36 8 million.

The increase over the same period in 2020 is largely attributable to increased compensation expense to support the growth of our organization and initial investment in launch preparation activities.

On an adjusted basis SG&A expenses for the first quarter were $26 3 million.

Significant noncash adjustments for the quarter consisted of $10 5 million in stock based compensation and depreciation and amortization.

Peter Heerma: This should provide us with the ability to determine if we have identified the optimal dose cohort or if the program could benefit from an additional cohort. In parallel, we continue to advance the ongoing natural history study. We expect this to be instrumental in gaining a deeper understanding of the progression of HCU and to establishing the regulatory pathway for the clinical program. We anticipate beginning our dialogue with regulators for HCU later this year and look forward to providing additional insights as they become available.

Looking ahead, we expect our operating expenses to increase modestly from Q1 levels.

This may be uneven quarter to quarter, but is expected to occur occur throughout the balance of the year as we continue to support the ongoing pivotal duplex and protect studies that are setting, which will advance our plans to their respective confirmatory two year endpoint.

It also accounts for investing in the success of the take to that makes program in classical HP year, and preparing our organization for potential commercial launch it.

Our financial Foundation is the purchase activity remains strong.

We ended the first quarter with $529 million in cash and cash equivalents.

Peter Heerma: Overall, I continue to be very pleased with our clinical efforts and our progress in pursuing our mission of identifying, developing, and delivering life-changing therapies to people with rare diseases. I'll now turn the call over to Peter for the commercial update.

Notwithstanding additional business development.

Total cash balance is expected to support our current operations beyond the next two years.

I will now hand, the call back over to Eric for his closing comment Eric.

Thank you Laura execution remains a core strength for our organization and I would like to thank all of our team members and partners for their continued commitment to our mission. We have started off the year well. Our performance is in large part driven by the sense of urgency that is created by listening to patients perspective, and the clear need for new <unk>.

Peter Heerma: Our team has begun the year with great motivation to deliver our approach therapies and to prepare for the potential futures for Sparcenton launch. The commercial organization has performed well through a challenging period and provided a solid foundation for us to build upon throughout 2021. During the first quarter, we saw new patients initiate therapy for all three of our approved products. However, COVID-19-related dynamics resulted in a flat year-over-year net product sales performance.

Treatment options.

Channel. This as we continue our work with leaders in the rare nephrology community to break new ground in the pursuit of bringing the first innovation in decades to people living with <unk> and Iga nephropathy and it will continue to drive our efforts to further develop and deliver the potential first disease modifying therapy for classical HCM.

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

Alright, Thanks, Eric Brandon can we please go ahead and open up the line for Q&A.

Yes. Thank you Sir we will now begin the question and answer session. If you have a question. Please press star one on your phone.

Pat.

You'd like to be removed from the queue. Please press the pound side or the hash key.

It has shown a speaker phone please pickup your handset first before tightly once.

Peter Heerma: At the outset of the pandemic in the first quarter of last year, we experienced increased demands from patients to have products on hand. This resulted in revenue above expectations of approximately $1.5 to $2 million in the first quarter of last year. As expected, this did not recur at the start of Dish.

Again, if you have a question. Please press star one on your phone keypad.

And from SBB Leerink, we have Joseph Schwartz. Please go ahead.

Alright, thanks, so much for all the insightful commentary for <unk>.

Taking my questions I.

I guess my first one is just.

You referenced a lot of the continuing.

In literature that supports the use of.

You are.

Analysis that you'll be doing in protect and Iga nephropathy and I know you worked really hard to hammer out.

Peter Heerma: An other important dynamic is the cumulative effect that COVID-19 has had on patients visiting their physicians. Unsurprisingly, when COVID-19 cases accelerated in the fall and at the beginning of 2021, we did see fewer patient referrals for our approved product. This industry-wide trend has had an impact on our January and February demands and created a modestly slower than expected start to the year. That said, in March, we started to see stronger new patient referrals than in the first two months, and we have seen that momentum now continues for April.

A variation on that.

GFS years ago with the FDA. So im just wondering just given it seems like there is a continuous string of surprises from the agency.

Due to various reasons such as personnel shifts or maybe the same April looking at things differently now than years ago.

And some on known reasons granted.

I'm wondering if.

If you could just characterize for us how.

How much commonality is there between like the personnel that you're dealing with now.

And how they might look at things versus when you establish the analysis plan.

<unk>. Thanks.

Thanks for hearing my long question.

Thanks, Joe Barry.

Very clear question and I'll have a few comments and then I'll ask bill to.

To provide further information so I would say that overall as we look at our programs. How they were designed years ago, and where we are today in a very innovative trial design looking at proteinuria at 36 weeks.

Peter Heerma: So we are encouraged by the underlying strings, that is, Also, during the quarter, we experienced a higher gross-to-net factor driven primarily by the insurance resets in the beginning of the new year. This is expected in our business, inconsistent with previous years, and we anticipate this to return to our normal levels for the remainder of the year, taking all of this into account.

<unk> the longer term over two years.

Literature to support that link is only growth and as you mentioned certainly.

So for Iga nephropathy with some of the recent analyses and I think that FDA certainly recognizes that I don't want to speak for any regulators, but we believe they understand.

On top of the literature.

To provide further comments on on.

Peter Heerma: We believe we are in a sound position to identify and treat new patients through the balance of the year. As Eric mentioned before, we continue to expect mid-single-digit growth for our approved products in 2021. We are also continuing our work to prepare for launches in FS and IGA and property. If Sparsent, then it's ultimately approved. We continue to strengthen our understanding of the patient journey and what it will take to provide broad access to therapy.

How things have evolved with the agency from your perspective.

Certainly.

And thanks for the question Joe.

I've been on these projects for almost four and a half years and the group across the table from us and cardio renal has been relatively quite consistent there's been very little change in turnover.

We've seen some members of the team.

B second into other areas of the agency for COVID-19 specific tasks and then return after a period of six to nine months.

And the agency in that period.

<unk> the way they allocated statistical.

Peter Heerma: We are continuing to do the foundational work to put the pieces in place to launch a product in a space that has limited innovation over the last few decades. We are confident that our established commercial infrastructure, our rare disease expertise, and our ongoing insight generation and long-spending preparations will ultimately enable us to be successful in delivering sparsencome to people living with FS and hygiene neuropathy if approved.

Professionals and that resulted in a change in some of the people on the team.

From the <unk>.

Medical and leadership positions within the <unk> Division.

Division, we've been dealing with pretty much the same people the whole way through.

Great.

Very helpful. Thanks for the color.

And then you mentioned Russia.

Laura I think was mentioned.

Starting to build out.

