Q2 2019 Earnings Call

Unknown Executive: © BF-WATCH TV 2021 Ladies and gentlemen, thank you. The conference call will begin momentarily. Until that time, you'll answer a big, Again, ladies and gentlemen, thank you, conference call will begin till the time you learn so ??? ??? ??? ??? ??? ??? ??? ??? ??? ??? ??? ??? Good afternoon ladies and gentlemen and welcome to the Retrofane, 2nd quarter of 2008. International Results and Corporate, At this time, all participants are in, We will conduct a question and answer session and instructions will follow. If anyone should require, Conference, please press star with the number zero on your phone. As a reminder, this conference call, I'd like to turn the conference over to your host. Thanks, Rusty.

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Again, ladies and gentlemen, thank you for standing by.

The conference call will begin momentarily.

Unknown Executive: Good afternoon, everyone, and welcome to Ritrofen's second quarter 2019 financial results and corporate update call. Today's call will be led by our Chief Executive Officer, Dr. Eric Dube. Eric will be joined for the prepared remarks by our Chief Medical Officer, Dr. Noah Rosenberg, and our Chief Financial Officer, Laura Clay. Dr. Bill Rote, our Senior Vice President of Research and Development, will join us for the Q&A. Before we begin, I'd like to remind everyone that statements made during this call regarding matters that are not historical facts are forward-looking statements within the Safe Harbor Protocol, the Private Securities Litigation Reform Act of 1995. Forward-looking statements are not guarantees of performance. They involve known and unknown risks, uncertainties, and assumptions that may cause actual results, performance, and achievements to differ materially from those expressed or implied by the statement. In addition, any forward-looking statements represent our views only as of the date such statements are made, August 6, 2015, and Retrophin specifically disclaims any obligation to update such statements to reflect future events. With that, I now turn the call over to Eric.

Until that time your lines will be inflation home.

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Good afternoon, ladies and gentlemen.

Retrophin Inc. second quarter, 2019 financial results and corporate update call.

Eric Dube: Thank you, Chris, and good afternoon, everyone. It's an exciting time for Ritropin. Our team members and leadership continue to demonstrate an unwavering focus on execution and delivering new treatment options for patients living with rare diseases. Core to our mission is the focus on developing innovative treatments like Fosmin, Pantotenate, and Sparsantin as potential first-in-class treatments. A number of team members and I recently had the honor of attending a patient community meeting and hearing directly from patients and parents about the challenges of living with PECAN and the desperate need for an approved treatment. We've been working for the past several years in an effort to bring treatment to the PECAN community. We believe Fosmet Pantotenate has the potential to help fill the significant unmet need and to become the first approved therapy to give these families hope. The key to making Fosmet Pantotenate available for patients with PKIN is our ongoing Phase 3, 4 study. I am pleased to report that everything remains on track for us to obtain and share top-line results later this quarter.

At this time, all participants I don't listen only mode.

HM we conduct a question answer session and instructions will follow what the time.

If anyone should require assistance during the conference. Please press Star then the number Joe on the telephone keypad.

As a reminder, this conference call is being recorded.

I would like to turn the conference over to your host Mr., Chris Cline may begin Sir.

Thanks, Rusty good afternoon, everyone welcome to the drop in second quarter, 2019 financial results and corporate update call.

Today's call will be led by our Chief Executive Officer, Dr. today, Eric will be join for the prepared remarks by our Chief Medical Officer, Dr., No Rosenberg and our Chief Financial Officer, Mark like.

Dr. Bill route for senior Vice President of research and development will join us for the QNX session.

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

Forward looking statements are not guarantees of performance they involve known and unknown risks uncertainties and assumptions that may cause actual results performance and achievements to differ materially from those expressed or implied by.

Disclaimer on the Companys press release issued earlier today as well as the risk factor section in our forms 10-Q, and 10-K filed with the SEC.

Eric Dube: While we remain blinded to the data, we are planning for success and positioning ourselves to move quickly to file our NDA and MAA submissions in 2020 in the event of positive results. In addition, we are making sound progress with launch readiness activities. We now have in place key roles such as market access, medical affairs, and marketing to be ready to support launches in the U.S. and Europe. Sparsentin also advanced in our two Phase III studies during the quarter, and we continue to build our position as a leader in rare glomerular disease. The growing support for sparsentine's potential to become the new treatment standard for conditions like FSGS and IGA nephropathy is underpinning our position of strength.

In addition, any forward looking statements represent our views only as of the date such statements are made August six 2019, and Retrophin, specifically disclaims any obligation to update such statements to reflect future information events or circumstances.

With that let me now turn the call over there.

Thank you, Chris and good afternoon, everyone. It's an exciting time for which reopened our team members and leadership continue to demonstrate an unwavering focus on execution and delivering new treatment options for patients living with rare disease core to our mission is to focus on developing innovative treatments like Faulkner tend to Nate and Sparsentan as potential first in class treatment.

A number of team members and I recently had the honor of attending a patient community meeting and hearing directly from patients and parents about the challenges of living with Pete here and the desperate need for an approved treatment.