Enhanced commercialization capabilities on top of what you already have.

Can you just.

Laura Kathryn Chico: For the first quarter of 2021, we reported net product sales of 47.4 million from our commercial portfolio, which was comparable to the same period in 2020. We reported a gap net loss of $53.9 million for the first quarter of 2021. After adjusting for non-cash expenses and income tax, we reported a non-gap net loss of $31.2 million for the first quarter of 2021. On a gap basis, R&D expenses were $47.9 million for the first quarter of 2021.

Parameter is that for us both in the U S debt at what point do you think it might make sense to build outside the U S. If ever given you don't currently have much of a presence there, but this could be a global brand.

Service margin and our thanks, Joe our plan certainly for <unk> is to commercialize in both the U S and Europe.

The approach that we've taken Europe.

Still.

Under review, whether we do that our own or whether we partner, but I'll ask Peter to talk a little bit about the activities that this team is undertaking to prepare for commercialization.

Yes, thanks, Eric so to start with.

Part of the question with regards to Europe.

So we think unmet needs in euro is equally high.

On the U S.

But the dynamics in Europe are quite quite different. So we are really focusing right. Now is can we get a good understanding of the addressable patient population as well as what would be.

Laura Kathryn Chico: The increase compared to 2020 is largely attributable to increased patient enrollment in the ongoing pivotal duplex and protect studies of Spars Sentence, as well as the integration and advancement of the Peg to Batonase program in classical HCU.

Those of disease, and what does it take what is the requirement to gain access to phases.

And we're making disciplined investments right now on him.

We are quite pleased with the progress and as Eric said, we havent made them.

Statements on this evening.

<unk> utilized on the shelves.

Laura Kathryn Chico: On an adjusted basis, R&D expenses were $44.7 million for the first quarter of 2021. Relevant non-cash expenses for the first quarter included 3.3 million of stock-based compensation and amortization. On a gap basis, selling general and administrative expenses for the first quarter were 36.8 million. The increase over the same period in 2020 is largely due to

With regards to the first part of your question what are we doing from a commercialization perspective, well last year.

David is a little bit of display of debt during our R&D day.

And that's mainly an insight generation patient journey addressable patient population.

<unk> framework.

And this year, we are continuing debt.

Looking also on for size and second patients.

Ultimately sign on but what would be the field force require.

We also look at the distribution model.

The best way to bring the product to patients as well.

Laura Kathryn Chico: attributable to an increase in compensation expense to support the growth of our organization

Laura Kathryn Chico: and initial investment in launch preparation activities.

Laura Kathryn Chico: On an adjusted basis, SG&A expenses for the first quarter were $26.3 million. Significant non-cash adjustments for the quarter consisted of 10.5 million in stock-based compensation.

Laura Kathryn Chico: compensation and depreciation and amortization. Looking ahead, we expect our operating expenses to increase modestly from the Q1 level. This may be uneven quarter to quarter but is expected to occur throughout the balance of the year as we continue to support the ongoing pivotal duplex and protect studies of sparsent, which will advance as planned to their respective confirmatory two-year endpoints. It also accounts for investing in the success of the Peg to Batonase program in Classical HCU and preparing our organization for potential commercial launches.

Alright study integrity, we've got the ongoing to your confirmed free endpoint and you'll be recognized desire to see the full data, but we have no plans right now to publish further we continue to evaluate central opportunity that wouldn't introduce bias and the acceptable to regular.

Laura Kathryn Chico: Our financial foundation to support this activity remains strong.

Laura Kathryn Chico: We ended the first quarter with $520.9 million in cash and cash equivalents. Notwithstanding additional business development, this total cash balance is expected to support our current operations for the next two years.

<unk>.

We'll update you as we as we get there.

Yep. Thank you know the only thing that I would say Greg. In addition is that we have at the approach that we're taking with with duplex to do exactly what Noah said, which is to maintain the study conduct through to the end and to maintain the study blind which is of the utmost importance.

To us.

Want to share a little bit about how we're doing that.

And making sure that as we think about additional data there is no plan for any additional on blinding at this point and so there was a very small team that is working on those data to support the regulatory filings.

Laura Kathryn Chico: I will now hand the call back over to Eric for his closing comments.

Eric Dube: Thank you, Laura. Execution remains a core strength for our organization, and I would like to thank all of our team members and partners for their continued commitment to our mission. We have started off the year well.

But beyond that there was nothing else that we have planned until we complete the study.

Got it that makes sense and then one other one I know this on is also maybe a little early but.

And if you can't give specifics maybe we can just talk about the factors you'd consider but I wanted to get your latest thinking foreigners sparse sentence pricing.

Eric Dube: Our performance is in large part driven by the sense of urgency that is created by listening to patients' perspectives and the clear need for new treatment options. We will channel this as we continue our work with leaders in the rare nephrology community to break new ground in the pursuit of bringing the first innovation in decades to people living with FSGS and IJ nephropathy. And it will continue to drive our efforts to further develop and deliver the potential first disease-modifying therapy for classical HCU. Let me now turn the call over to Chris for Q&A. Chris?

And just how you're thinking about balancing.

Pricing and for the volume provided to the patients vs.

Providing broad access, especially.

I know you've you've talked about.

That day that it will likely be used eventually in combination.

With other treatments as a little.

Okay is there a true so I just wanted to get your thoughts on there.

Sure. So I think it is too early for us to talk specifically about pricing, but what I can say is that our goal is to make sure that we have brought access to this innovation. So many patients have been waiting and we want to make sure that.

That does not become a barrier for.

For for these patients and.

Christopher Cline: Great, thanks, Eric. Brandon, can we please go ahead and open up the line for Q&A? Yes, thank you, sir.

That includes the potential to combined with other therapies and we know that that may be a concern prepares but I can say that Peter and his team are very much focused on making sure. It's as you mentioned earlier on the value framework for for access Peter anything else that you would want to add.

Brandon: We'll now begin the question and answer session. If you have a question, please press star 1 on your phone keypad. If you'd like to be removed from the queue, please press the pound sign or the hash key. If you're on a speaker phone, please pick up your handset first before dialing.

But I think you mentioned I think.

Take a step back and say like you should think about and Thanksgiving <unk>.

Hi, This is about one of 25000 based on you.

And the costs associated with that is about 60 building. So these patients are among the most expensive patient on society and if you look then at <unk>.

Brandon: Once again, if you have a question, please press star 1 on your phone keypad. And from SVB Lyrink, we have Joseph Schwartz. Please go ahead.

Probably.

From a fan.

Progression and they are disproportionately representative in debt.

Patient population.

I think there is a good day as in that respect for to come up with like solids.

Joseph Patrick Schwartz: Hi, thanks so much for all the insightful commentary and for taking my questions. I guess my first one is just, you know, you referenced a lot of the continuing literature that supports the use of your analysis that you'll be doing in Protect and IJ Nepropathy. And I know you worked really hard to hammer out a variation on that in FSGS years ago with the FDA. So I'm just wondering, just give it.

No you've proposition net and we're doing right now.

Great Super helpful. Thanks for taking my question.

Thanks, Greg.

From Barclays. We have Carter gold. Please go ahead.

Yes, Hi. This is just an on for Carter, thanks for taking our questions and congrats on on the progress.

Just a couple of from us on.

Can you remind us of the date on the decision making process.

Inform the selection of the 400 milligram dose sort of what gives you confidence that that's the level that will be sufficient to drive it benefit and then.

Just to confirm given out quickly and enrolled should we still expect the interim free to be around 280 patients. So it could possibly exceed that number.

Joseph Patrick Schwartz: You know, it seems like there's a continuous string of surprises from the agency due to, you know, various reasons such as, you know, personnel shifts or maybe the same people looking at things differently now than years ago. Some unknown reasons, granted. I'm wondering if, you know, if you could just characterize for us how much commonality there is between, like, the personnel that you're dealing with now and how they might look at things versus when you established the analysis plan in FSGS. Thanks for hearing my long question. Thanks, Joe.

Just and thanks for the questions and I'll answer the second one and that is the planned analysis is when the 288 patient.

The 36 week visit and because we've got complete rollman, it'll be plus or minus 280, depending on what enrollment was at that time and as I mentioned, we're on track to be able to provide that.

Analysis in the third quarter of this year and I'll turn it over to bill to talk about.

And protect.

Thanks for the question Justin.

We believe that the data from duet.

Show US and also now from duplex that 800 milligrams is the right dose for the F. S. G S population.

As you recall, both 408 hundred milligrams were used in the duet study and they had largely overlapping results.

Eric Dube: Very clear question, and I'll have a few comments, and then I'll ask Bill to provide further information. So I'd say that, you know, overall, as we look at our programs, how they were designed years ago and where we are today in a very innovative trial design looking at proteinurate for 36 weeks and EGFR, you know, longer term over two years, the literature to support that link has only grown. And as you mentioned, certainly so for IJ nephropathy with some of the recent analyses.

When we looked at the P. K P. D. Kurds, we also saw a high degree of overlap.

Essentially the 400 and the 800 or both at the top of a sigmoidal dose response curve. So while you have on a larger numeric difference between the two the effective difference isn't.

Ah doubling between 400 800.

Specifically to Iga nephropathy and F. S. G. As they are different diseases, and they present differently starting with with.

Eric Dube: And I think that FDA certainly recognizes that I don't want to speak for any regulators, but we believe they understand and are on top of the literature. Bill, do you want to provide further comments on, you know, how things have evolved with the agency from your perspective? Certainly, and thanks for the question, Joe. I've been on these projects for almost four and a half years, and the group across the table from us at Cardio Renal has been relatively quite consistent.

<unk> <unk>, it's a highly protein uric disease and has a high degree of nephrotic Croton area with that comes a loss of albumin. Another plasma proteins and sports center is highly protein bound in circulation. So when you lose protein you also losing <unk>.

800 milligram dose and <unk> patients is designed to compensate for that potential loss.

Contrast, net to Iga nephropathy patients, we're putting areas lower the rate of nephrotic from your area is much less and so we don't see the need to have a higher dose there to compensate for that event.

Eric Dube: There's been very little change in turnover. We've seen some members of the team be seconded to other areas of the agency for COVID-specific tasks and then return after a period of six to nine months. And the agency, in that period, shuffled the way they allocated statistical professionals, and that resulted in a change in some of the people on the team. But from the medical and leadership positions within the review division, we've been dealing with pretty much the same people the whole way. Great, that's super helpful. Thanks for the color.

That along with our modeling and that the.

Where those two doses fall on the signal adult dose response curve gave us confidence that 400 at the right dose for the Iga nephropathy patients.

Awesome. Thank you so much for the color of their.

Sure.

From Jeffries, we have Marie Raycroft. Please go ahead.

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

I know you mentioned, you're not providing a regulatory update by time wondering if you can clarify if you had an initial free NDA meeting and you're not on the back and forth dialogue or is the ongoing engagement related to preparation ahead of a formal meeting scheduled for QQ.

And then as follow up can you comment on potential scenarios for outcomes from the regulatory engagement.

Eric Dube: And then you mentioned, actually Laura, I think, was the one that mentioned starting to build out, you know, enhanced commercialization capabilities on top of what you already have. Can you just, parameterize that for us both in the U.S. and, at what point do you think that it might make sense to build outside the U.S., if ever given you don't currently have much of a presence there, but this could be a global brand?

More thanks, so much for your questions and.

Typical practice is that we don't provide specific date for a regulatory interactions.

We have guided to previously we are in the process of engaging with both GMA and FDA and we're on track to be able to provide an update on those interactions by the end of this quarter and with regard to your second question around scenarios I would say, it's probably we're not in a position to be able to speculate where that might.

We'll be able to provide updates on on those.

Our actions in and.

Eric Dube: Certainly, and you know, our plan for Sparsenton is to commercialize it in both the U.S. and Europe. And, you know, the approach that we take in Europe is still under review, whether we do that on our own or whether we partner. But I'll ask Peter to talk a little bit about the activities that this team is undertaking to prepare for commercialization.

Any implications on our business later this quarter.

Fair enough.

Okay, and then maybe one other question just on.

Again.

And protect.

You mentioned as close to fully enrolled can you comment on base baseline proteinuria range or anything else on baseline characteristics and whether it's in line with expectations.

And if you can remind me if you expect greater approach in your ear improvement innovations with higher protein you react baseline or how do you think about that.

On.

Sure no or would you like to take balance.

Peter Heerma: Yeah, thanks, Eric. So to start with the most important part, the question we've got to Europe. So we think that the level in Europe is equally high as in the U.S., but the dynamics in Europe are quite different. So what we are really focusing right now is to get a good understanding of the addressable patient population in Europe, as well as what the burden of disease is, and what does it take, what is the requirement, to gain broad action?

Sure.

Great Alright, so as far as the approach that we take keeping in mind that protects study is currently blind debt. So any analyses were doing really both groups together are blinded analyses.

All of the data for quality go through making sure that the date is.

Hi Fi quality is reflecting that is consistent with our expectations for.

For for baseline.

Factors. So I think that's as much as I can say about the based on characters has been more there was another part of your question.