Eric Dube: Our lead study duplex in FSGS continues to open new sites globally. However, as we learned through our Phase 2 duet study, enrollment in FSGS can be difficult to project at times. In recent months, enrollment trends in duplex have not increased at the rate we had forecasted during the beginning of these critical summer months.

We've been working for the past several years in an effort to bring a treatment to the P. 10 community. We believe Paul Smith and took me has the potential to help fill the significant unmet need and to become the first approved therapy to give these families hope.

The key to making fog that pad to make available for patients with P., Ken is our ongoing phase three fourth studies.

Eric Dube: Importantly, given our experience with Duet, we were prepared and moved quickly to accelerate planned initiatives when this arose. Those initiatives are already starting to have a positive impact on screening and enrollment. However, based upon where we stand today, we believe it would be appropriate to adjust our guidance for top-line results of the proteinuria endpoint from the second half of 2020 to the first half of 2021. I remain confident in our team's ability to execute.

I am pleased to report that everything remains on track for us to obtain and share topline results later this quarter.

While we remain blinded to the data we are planning for success and positioning ourselves to move quickly to file our NDA and MAA submissions in 2020 in the event of positive results.

In addition, we are making sound progress with launch readiness activities. We now have in place key roles such as market access medical affairs, and marketing to be ready to support launches in the U.S. in Europe .

Eric Dube: We recognize that any delay in getting this treatment to patients is meaningful, so we are continuing to act with a great sense of urgency while maintaining the high quality of study recruitment we have seen thus far. Over the balance of the year, our goal will be to ensure our initiatives for enrollment accelerate these timelines, if possible.

Sportscenter and also advance in our two phase three studies during the quarter and we continue to build our position as a leader in rare gloom area other diseases.

The growing support for spar sentence potential to become the new treatment standard for conditions like Fscs and RJ nephropathy is underpinning our position of strength.

We've studied duplex in Fscs continues to open new sites globally.

Eric Dube: Our Phase 3 PROTECT study in IgA nephropathy is progressing nicely, and we are seeing strong execution across sites. The team is doing a good job of leveraging the lead work and footprint forged by Duplex to drive considerable participation in the study, and we remain on track to have top-line proteinuria results in the first half of 2022. Further, in our research and development efforts during the second quarter, we entered into a Cooperative Research and Development Agreement, or CRADA, which is dedicating early research efforts towards the identification of potential therapeutics for allergical syndrome. Allergial syndrome is a rare and debilitating disease characterized by severe liver and cardiovascular abnormalities.

As we learned through our phase two duet study enrollment in SSG EPS can be difficult to project the times.

In recent months enrollment trends in duplex have not increased at the rate we had forecasted during the beginning of these critical summer months.

Importantly, giving our experience with duet we were prepared and moved quickly to accelerate planned initiatives. When this arose those initiatives are already starting to have a positive impact on screening and enrollment.

However, based upon where we stand today, we believe it would be appropriate to adjust our guidance for topline results of the proteinuria and point from the second half of 2020 to the first half of 2021.

I remain confident in our teams ability to execute.

We recognize that any delay in getting this treatment to patients is meaningful. So we are continuing to act with a great sense of urgency while maintaining the high quality of study recruitment we have seen thus far.

Eric Dube: And there are currently no approved therapies. In this collaboration, we're working with the NIH's National Center for Advancing Translational Sciences and the AllerGeal Syndrome Alliance, the leading allergen patient advocacy foundation. This is our second CRADA with NCATS, and it establishes our innovative strategy of collaborating with leading scientists and patient communities to advance early research. By pooling resources with the best talent, we believe this allows us to take a disciplined approach to increasing our probability of success in identifying new treatment pathways. It also allows for our operational teams to remain clearly focused on our late stage program. We look forward to updating you in the future as these collaborations progress. I'll briefly touch on our decision to decline to exercise our option to acquire CENSA and, accordingly, to discontinue the joint development program for CNSA 001 in PKU.

Over the balance of the year, our goal will be to ensure our initiatives for enrollment accelerate these timelines if possible.

Our phase three protect study in Jena property is progressing nicely and we are seeing strong execution across sites.

The team is doing a good job of leveraging the lead work and footprint forged by duplex to drive considerable participation. In this study and we remain on track to have topline probably already results in the first half of 2022.

Further on our research and development efforts during the second quarter, we entered into a cooperative research and development agreement or Credo, which is dedicating early research efforts towards the identification of potential therapeutics for allergy Alcentra.

Hello, Joe syndrome is a rare and debilitating disease characterized by severe liver and cardiovascular abnormalities and there are currently no approved therapies.

Eric Dube: We recently completed our review of the Phase II program in PKU. While there may be potential for CNSA-001 to ultimately become a treatment option for PKU, it did not meet Ritrofen's specific requirements for acquiring sensopharmaceuticals. SINSA has a talented drug development team, and we are very thankful for their collaboration over the last 18 months. Consistent with our patient focus and mission of delivering life-changing therapies, we will look to further diversify our pipeline with additional programs that focus on areas of high unmet need. Turning to the base business, I'm very pleased with our commercial team's continued execution. We had a strong second quarter and delivered another quarter of year-over-year net product sales growth. This was driven primarily by new patients initiating treatment with all three of our approved products. Biola's performance remains steady.

In this collaboration we're working with the NIH is National Center for advancing translational Sciences, and the allergy Olson from alliance the leading eligible patient advocacy Foundation. This is our second created with Encana and it establishes our innovative strategy of collaborating with leading scientists and patient communities to advance early research by pooling resources with the best talent. We believe this allows us to take a disciplined approach to increasing our probability of success and identifying new treatment pathways.

It also allows for our operational teams to remain clearly focused on our late stage programs. We look forward to updating you in the future as these collaborations progress.

I'll briefly touch on our decision to decline to exercise our option to acquire senza and accordingly to discontinue the joint development program for CNS, a 001 in PK you.

Eric Dube: Notably, we started off the summer with the approval of Fiola EC, a great step forward in the Cystinuria community that will provide a new treatment choice for patients. Fiola's utility in cystitinuria has been well-established, but we know there are some patients who face challenges with the original formulation. Two of the most common challenges we heard from patients were that there can often be a high pill burden and that it can be difficult to remain compliant when taking the original formulation one hour before or two hours after meals, particularly when many patients are also prescribed potassium citrate, a concomitant medication that is indicated to be taken with food three times a day. Importantly, Fiola EC is indicated to be taken with or without food, which should provide a welcome element of freedom for administration.

We recently completed our review of the Phase two program in T.K. you.

While there may be potential for CNS, eight zeros or one to ultimately become a treatment option for PK you. It did not meet retrophin specific requirements for acquiring Synta pharmaceuticals.

That's a has a talented drug development team and we're very thankful for their collaboration over the last 18 months.

Consistent with our patient focus and mission of delivering life changing therapies, we will look to further diversify our pipeline with additional programs to focus on areas of high unmet need.

Turning to the base business I'm very pleased with our commercial teams continued execution, we had a strong second quarter and delivered another quarter of year over year net product sales growth.

This was driven primarily by new patients initiating treatment with all three of our approved products.

Violence performance remained steady.

Notably we started off this summer with the approval of Faiola you see a great step towards forward into cystinuria community that will provide a new treatment choice for patients.

Eric Dube: And the Fiola EC 300 milligram option provides patients with the potential to reduce the number of tablets necessary to manage their cystineuria. Our launch is underway, and I am pleased to report that the first Thiola EC prescriptions were shipped to patients as planned at the end of July. Our commercial team has done an excellent job of making this new option available to patients within weeks of approval, and we are encouraged by the early reception the new brand is getting from prescribers and patients. Our approach is simple.

Violence utility insistent area has been well established but we know there are some patients who face challenges with the original formulation.

Two of the most common challenges we heard from patients where there can often times be a high tilburg and that it can be difficult to remain compliant when taking the original formulation one hour before or two hours after meals, particularly when many patients are also prescribed potassium titrate a concomitant medication that is indicated to be taken with food three times a day.

Eric Dube: We are providing patients with a choice of which therapy they and their physicians believe is best for managing their cystinemia. We are ensuring clear access to both forms of thiola, and we do not have plans to remove the original formulation. FIOLEC is available at the same price as the original formulation.

Importantly, viola AC is indicated to be taken with or without food, which should provide a welcome element of freedom for administration.

And finally, he says 300 milligram option provides patients with the potential to reduce the number of tablets necessary to manage their cystinuria.

Noah: Importantly, our market research tells us that there is likely to be significant demand from new and current patients who would prefer the additional flexibility and convenience that Biola EC offers. And it also tells us that there is an opportunity for patients who may have discontinued phyla treatment over the years to revisit the brand and see if they may find benefits from the new formulation. As a result, we're confident in the outlook for the franchise. While there is limited data to share given the very recent launch, we look forward to giving more detail about the uptake of Viola EC in the coming quarters, once we have more time engaging with physicians and gathering additional feedback from patients. Regarding our bile acid portfolio, we were pleased with the recent strong performance, which was driven by new patient starts across the products during the second quarter.

Our launches underway and I'm pleased to report that the first file that you see prescriptions were shipped to patients as planned.

At the end of July .

Our commercial team has done an excellent job of making this new option available to patients within weeks of approval.

And we are encouraged by the early reception, the new brand of getting from prescribers and patients.

Our approach is simple.

We are providing patients with a choice of which therapy, they and their physicians belief is best for managing their cystinuria, we are ensuring clear access to both forms of firewall.

And we do not have plans to remove the original formulation and file E. C is available at the same price as the original formulation.

Importantly, our market research tells us that there is likely to be significant demand from new and current patients who would prefer the additional flexibility and convenience that file that you see offers.

And it also tells US that there is an opportunity for patients who may have discontinued faiola treatment over the years to revisit the brand and see if they may find benefit from the new formulation.

As a result, we're confident in the outlook for the franchise.

Noah: Overall, our commercial team has shown an ability to drive consistent organic growth over the last several years. This gives us great confidence going into the critical period of the ongoing FIOLA-EC launch and, ultimately, for maximizing the potential for Fosmet, Pantotenate, and Sparsentin if approved. I will now turn the call over to Noah for some updates on the pipeline. Noah? Thank you.