Peter Heerma: And we're making the disciplined investment right now, and I think we are quite pleased with the progress. And, as Eric said, we haven't made a public statement on whether we would commercialize it. With regard to the first part of your question, what are we doing from a commercialization perspective? Last year, and we gave a little bit of a demonstration of that during our R&D day, we invested mainly in insight generation, patient journey, and rest of patient population, the value framework.

Yep, Yeah, just your expectations for patients with higher approach in your area at baseline.

You expected and have a greater magnitude of benefit more improvement.

Yeah Yeah.

And I'll just add also.

You would expect a slightly lower very.

Right.

Lower extracurricular interest first the first question right.

As far as the reduction we.

We did see a slightly let me <unk>.

From your reduction and to add a duplex above and below.

Inner product range on.

Peter Heerma: And this year we are continuing that, looking also at P.O.4 size and second patients, to ultimately say, like, what is the field force required. We also look at the distribution model and what is the best way to bring the product to patients, as well as educational initiatives, both for patients as well as for physicians, because FSDS is an underserved disease, and I think educational efforts are needed there to really gain understanding of the study that we conducted, but also F.P.R.E. is our

But it was slightly diminished and the higher group on compared to the larger so we might expect that but remember that and again, we're having a less neurotic population that we are at F. A chef so probably wouldn't have as much of an impact with me I predict but again, we will have a data back in August.

That.

Sure.

Got it okay. Thanks for taking my question.

From Evercore ISI, we have Lisa <unk>. Please go ahead.

Hi, yes.

I just want to clarify.

Is it your expectation that you're going to file an accelerated per well just to clarify.

It's just the way you phrased that I wanted to make sure that it's your expectation that you are going to file for accelerated accelerated approval based on the day that you have correct.

Greg Harrison: Thanks again for all the insights. Now, from Bank of America, we have Greg Harrison.

Hi, Lisa Yes, so accelerated approval is our base case and we're.

Greg Harrison: Please go ahead. Hey guys, thanks for taking the question. My question is on the Duplex study. Will there be an opportunity to see additional data from that study, particularly EGFR? And is this something that there could be periodic updates for or, you know, medical conference presentations planned before you were to get an accelerated approval? So Noel, why don't you take that one with regard to additional data and also any potential presentations? Yeah, that's a great question.

Currently planning the and writing the NDA for that but obviously, that's going to be subject to the ongoing interactions with regulators and that's something that we'll be able to provide update that.

Later this quarter and I think that's also why we want to make sure that we're engaging very closely with FDA. So that we understand.

Their expectations for the package and reviewing the data with them prior to submitting so that we haven't aligned approach on accelerated approval.

Okay.

Uhm and then can you maybe just review like.

Kind of.

Four separately from <unk> and for Iga nephropathy.

Noah Rosenberg: So, you know, in terms of the overall data for Duplex, as you know, we really had to and continue to provide minimal data to protect the study integrity. You know, we've got the ongoing two-year confirmatory endpoint, and, you know, we recognize the desire to see additional data, but we have no plans right now to publish it. We continue to evaluate an essential opportunity that wouldn't interest or bias and be acceptable to regulators, you know, that's, we'll update you as we get there. Thank you, No.

What kind of.

Gives you confidence that you can file on <unk> notwithstanding the data.

But using Croton area. This idea of using primary out can you maybe review kind of what what's in the public domain or what's been kind of.

Communicated with FDA that.

Lead you to believe that that you base day.

Yes, certainly on our last bill to take that one.

Certainly if we start with the public domain, there's a growing body of literature that links reductions in protein area to preservation of renal function in the long term and specifically.

Eric Dube: The only thing that I would say, Greg, in addition, is that we have the approach that we're taking with Duplex to do exactly what Noah said, which is to maintain the study conduct through to the end and to maintain the study blind, which is, you know, utmost important to us. I want to share a little bit about how we're doing that and make sure that, you know, as we think about additional data, there is no plan for any additional unblinding at this point. And so, you know, there's a very small team that is working on the data to support the regulatory filings. But beyond that, there's nothing else that we have planned until we complete the study.

Work coming out of Dr anchors lab and others.

Truth is another at Michigan and Troy on.

All are showing a consistent.

Story debt reductions in proteinuria per.

Or a slowing of the decline of renal function and all of US we have a lower GFR year by year as we age in these patients with primary on diseases that rate is faster.

If you're able to reduce the proteinuria in these patients that's expected to and has been shown to confer a reduction in egfr overtime.

I think the other element.

To to answer your question.

We've been in discussion with the agency as well as the.

Greg Harrison: Got it, that makes sense. And then one other one, I know this one's also maybe...

The EMA in Europe around trial design.

With the surrogacy.

<unk> area, and an interim endpoint being used to predict.

Greg Harrison: early but, if you can't give specifics, maybe we could just talk about the factors you'd consider but wanted to get your latest thinking as far as subsidy pricing and just how you're thinking about balancing pricing for the value provided to the patients versus providing broad access, especially as you've talked about that it will likely be used eventually in combination with other treatments and as other therapies are approved. So I just wanted to get your thoughts there. Sure.

The reductions in Egfr at the two year confirmatory on.

So the combination of both what's in the public domain and dialogue, we've had with regulators gives us confidence that this is a path that they are aligned with that could be used for accelerated approval.

And I think the other aspect leases that there is consistency in how other sponsors who obviously engaged with FDA would have designed their their programs and also per view area. So I think that consistency, while we can't speak to other programs I think is reassuring and the approach that we've received and the guidance that we've received.

Okay. Thank you.

Thankfully from.

From William Blair, We have Tim Lugo. Please go ahead.

Eric Dube: So I think, you know, it is too early for us to talk specifically about pricing, but what I can say is that our goal is to make sure that we have brought access to this innovation. So many patients have been waiting, and we want to make sure that, you know, that does not become a barrier for these patients. And, you know, that includes, you know, the potential to combine with other therapies.

Hi, guys. This is John on pretending thanks for taking a question I was just wondering if you guys could provide some commentary on how payeur discussions are going for star Santana on FTF, and maybe a bit more specifically if you could provide some color on how the payers are responding to and taking it out the interim proteinuria data. Thanks.

John Thanks for your questions and Peter would you like to take this one.

Eric Dube: And we know that that may be a concern for payers. But I can say that Peter and his team are very much focused on making sure, as you mentioned earlier, on the value framework for access. Peter, anything else that you'd want to add?

Yeah. Thank you for that question.

I think it's kind of like Bill phone conversation that the bill was just outlining how's the relationship between Baltimore way a reduction translates into a reduction of progression on <unk> and ultimately.