While there is limited data to share given the very recent launch we look forward to giving more detail about the uptake of file that you see in the coming quarters. Once we have more time engaging with physicians and gathering additional feedback from patients.

Regarding our bio asset portfolio, we were pleased with the recent strong performance, which was driven by new patient starts across the products during the second quarter.

Overall, our commercial team has shown an ability to drive consistent organic growth over the last several years.

Noah: Thank you, Eric, and good afternoon. I'll start with the FOSMET Pantotenate Program and our novel substrate replacement therapy being evaluated for the treatment of pantothenic kinase associated neurodegeneration, or PCAN. We are nearing the top line readout from the FORT study, which is our pivotal phase three trial being conducted under a special protocol assessment agreement, or SPA, with the FDA. The FORT study enrolled 84 patients with PCAN and will measure changes in the PCAN activities of daily living scale, or PCAN ADL, in patients receiving either fosmid pantothenate, or placebo. The primary endpoint of this study will evaluate the average change in PK and ADL from baseline after 24 weeks of treatment.

This gives us great confidence going into the critical period of the ongoing file that you see launch and ultimately for maximizing the potential for fog meant penta, Nate and four cents and if approved.

Let me now turn the call over for Noah for some updates on the pipeline no.

Thank you Eric and good afternoon.

I'll start with the fossett pad totally program.

Our novel substrate replacement therapy being evaluated for the treatment of Pantothenate kinase associated neuro degeneration.

Or p., Ken we are nearing the topline readout from the Fort study, which is our pivotal phase three trial being conducted under a special protocol assessment agreement or spa with the FDA.

Noah: And it's power to show them.

The Fort study enrolled 84 patients with P. Ken.

Noah: As outlined in our SPA agreement, a three-point change in this scale will be measured. I'm looking at change from baseline to end of study in the PKL-ADL score at each visit through 24 weeks. While we remain blinded to the data, we continue to be very pleased with the conduct of the study, and our clinical biometrics teams and our CRO are working to complete our data validation activities. As we mentioned on our last call, the baseline characteristics of the study include a baseline PK and ADL score in the upper 20 range, and are consistent with the representative population as well as what we have seen with the four patients outside United who remain in their physician-in [inaudible] done to validate the PK and ADL scales. Also, the variability of the overall population, we're looking at the study on a blinded basis, is within the expected range to support the powering of Ford. These two key points give us confidence.

And we'll measure changes in the P. can activities of daily living scale or pecan acres.

Well in patients receiving either positive pantothenate.

Excuse me or placebo.

The primary endpoint of this study will evaluate the average change in the PK and HDL from baseline. After 24 weeks of treatment and is powered to show a three point difference between treatment groups.

As outlined in our spot agreement of three point change in the scale will be considered clinically meaningful for patients and physicians.

The treatment effect will be measured.

Looking at the change from baseline Peaky.

From baseline to end of study in the peak HDL score at each visit through 24 weeks.

While we remain blinded to the data we continue to be very pleased with the conduct of the study and our clinical biometrics teams and our COO are working to complete our data validation activities.

As we mentioned on our last call. The baseline characteristics of this study include a baseline pecan HDL score and the upper 20 range and are consistent with a representative population as well as what we have seen with the four patients outside United States, who remain in their physician initiated programs and with the work.

Noah: [inaudible] At this point, all patients who completed the double blind portion of the study entered the open label extension and are continuing with the study. We now have some patients in Fort who have been receiving therapy for more than two years. Given the continued participation in the Open Label Extension, we anticipate having a robust data set to examine to support our NDA and MAA filings if forked data are positive. Our development team is advancing our regulatory submission materials, and we are well positioned to submit our filings in 2020. I'll now shift over to SportsFed.

Don to validate the pecan HDL scale.

Also the variability of the overall population we're looking at the study on a blinded basis is within the expected range to support the powering afford these two key points give us confidence in the study design.

At this point all patients who completed the double blind portion of the study entered the open label extension and our continuous study visits we now have some patients in fourq, but receiving therapy for more than two years.

Noah: During the second quarter, we continued to engage with thought leaders and physicians at key medical conferences like ERA and EDTA. The recurring theme in all of our discussions is that there is a significant unmet need for both FSGS, or focal segmental glomerulosclerosis, and IJ nephropathy. Specifically, physicians are eager to explore non-immune suppressive treatment options or non-ISPs with a potential profile that would be appropriate for the long term. Continue to believe and hear from our advisors that our pivotal Phase III duplex and PROTECT studies are well-designed to evaluate how Sporcentin could work as a treatment option for patients and nephrologists. Potentially position sparse hand-to-hand as a therapy of choice in rare rheumatoid arthritis. During the second quarter, we had our first scheduled data monitoring committee meeting for both duplex and protect, and I'm pleased to report that the DMC recommended.

Given the continued participation in the open label extension, we anticipate having a robust data set to examine and to support our India in EMEA filings at Fort data are positive our development team is advancing our regulatory submission materials and we are well positioned to submit our filings in 2020.

I will now shift over to Sparsentan.

During the second quarter, we continue to engage with thought leaders and physicians at key medical Congresses like era.

The recurring theme in all of our discussions is that there is a significant unmet need in both fscs or focal segmental glomerulosclerosis and chain of frothy.

Specifically physicians are eager to explore non immune suppressive treatment options are biased non I estes with a potential profile that we would be appropriate for long term use we continue to believe and hear from our advisors that our pivotal phase three duplex and protect studies are well designed to evaluate how sparsentan could work as a treatment option for patients and nephrologist and potentially position sparsentan as a therapy of choice in rare renal disease.

Noah: The Valuing the Nephro-Protective Potential of Sparse Antennae in FHES to enroll, and we remain pleased with the conduct of the study. As Eric mentioned, the rate of enrollment is not at our expected pace in recent months, but we've been able to act quickly to move up the implementation of some of our planned initiatives. For example,

During the second quarter, we had our first scheduled data monitoring committee meeting for both duplex and protect and I'm pleased to report that the DMC recommended to proceed as planned with both studies.

Do plugs, which is evaluating the net for protective potential of Sparsentan in Fscs continues to enroll and we remain pleased with the conduct of the study.

Noah: Recently, we accelerated activities with partners at registries and renal pathology centers to broaden the reach for referring eligible patients to the study. We know from our experience with DUET that there are significant numbers of patients outside of academic sites or centers of expertise. These referral efforts allow us to reach a broader population, and we are seeing promising momentum as a result. Most importantly, we continue to be very confident in the Product of the Study and that we are getting the right patients enrolled. This gives us increasing confidence. [inaudible] Our Phase 3 PROTECT Study evaluating the potential of sparse ventin in IgA nephropathy remains on track.

As Eric mentioned the rate of enrollment did not increase at our expected pace in recent months, but we've been able to act quickly to move off the implementation of some of our planned initiatives.

For example, we recently accelerated activities with partners I registries and renal pathology centers to broaden the reach for for eligible patients in the study.

We know from our experience with duet that there are significant numbers of patients outside of academic sites or centers of excellence. So these referral efforts allow us to reach a broader population.

We are seeing promising momentum as a result of these efforts. Most importantly, we continue to be very pleased with the conduct of the study.

Laura: Our clinical teams have done an exceptional job of leveraging the knowledge we've obtained and the footprint we've built while rolling out the duplex study. That has allowed us to develop tailored best practices and drive engagement in PROTECT, and we are seeing that translate to strong enrollment trends. I will now turn the call over to Laura for a financial update. Thank you, Noah.

And that we are getting the right patients enrolled and duplex. This gives us increasing confidence in the potential to have a positive outcome from this study and deliver a new treatment standard for Fs, yes.

Our phase three protect study, which is evaluating the potential of Sparsentan egina property remains on track.

Our clinical teams have done an exceptional job of leveraging the knowledge, we have obtained and the footprint, we adult while rolling out the duplex study.

Eric Dube: During the second quarter, net product sales from our commercial portfolio grew to $44.7 million, an 8% increase over the same period in 2018. This strong performance keeps us on track to reach our guided growth for the full year. We reported a GAAP net loss of $38.7 million for the second quarter of 2019. After adjusting for non-cash expenses and income tax, we reported a non-GAAP net loss of $24.5 million. On a gap basis, R&D expenses were $37.9 million for the second quarter of 2019. The increase over the same period in 2018 is largely attributable to higher expenses to support our clinical and product development efforts, including our three Phase III trials evaluating Fosnet Pantotenate and Sparsentine. On an adjusted basis, R&D expenses were $35.8 million for the second quarter.

This has allowed us to develop tailored best practices and drive engagement and protect and we're seeing that translate to strong enrollment trends.

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

Thank you Noah.

During the second quarter net product sales from our commercial portfolio grew to 44.7 million, an 8% increase over the same period in 2018.

This strong performance keeps us on track to reach our guidance growth for the full year.

We reported a GAAP net loss of 38.7 million for the second quarter of 2019.

After adjusting for non cash expenses and income taxes, we reported a non-GAAP net loss of 24.5 million.

On a GAAP basis, R&D expenses were $37.9 million for the second quarter of 2019.

The increase over the same period in 18 is largely attributable to higher expenses to support our clinical and product development efforts, including our three phase three trials evaluating firstnet panto today and for certain.

Eric Dube: Relevant non-cash expenses for the second quarter included $2.2 million of stock-based compensation and amortization. Selling General and Administrative Expenses for the quarter were $39 million. The increase over the same period in 2018 is largely attributable to headcount in support of our operational growth and increased professional fees. Professional fees during the quarter were materially higher due to legal fees pertaining to litigation and arbitration matters, including the settlement of all outstanding disputes between the company and its founding CEO, which was completed during the quarter. On an adjusted basis, non-GAAP SG&A expenses for the second quarter were $30.4 million. Significant non-cash adjustments for the quarter consisted of $8.6 million in stock-based compensation and depreciation and amortization. Our balance sheet remains strong. During the second quarter, roughly 23 million of our remaining 2019 convertible notes were converted to common shares outstanding.

On an adjusted basis R&D expenses were 35.8 million for the second quarter.

Relevant non cash expenses for the second quarter included 2.2 million of stock based compensation and amortization.

Selling general and administrative expenses for the quarter were 39 million.

The increase over the same period in 2018 is largely attributable to head count in support of our operational growth and increased professional fees.