You may have been Thanksgiving cheese, and I think someone to work day. We have done is informs us to have those conversations on Spears Uhm you May remember D. R. D day, we'd love to better was presenting how 30% reduction in full.

Peter Heerma: But did you mention all that? I think it's good to take a step back and say, like, if you think about in-state kidney disease, it affects about 125,000 patients in the US, and the cost associated with that is about 50 billion. So these patients are among the most expensive patients for society. And if you look at them as FHDS and IGA inthropy, they're on a fast track of progression, and they are disproportionately represented in that N-SATKITNs population. I think there's a good base in that respect for coming up with this, like, a solid value proposition, and that's the work that we're doing right.

<unk> actually translate on IGN from basic level base too.

Two about over 10 years delay entries kidney disease and we're in.

Right now to do seem to look for ssds.

And I think just to kind of data on that thank you. So very interest of the issue with this game of understanding what the translation of Pulteney oriented reduction is into recently.

Heart endpoints in delay progression disease.

Alright, thanks, so much for that color.

From kindergarten Genuity, we have Michelle Gilson. Please go ahead.

Hi, This is Michael convective on permission congrats on the corner.

Greg Harrison: Great, super helpful. Thanks for taking the question. Thanks, Frank, from Barclays. We have Carter Gold. Please go ahead. Yeah, hi, this is Justin on behalf of Carter. Thanks for taking our questions and congratulations on all the progress.

One of the duplex filing and it's I got some questions about per cent and so it seems like you are engaging with regulators I guess more specifically dealing tessa paint the filing per F. S. G S. What's come before or after the interim protect data and I, then and then sort of a little more broadly do you see any read through to the FDA reached.

Carter Lewis Gould: Just a couple from us on PRICT; can you remind us of the data?

Carter Lewis Gould: decision-making process that informed the selection of the 400 milligram dose, sort of what gives you confidence that that's the dose level that will be sufficient to drive a benefit, and then Just to confirm, given how quickly and enrolled, should we still expect the interim dose to be around 280 patients? Or could it possibly exceed that number?

Really accepting other applications for rare <unk> disease to the agencies view of what the complete data package won't be for these diseases.

Michael Thanks, So much for your question and with regards to your first on on the timing of filing and whether that would occur before or after the protect interim.

Where we wouldn't be on a physician today to comment on on the sequencing of that but we are on track to provide.

Both the.

Data from protected on the third quarter and then we will provide an update on a regulatory interactive later this quarter. So so that may be something that we can provide greater detail on very soon with regard to read through of recent regulatory filings I would say a couple of things.

Noah Rosenberg: Justin, thanks for the question, and I'll answer the second one, and that is the planned analysis is when the 280th patient hits the 36-week visit. And because we've got, you know, complete enrollment, it'll be, you know, plus or minus 280 depending on what enrollment was at that time. And, you know, as I mentioned, we're on track to be able to provide that analysis in the third quarter of this year. And I'll turn it over to Bill to talk about dosing and protection. Thanks for the question, Justin.

One is that certainly there is recognition of significant unmet need very much and what I share than my prepared remarks.

With regard to rare kidney disorders, and we believe based on our interactions that regulators clearly understand this need and we are encouraged by other progress in other programs just given that it's several steps closer for patients to potentially haven't approved therapy, but each program.

I'm a different and so we can't really make comparisons between those and I certainly wouldn't want to draw conclusions any way to our programs.

Our focus is to continue the trials and to continue or.

NDA preparation and as I mentioned, we're in the process of engaging with with regulators. So we'll be able to provide an update zone.

William E. Rote: We believe that the data from Duet, uh, shows us, and also now from Duplex, that 800 milligrams is the right dose for the FSGS population. As you recall, both 400 and 800 milligrams were used in the Duet study, and they had largely overlapping results. When we looked at the PKPD curves, we also saw a high degree of overlap. Essentially, the 400 and the 800 are both at the top of a sigmoidal dose response curve. So while you have a larger numeric difference between the two, the effective difference isn't a doubling between 400 and 800.

I kind of think just switching gears just one more actually switching to TVT 058 are now newly named Pet Department. So it looks like there's a free to help a delay due to COVID-19 you mentioned an impact on opening new site is there any other way that coveted affecting the trial perhaps.

<unk>.

She has went already open paper or anything else you I haven't discussed thank you so much.

Great. Thanks for the question Bill would you like to provide your thoughts on that.

Certainly the the trial has not been free of impact from COVID-19 is as you note I think to your question of specific sites. It depends on the site and it depends on the timing there are certain times during the past 12 months.

William E. Rote: Specifically, IGA nephropathy and FSGS, they're different diseases, and they present differently. Starting with FSGS, it's a highly proteuric disease and is a high degree of nephrodic proteinuria. With that comes a loss of albumin and other plasma proteins, and sporescentin is highly protein bound in circulation.

Where some of these centers some of which are children's hospitals have not been open for.

Anybody except for specific patients.

And in that exclusion list would be somebody in a clinical trial potentially that might be on placebo. As an example, this is something that's dynamic as our lines have all been throughout the last year with COVID-19.

William E. Rote: So when you lose protein, you're also losing sparsinininin. The 800 milligram dose in FSGS patients is designed to compensate for that potential law. In contrast, to IGA nephropathy patients where protenurea is lower, the rate of nephrodic protenurea is much less, and so we don't see the need to have a higher dose there to compensate for that event. That, along with our modeling and where those two doses fall on the signaloidal dose response curve, gave us confidence that 400 is the right dose for the IGA nephropathy trait. Thank you so much for the color there.

We are seeing these restrictions ease as the <unk>.

Rates of COVID-19 have come down around the nation, but it's very individualized.

Center by Center.

And.

Two months.

We've responded to these.

By looking at the protocol and changing some of the visit schedules.

For example, using.

Nurses that go to the home to collect samples as opposed to patients having coming having to come into the hospital for a visit.

To maintain the progress of forward momentum in this study and also not to Miss.

T T samples and key data points.

Excellent. Thank you that's all for me.

Maurice Thomas Raycroft: Sure. From Jeffries, we have Marie Raycroft. Please go ahead. Hi everyone.

Thanks, Michael.

From Wedbush Securities, we have Laura Chico. Please go ahead.

Thank you very much for taking the question and I apologize. If this has already asked that I know you mentioned the anchor publication I just wanted to circle back with one on protect so one of the limitations mentioned in the inker paper was the heterogeneity of the trial data that they examined and so I was just wondering if you could talk to how you tried to it.