Professional fees during the quarter were materially higher due to legal fees pertaining to litigation and arbitration matters, including the settlement of all outstanding disputes between the company and its founding CEO . It was completed during the quarter.

On an adjusted basis non-GAAP SG any expenses for the second quarter were 30.4 million.

Significant noncash adjustments for the quarter consisted of $8.6 million in stock based compensation and depreciation and amortization.

Our balance sheet remains strong.

During the second quarter, the roughly 23 million of our remaining 2019 convertible notes were converted to common shares outstanding.

Eric Dube: This leaves us with the $276 million in 2025 convertible notes that were issued last September. As of June 30, 2019, we have $425.9 million of cash and cash equivalents to support ongoing development efforts. For the remainder of 2019, we anticipate our R&D expenses may vary by quarter as a result of manufacturing clinical material and scaling for commercial readiness, but overall, we anticipate this resulting in a modest upward trend from current levels as we continue to advance our three Phase III programs throughout the year. Our base SG&A expense should return to the level seen in the first quarter, but there may be continued variability in professional fees throughout the balance of 2019. As a result of the recently announced decision on the CENSA-001 program, we anticipate an approximate $15 million write-off of the associated long-term investment during the third quarter. I now turn the call back to Eric for his closing remarks. Eric?

This leaves us with 276 million in 2025 convertible notes that were issued last September .

As of June Thirtyth 2019, we have 424 point 425.9 million of cash and cash equivalents to support ongoing development efforts.

For the remainder of 2019, we anticipate our R&D expenses may vary by quarter as a result of many flex manufacturing clinical material and scaling for commercial readiness, but overall, we anticipate this resulting in a modest upward trend from current levels as we continue to advance our three phase three programs throughout the year.

Our base SGN expense should return to levels seen in the first quarter, but there may be continued variability in professional fees throughout the balance of 2019.

As a result of the recently announced decision on the since the old one program, we anticipate an approximate $15 million write off of the associated long term investment during the third quarter.

Let me now turn the call back to Eric for his closing remarks, Eric.

Thank you Laura we made good progress in the first half of the year also continued to strengthen our organization.

Eric Dube: Thank you, Laura. We made good progress in the first half of the year and also continued to strengthen our organization. During the quarter, we were pleased to welcome Sandra Poole to our Board of Directors. Sandra joins us at a pivotal time and brings to the Board more than 25 years of biopharmaceutical product development and manufacturing experience that will be invaluable as we further our mission of delivering life-changing therapies to people living with rare diseases. For the balance of 2019, our priority will be to focus on execution. We are looking forward to the upcoming data readout from our Phase 3-4 study later in the quarter, which, if successful, would support NDA and MAA submissions to potentially make Fosnit-Pantotenate the first approved treatment for PCAN.

During the quarter, we were pleased to welcome Sandra pool to our board of directors Sandra joins us at a pivotal time and brings to the board more than 25 years of biopharmaceutical product development and manufacturing experience that will be invaluable as we further our mission to develop to delivering life changing therapies to people living with rare disease.

For the balance of 2019, our priority will be to focus on execution.

We are looking forward to the upcoming data readout from our phase three fourth study later in the quarter, which if successful would support and da and M&A submission to potentially make fossett penta Nate the first approved treatment for Pete can.

Eric Dube: Beyond our FOSMED Pantotenate Program, we are focused on executing and accelerating enrollment in our two pivotal studies that have the potential to make Sfarsentin the new treatment standard for FSGS and IGA nephropathy. And with the recent approval of PHYO-EC, we are focused on achieving a successful launch to continue the growth of the franchise that has become this treatment of choice for patients with Cystinuria. Let me now turn the call back over to Chris to open it up for questions.

Beyond our fog that tend to it in a program we are focused on executing and accelerating enrollment in our two pivotal studies that have the potential to makes more sense and the new treatment standard for Fscs and hygiene and prophecy.

And with the recent approval of final you see we are focused on achieving a successful launch to continue the growth of the franchise that has become the treatment of choice for patients with Cystinuria, Let me now turn the call back over to Chris to open it up for questions Chris.

Unknown Executive: Great. Thanks, Eric. Rusty, can we go ahead and open up the lines for Q&A, please? Cheers, ladies and gentlemen, if you have questions at this time, press the star on the number one [inaudible] First question comes from the line of Maurice Raycroft. Hi, everyone. Good afternoon, and thanks for taking my questions. My first question is for Noah.

Great. Thank their resi can we go ahead and open the line for Q and a please.

Sure sure and ladies and gentlemen, if you have questions at this time.

Simply press Star then number one.

Again its follow on.

Question.

Our first question comes from the line of Marine reach off from Jefferies. Your line is open.

Hi, everyone. Good afternoon, and thanks for taking my questions.

First question.

Unknown Executive: So you mentioned the acceleration of activities at registries as one example of an initiative taken to enhance enrollment in FSGS. Just wondering if you can comment on any of the other initiatives that were made to potentially enhance enrollment. Yeah, thanks for a great question.

His for Noah.

So you mentioned the acceleration of activities at our registries is one example of an initiative taken to enhance enrollment in Fscs. Just wondering if you can comment on any of the other initiatives that were.

That were made to potentially enhance enrollment.

Yes, Thanks for a great question first let me say that.

Noah: First, let me say that, you know, regarding the delay in enrollment, we are confident in our new timelines and very pleased with the conduct of the study to date. The main thing that we focus on is ensuring a high-quality study. And as you know, enrollment in these types of clinical trials continues to pick up as you open more sites and begin to gain traction. You know, Duplex is doing that. The challenge is that the rate of acceleration was not as fast as we expected it to be in the early summer months, which caused a shift in our timelines. And I just want to give a lot of credit to our team for recognizing this and pulling these planned tactics forward.

You know regarding the delay in enrollment we are confident our new timelines.

Have you been very pleased with the conduct of the study to date. So the main thing that we focus on is ensuring a high quality study and as you know enrollment in these types of clinical trials continue to pick up as you open more sites and begin to gain traction duplexes doing that the challenges the rate of acceleration was not as fast as we expected to be in the early summer months, which caused a shift for our timelines and I just want to give a lot of credit to our team for recognizing this and pulling these planned tactics forward.

Our leadership to get to your question in Fscs built through the duet study has allowed us to leverage key relationships with registries and pathology groups to build.

Noah: Our leadership, to get to your question, in FSGS, built through the DUET study has allowed us to leverage key relationships with registries and pathology to build and drive patient identification outside of the key academic centers and centers of excellence. So, you know, I just want to reemphasize that, you know, we found in our DUET work that being able to reach these sort of geographic foundational databases can have a significant, meaningful impact on enrollment, and we're starting to see that. I got it. Can you provide any granularity into what you're seeing at sites? Are there some sites that may be underperforming, and you may have to add additional, more sites than anticipated originally?

And drive patient identification outside of the key academic centers and the centers of excellence. So yes, I just want to reemphasize that we found in our duet.

Work that being able to reach these sort of of geographic foundational databases can have a significant meaningful impact on enrollment and we're starting to see that.

Got it can you provide any granularity into what you are seeing AD side, sorry are there. Some site did maybe underperforming you may have to.

Add additional.

More sites in it than anticipated originally.

Eric Dube: Yeah, Maury, let me comment. This is Eric.

Yeah more let me let me comment this is Eric.

Eric Dube: You know, just based on what Noah mentioned, we're really pleased with the conduct of both of the studies in terms of the site engagement, the number, and the type of patients that we're receiving into the study. And so I think that there's not anything that would be concerning there. I think one of the things, if we take a step back, you know, that we continue to see as the leader within the rare glomerular space, nephrology was one of the therapy areas that had the lowest clinical trial activity over the last few decades. And glomerular disease was the lowest among kidney diseases. And so, you know, we have to really make sure that we're building that foundation of not just the few hundred academic sites, but how do we link those academic and clinical trial sites to the broader network of over 8,500 regional and community nephrology centers in the U.S., and so I think what Noah mentioned in a lot of the tactics that we have been focusing on and increasing is really building that connectivity. And I think what a registry does is to help build that connectivity between the sites that we have ongoing, the sites that we have planned, and to make sure that we continue to build this capability within the nephrology clinical trial area.

Just based on the what Noah mentioned, we're really pleased with the conduct of both of the studies in terms of the site engagement the number and the type of patients that were receiving into the study and so I think that there is not.

Anything that would be concerning there I think one of the things if we take a step back.

That we've continued to see as the leader within the rare glum area of space Nephrology was one of the therapy areas that had the lowest clinical trial activity over the last two decades in gloom aerial or disease was the lowest among nephrology and so we have to really make sure that we're building that foundation of not just the few hundred academic sites, but how do we link those academic and clinical trial sites to the broader in the us over 8500.

Regional and community Nephrology centers, where the majority of patients are seen and so I think what Noah mentioned in a lot of the tactics that we have been focusing on an increasing is really building that productivity and I think what a registry does is to help build that connectivity into the site that we have ongoing the sites that we have planned.

And to make sure that we continue to build this capability within the nephrology clinical trial area.

Eric Dube: Got it. That's really helpful.

Got it Thats really helpful and then.

Eric Dube: And then just a question on Thiola. You mentioned that some of the patients who discontinued Thiola at one point could potentially come back to the drug for the new formulation. So I'm just wondering if you can provide any specifics as to why the patients would have discontinued in the first place and if they would primarily be coming back for the lower pill burden or what else you can say about that. And then if the new formulation could help support your conversation with USPTO for potentially a patent approval there.

Just a question on Thiola.

So you mentioned that some of the patients.

Who have discontinued style at one point could potentially come back to the drug for the new formulation. So I'm. Just wondering if you can provide any specifics as to why the patients would have discontinued in the first place and if they would primarily be coming back for the lower pill burden or what else you can say about that and then if the new formulation. If if that could help support your conversation with you guys speak for.

Potentially patent approval there.

Eric Dube: Yeah, so let me first start with, you know, what we're seeing in terms of the potential and the types of patients. I'd say, first of all, it's early in the launch, so I wouldn't be able to provide any specific details on what we're seeing.

Yes, So let me let me first start with what we're seeing in terms of the potential and the types of patients I'd say first of all it's early and lost so I wouldn't be able to provide any specific details on.