Maurice Thomas Raycroft: I know you mentioned you're not providing a regulatory update, but I'm wondering if you can clarify if you had an initial, in a back-and-forth dialogue, or this is an ongoing engagement. And then, as a follow-up, can you comment on potential scenarios? Maury, thanks so much for your questions. And our typical practice is that we don't provide specific dates for our regulatory interactions. But, as we've guided to previously, we are in the process of engaging with both EMA and FDA, and we are on track to be able to provide an update on those interactions by the end of this quarter.

Yes that was it protects study and also maybe your assumptions around statistical powering. Thanks.

Thank you Laura Bill I'll ask you to take this one.

Sure I think the challenge with the inker paper is.

Not unusual in the rare disease community in that there aren't a lot of clinical trials to draw from if you're doing a meta analysis and a cardiovascular space, you're gonna pull 75 studies and whittle it down through an exclusion criteria to 50 that really matter.

Maurice Thomas Raycroft: And with regard to your second question around scenarios, I would say we're not in a position to be able to speculate where that might be. We'll be able to provide updates on those interactions and, you know, any implications on our business later this quarter. Fair enough. Okay, and then maybe one other question just on IGN. You mentioned it's close to fully enrolled. Can you comment on the baseline proteinuria range or anything else on base? And if you can remind me, respect a greater approach, patients with higher, Sure. No, would you like to take that one? Sure. A great question.

In the case of the inker publication, they basically took all the the.

Treatment studies intervention on studies in Iga Nephropathy and group them together.

Taking out those that might be different for this reason or that would lead them with two small sample set. So the end result was the input was a fairly heterogeneous group I think the consistent message coming well in the result of that is they cited as one of the potential weaknesses the analysis.

But also.

It results in a greater.

Uncertainty and the measure when you start to look at the correlation and drawl regression minds.

If you look at the at the signal overall and the consistency of the message it's clear with the analyses that has been done by others as well as the work that we have done.

Noah Rosenberg: So as far as the approach that we take, keeping in mind that the protect study is currently blinded, so when the analyses we're doing, you know, we're really both groups together, far blinded analyses of the data, quality going through making sure that the data is, you know, high quality, is reflecting that it's consistent with our expectations for baseline. factors.

Terminally with registry data and other data.

On that reductions in protein area are linked to preservation of renal function.

So the day.

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I don't think that the heterogeneity cited in the anchor paper.

This is something of a concern I think it was an app.

<unk> of their input data, but I think the output message and it was really quite clear.

Noah Rosenberg: So I think that's as much as I can say about the basis for the characters. And Mori, there was another question. Yeah, just your expectations for patients with higher proteinuria at. You expect them to have a greater, Yeah, yeah. Yeah, and I'll just add also, and I again, we would expect a slightly lower urine protein level, right? We have a lower entry criteria, just the first question, right? And as far as the percent reduction, we did see a slightly prognary reduction in duet and duplex above and below the product ring, but it was slightly diminished in the higher group compared to the lower group.

And bill to the question around power.

Oh and a per calorie.

We're powered at 90% to show a 30 per cent relative production and progeria on the interim analysis and point and that is.

Gives us what we believe to be a very clinically relevant reduction in proteinuria and more importantly per.

<unk> Ah clinically relevant.

Reduction in Egfr loss or preservation of Egfr slope. So that's how.

This study is powered.

And I guess, the I guess, the other piece that I would I.

I would mention when we talk about.

On on your first question round heterogeneity.

With our study we have inclusion exclusion criteria that really are designed to control that heterogeneity on the entrance to the study so that we get a pretty even group of patients.

Lisa Beiko: So, you know, we might expect that. But remember that in IGA, we have a less pro-neuric population than we do in FSGS, so probably, it wouldn't have as much of an impact as we had to predict. But, again, we'll have data back in August, and we'll know that for sure. Got it. Okay. From Evercore ISI, we have Lisa Beiko. Please go ahead.

With similar baseline characteristics.

Mhm.

That's great no is there anything else that you wanted to add on on that one.

Yeah, I think I agree with everything that bill, saying I think when you're in the in the setting of clinical trial.

Randomised phase III study, we have the opportunity here to treat patients with specific include drinks, we proprietary so having a UPC greater than one English is his pocket then doing things like having it on <unk> standardized control on there.

Eric Dube: Hi, yeah, just, I just want to clarify. Is it your expectation that you're going to file an accelerated approval? Just to clarify, because it's just the way you phrase it. I want to make sure that it's your expectation that you are going to file for accelerated approval based on the data you have, correct?

Is critical to ensure that we have a stringent interpretation of the results.

These studies on the backgrounds and standards of care or different and they're profitable. So I think by providing that standard of care on.

Lisa Beiko: Hi Lisa, yes, so accelerated approval is our base case, and we're currently planning and writing the NDA for that, but obviously, that's going to be subject to the ongoing interactions with regulators, and you know, that's something that we'll be able to provide updates on later this quarter. And I think that's also why we want to make sure that we're engaging very closely with FDA so that we understand, you know, their expectations for the past and reviewing the data with them prior to submission so that we have an aligned approach to accelerated approval.

Standard or a a certain dose on for every patient and find Richie again with UPC and getting population, it's it's a little more uniform.

Yeah, like we're pretty good shape, if you compare across the duplex.

Felt when we're going into average just that was a much more ah.

A much more.

Diverse population on <unk>, and we were able.

Able to show the support of numbers and in fact, and so I think besides the study on there is also important to point out having fairly 80 patients gives us that ability to a lot of those studies that bill cited are really smaller studies and so I think those are some of the while we feel confident scribble progressive and also the statistical analyses are very robust.

As well so I think those are some of the keys.

Eric Dube: And then, can you maybe just review, like, separately for FSGS and for IJ Napropathy, what kind of, uh, what gives you confidence that you can file on Accelerer Approval, notwithstanding the data, but using Protonuria, this idea of using Protonario, can you maybe review what's in the public domain or what's been communicated with FDA that you know, lead you to believe that Yes, sir.

Thanks, though.

From BMO capital markets, we have <unk>. Please go ahead.

Hi, everyone. Thanks for taking my question.

I was hoping that you could go over your expectations for what the FDA is looking for.

During these interaction.

Back when you.

Or the company had the end of phase two meeting and and the F. D ended up requesting a phase three study.

They confirm that potent Maria reduction.

Patel.

Potentially approvable endpoint, they wanted a longer treatment duration.

William E. Rote: Yes, certainly, and I'll ask Bill to take that one. Certainly, if we start with the public domain, there's a growing body of literature that links reductions in proteinuria to preservation of renal function in the long term, and specifically the work coming out of Dr. Inker's lab and others, Trust is another out of Michigan, and Troyanov, all are showing a consistent story that reductions in proteinuria confer a slowing of the decline of renal function. In all of us, we have a lower GFR year by year as we age. In these patients with pulmonary diseases, that rate is fast.

What drove that.

Other aspects of the interim data that they are specifically interested in like.

Like safety or.

<unk>.

Do let me let me.

Take this one on our last bill to provide any further comment.

The expectation that we have for our regulatory submission on <unk> is a.

Clinically meaningful statistically significant reduction in preliminary which we provided in February as we mentioned the confirmatory endpoint will be on Egfr and certainly we believe that they're going to be looking at safety in the totality of evidence and I think because in many ways, we're charting a new path and the use of protein area.

In this trial design. This is why very much we're engaging with them.

And sharing within the data so that we get a line on what they need to free for accelerated approval I think at this point that as much as I would be able to say in terms of expectations, but a last bill to provide anything further from his perspective.

Eric I I agree with everything that you say I think the only color that I would add to that.

William E. Rote: If you're able to reduce the proteinuria in these patients, that's expected to and has been shown to confer a reduction in EGFR levels. To answer your question, we have been in discussions with the agency as well as the EMA in Europe around trial design, with the surrogacy of proteinuria at an interim endpoint being used to predict the reductions in EGFR at the two-year confirmatory end. So the combination of both what's in the public domain and the dialogue we've had with regulators gives us confidence that this is a path that they are aligned with that could be used for an accelerated approach.

Is in this situation with accelerated approval being based off of the surrogate endpoint.

In addition to the totality of the day to the agency is going to need to see or want to see enough evidence that provides a clear picture of the prediction of reduction in protein area to preservation of Egfr net would be significant at the two year endpoint.

Then.

Part of why we are currently engaged with the agency, making sure. That's a submission that we put forward meets their needs.

HM HM.

Great that's helpful.

And a question for Laura.

William E. Rote: And I think the other aspect, Lisa, is that there is consistency in how other sponsors who've obviously engaged with FDA have designed their programs and the use of progenia. So I think that consistency, while we can't speak to other programs, is reassuring in the approach that we've received and the guidance that we've received. Okay, thank you.

Could you provide some additional <unk> color on the quarter over quarter step up and R&D expenses is.

Is it broadly from all of a simple studies or.

Does it primarily from the addition of the HEU program.

Hi, Joe Yeah really.

A combination of all of that so yes, you're correct.

Thank you that needs program. This is the first.

Timothy Francis Lugo: Thanks, Lisa. From William Blair, we have Tim Lugo. Please go ahead. Hi guys, this is John on behalf of Tim. Thanks for taking our question. I was just wondering if you guys could provide some commentary on how payer discussions are going for Sparsenten and FF, and maybe a bit more specifically, if you could provide some color on how the payers are responding to and thinking about the interim protein urea data. John, thanks for your questions. And Peter, would you like to take this one?

Accorded that we've had that program here at <unk> and then in addition.

It continuing.

Steady progression for gifts like 10 free cash and just recall debt.

Eight continue on to their Egfr endpoints in 2022.

So it continued monitoring.

Assessment, so that required investment so it is a cross stitch there's programs that you mentioned.

Perfect.

Thanks for taking my question.

Yeah.

We have no further questions at this time.

Peter Heerma: Yeah, thanks for that question. I think it kind of built on the conversation that Bill was just outlining how the relationship between Pottenurea reduction translates into reduction of progression of disease and ultimately delay of end-stage kidney disease. And I think some of the work that we have done is informative to have those conversations with players. You may remember the R&D day where Dr. Barrett was presenting how a 30% reduction in Pottenuria actually translates into an IGA infratopathy.

Great. Thank you Brandon and thank you all for joining US today. This concludes our call for the first quarter. If we look forward to providing you updates on our progress on the near future. Thank you and have a great rest of the week.

Thank you ladies and gentlemen. This concludes today's conference. Thank you for joining you may now disconnect.

Peter Heerma: patient level base, to about over 10 years delay of end-based kidney disease. And we are in the process right now to do similar work for FSGS. And I think that's the kind of data that payers are very interested in to gain an understanding of what the translation of proteinuria reduction is into ultimately hard endpoints in delay of progression of results.

Peter Heerma: All right, thanks so much for that color. From Kandakar Genuity, we have Michelle Gilson. Please go ahead. Hi, this is Michael Conventi on behalf of Michelle.

Michelle Gilson: Congratulations on the quarter. So for the duplex filing, and I got some questions about Spharcenta, so it seems like you are engaging with regulators. I guess more specifically, does the filing for FSGS come before or after the interim for touch data in IDAN and then sort of a little more broadly? Do you see any re-through to the FDA?

Michael Conventi: to the FDA, recently accepting other applications for rare glomerular diseases, to the agency's view of what the complete data package would be for these diseases.

Eric Dube: Michael, thanks so much for your questions. And with regard to your first question on the timing of filing and whether that would occur before or after the Protect interim, we wouldn't be in a position today to comment on the sequencing of that, but we are on track to provide both the data from Protect in the third quarter, and then we'll provide an update on our regulatory interactions later this quarter. So that may be something that we can provide.

[music].

Eric Dube: greater detail on very soon. With regard to read-through of recent regulatory filings, I would say, you know, a couple of things. One is that, certainly, there is recognition of significant unmet need, very much in what I shared in my prepared marks with regard to rare kidney disorders. And we believe, based on our interactions, that regulators clearly understand this need.

Eric Dube: And, you know, we're encouraged by other progress in other programs, just given that it's, you know, several steps closer for patients to potentially have an approved therapy. But each program is different, and so we can't really make comparisons between those, and I certainly wouldn't want to draw conclusions anyway about our programs. You know, our focus is to continue the trials and to continue our NDA preparation, and, you know, as I mentioned, we're in the process of engaging with regulators, so we'll be able to provide an update soon.

Michael Conventi: Excellent, thank you. Just switching gears, just one more, actually switching to TBT 058, which is now newly named Peggy Tibetan. So it looks like there's

Michael Conventi: So it looks like there's a potential delay due to COVID. You mentioned an impact on opening new sites. Is there any other way that COVID is affecting the trial? Perhaps, you know, issues with already open sites or anything else you haven't discussed. Thank you so much.

William E. Rote: Great, thanks for the question. Bill, would you like to provide your thoughts on that? Certainly, the trial has not been free of impact from COVID, as you note. I think about your question about specific sites. It depends on the site, and it depends on the timing. There have been certain times during the past 12 months when some of these centers, some of which are children's hospitals, have not been open to anybody except for specific patients.

William E. Rote: In that exclusion list would be somebody in a clinical trial potentially that might be on placebo, as an example. This is something that's dynamic, as our lives have all been throughout the last year with COVID. We are seeing these restrictions ease as the rates of COVID have come down around the nation, but it's very individualized, center by center and month to month. We've responded to these by looking at the protocol and changing some of the visit schedules.

William E. Rote: For example, using nurses that go to the home to collect samples as opposed to patients having to come into the hospital for a visit in order to maintain the progress, the forward momentum in this study, and also not to miss key samples or key data points.

Michael Conventi: Excellent. Thank you. That's all for me.

Laura Kathryn Chico: from Wedbush Securities. We have Laura Chico. Please go ahead.

Laura Kathryn Chico: Thanks very much for taking the question. Apologies if this was already asked. I know you mentioned the Inker publication, but I just wanted to circle back with one on Protect. So one of the limitations mentioned in the Inker paper was the heterogeneity of the trial data that they examined. And so I was just wondering if you could talk about how you've tried to address that with the Protect Study and also maybe your assumptions around statistical powering.

William E. Rote: Thank you, Laura. Bill, I'll ask you to take this.

William E. Rote: Sure, I think the challenge with the Inker paper is not unusual in the rare disease community in that there aren't a lot of clinical trials to draw on. For example, if you're doing a meta-analysis in the cardiovascular space, you're going to pull 75 studies and whittle them down to an exclusion criteria to the 50 that really matter. In the case of the Inker publication, they basically took all the treatment studies, interventional studies in IGA nephropathy and grouped them together, taking out those that might be different for this reason or that would leave them with two small sample sets.

William E. Rote: So the end result was the input was a fairly heterogeneous group. I think the consistent message coming, well, and the result of that is they cited as one of the potential weaknesses the analysis, but also it results in a greater uncertainty in the measure when you start to look at the correlation and draw regression, If you look at the signal overall and the consistency of the mess It's clear with the analyses that have been done by others, as well as the work that we have done internally with registry data and other data in that reductions in proteinuria are linked, Preservation of Reno.

William E. Rote: So the, I don't think that the heterogeneity cited in the Inker paper is something of a concern. I think it was an apt description of their input data, but I think the output message in it was really quite, Bill, to the question around powering.

[music].

William E. Rote: Oh, in powering, we're powered at 90% to show a 30% relative reduction in proteinuria on the interim analysis endpoint, and that gives us what we believe to be a very clinically relevant reduction in proteinuria, and more importantly, predicts clinically relevant reductions in EGFR loss or preservation of EGFR slope. So that's how the study is powered. And I guess the other piece that I would mention when we talk about your first question around heterogeneity. With our study, we have inclusion and exclusion criteria that really are designed to control that heterogeneity at the entrance to the study so that we get a pretty even group of patients with similar baseline care. That's great. No, is there anything else that you wanted to add to that one?

Noah Rosenberg: Yeah, I think I agree with everything that Bill said. And I think when you're in the setting of a clinical trial, a randomized phase three study, we have the opportunity here to take patients with specific inclusion and exclusion criteria. So having a UPC greater than one enriches this population; doing things like having an herbicide and standardized control is critical to ensure that, you know, we have a stringent interpretation of the results. You know, in these studies, the backgrounds, and standards of care are different, and they're very tools.

Noah Rosenberg: So I think by providing that standard of care, the standard or recommended dose for every patient, and by enriching, again, with UPC and getting a population that's a little more uniform, I think, I feel like we're in pretty good shape. You know, if you compare across the duplex, you know, we felt when we were going into FHIS that it was a much more diverse population, a heterogeneous population, and we were able to show that with similar numbers and effect.

Noah Rosenberg: And so I think the size of the study is also important to point out. Having, you know, 3080 patients gives us that ability. A lot of those studies that build are really, you know, smaller studies. And so I think those are some of the reasons we feel confident we're able to address it. And then also, the statistical analyses are very robust as well. So I think those are some of the keys. Thanks, from BMO Capital Markets. We have Doe Kim.

Doe Kim: Please go ahead. Hi everyone. Thanks for taking my question. I was hoping that you could go over your expectations for what the FDA is looking for during these interactions. Back when you or the company had the end of phase two meeting and the FDA ended up requesting a phase three study, they confirmed that protein reabsorption is a potentially approvable endpoint, but they wanted a longer treatment duration. What drove that? Are there other aspects of the interim data that they are specifically interested in, like safety or EGFR trends? Doe, let me take this one, and I'll ask Bill to provide any further comments.

[music].

Eric Dube: You know, the expectation that we have for a regulatory submission on FSGS is a clinically meaningful, statistically significant reduction in proteinuria, which, you know, we provided in February. As we mentioned, the confirmatory endpoint will be EGFR, and certainly, we believe that they're going to be looking at safety and the totality of evidence. And I think because, in many ways, we're charting a new path in the use of proteinuria in this trial design, this is why we are very much engaging with them and sharing with them the data so that we can align on what they need to do for accelerated approval.

Eric Dube: I think at this point that's as much as I would be able to say in terms of expectations, but I'll ask Bill to provide anything further from his perspective. Eric, I agree with everything that you say. I think the only color that I would add to that is, in this situation with accelerated approval being based on a surrogate endpoint, in addition to the totality of the data, the agency is going to need to see or want to see enough evidence that provides a clear picture of the prediction of reduction in proteinuria to preservation of EGFR that would be significant at the two-year endpoint.

Eric Dube: You know, that's part of why we're currently engaged with the agency, making sure that the submission that we put forward meets their needs. Buhn. Great, that's helpful. And a question for Laura, could you provide some additional color on the quarter-over-quarter step-up?

William E. Rote: in R&D expenses. Is it broadly from all the

Doe Kim: from all the clinical studies, or is it primarily from the addition of the HCU program?

Laura Kathryn Chico: Hi Doe, yeah, really, it's a combination of all of that, so yes, you're correct as far as the Big Tabatinase Program is concerned.

Laura Kathryn Chico: This is the first school quarter that we've had that program here at

Laura Kathryn Chico: and then, in addition, it's the continuing study progression for duplex and protect, and just recall that those studies continue on.

Laura Kathryn Chico: on to their EGFR endpoints in 2020.

Laura Kathryn Chico: So there's continued monitoring.

Laura Kathryn Chico: Assessment, so that requires continued investment. So it is across those programs that you mentioned. Perfect. Thanks for taking my questions. Thank you, Doctor. We have no further questions at this time. Great, thank you, Brandon, and thank you all for joining us today. This concludes our call for the first quarter. We look forward to providing new updates on our progress in the near future. Thank you, and have a great rest of the week. Thank you, ladies and gentlemen. This concludes today's conference. Thank you for joining. You may now disconnect.

Brandon: Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you.

Brandon: Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you. Thank you.