What we're seeing other than we're seeing a very positive response from physicians and patients we knew going in through the development over the last couple of years that there would be a significant demand for this.

Eric Dube: Other than, you know, we're seeing a very positive response from physicians and patients. We knew going in through the development over the last couple of years that there would be a significant demand for this formulation, just based on the challenges that we've heard from patients. And the profile of Fiola AC was very much informed by prior and current Fiola patients. And so, you know, our focus is to make sure that we continue to build awareness and education around Cystinuria and the potential treatment options. And really, there are three areas of focus that we have for the uptake of Viola-EC. The first is, of course, to continue to drive new patients and their physicians to therapy and to allow them to think about Viola-EC as a choice for them because of its profile. The second is to work with current patients that may see this choice for them given the different aspects of food or without food and the pill burden.

Formulation just based on the challenges that we've heard from patients in the profile of bio is C was very much informed by prior and current.

File to patients.

And so our focus is to make sure that we continue to build awareness and education around cystinuria and the potential treatment options and really there are three areas of focus that we have for the uptake of bio SC. The first is of course to continue to drive new patients.

And their physicians to therapy and to.

Allow them to think about file that you see of the choice for them because of the profile. The second is to work with current patients that may see this choice for them given the different aspects of food or without food and the and the pill burden.

Eric Dube: And with regard to your question around reengaging patients who've stopped therapy for a number of reasons, we want to make sure that they reengage with therapy and whether Viola-EC or Viola is the right choice for them. We know that for some patients, those are the reasons why they stopped. We also know that it may just be that, you know, patients stop taking the medicine for a whole host of reasons. But most importantly, we want to make sure that these patients are on therapy and that their therapy is optimized. And that's very much our goal and why we talk about not putting any barriers up for these patients. And I think we're confident in the outlook of being able to continue the growth of this franchise, just based on those, but particularly in re-engaging patients.

And with regard to your question around Reengaging patients, who stopped therapy for a number of reasons.

We want to make sure that they reengage with therapy, and whether file that you see or feel is the right choice for them. We know that for some patients. Those are the reasons why they discontinued. We also know that it may just be that patient discontinue for a whole host of reasons.

But most importantly, we want to make sure that these patients are on therapy and that their therapy is optimized and thats very much our goal and why we talk about not putting any barriers up for for these patients.

And I think we're confident in the outlook of being able to continue the growth of.

Of this franchise just based on on those but particularly in Reengaging patients and I'm pleased to say that we have shipped a number of prescriptions to patients fortify O E C, including a number of patients who stopped therapy as far back as 2017, and so we're really pleased to see as we would have expected from market research that.

Eric Dube: And I'm pleased to say that we have shipped a number of prescriptions to patients for thiola EC, including a number of patients who stopped therapy, you know, as far back as 2017. And so we're really pleased to see, as we would have expected from market research, that thiola EC is meeting a need for these patients. Now, with regard to your question about patents, we have mentioned that there has been a patent that was filed with the U.S. Patent Office. That patent is pending, it's undergoing review, and as you know, those review periods are iterative. We can't really say whether and when we would receive any type of coverage for file EEC, and so our focus remains ensuring access and supporting education for the cyst and urea community and to bring file EEC as another choice for these patients.

That file is the meeting.

Need for these patients.

Now with regard to your question about.

Patent we have mentioned that there has been a patent that was filed with the US patent office that is pending its undergoing review and as you know those review periods are.

Our iterative, we can't really say, whether and when we would receive.

Any type of coverage profile that you see and so our focus remains ensuring access and.

To support education for the cystinuria community and to bring so what you see is another choice for for these patients.

Maurice Thomas Raycroft: Got it. That's very helpful. Thank you very much. And I'll hop back in the queue.

Got it Thats very helpful. Thank you very much and I'll hop back in the queue.

Unknown Executive: Thanks, Mark.

Thanks Mark.

Rusty can we go and go to the next question. Please.

Michelle Gilson: Rasty, can we go ahead and go to the next question, please? Our next question comes from the line of Michelle Gilson from Canada Co-Originity. Your line is open. Hi, thank you for taking my question. I was just wondering if you could tell us a little bit more about what kinds of analyses are planned around the phase three and four results and what we should be expecting from a top line release. And then I think they've talked in the past about looking at the different subdomains of the PECAN ADL score; are there certain domains that you view as more important from a regulatory or commercial perspective?

Sure Sir our next question comes from the line of Michelle Gilson from Canaccord Genuity. Your line is open.

Hi, Thank you for taking my question.

I was just wondering if you could talk a little bit more about what kinds of analyses are planned around the phase three for results and.

What we should be expecting from a topline release.

And then I think we've talked.

In the past about looking at at the different sub domains of the P. can E.D.L. score or are there certain domains that you view as more important from a regulatory or commercial perspective.

Eric Dube: Thanks, Michelle. This is Eric.

Eric Dube: Let me start, and I'll ask Noah to provide a little bit more detail. I think first and foremost, our analysis priority is very much around the primary endpoint of PKEN-ADL, as well as safety and tolerability during the 24-week double-blind period. And our data release, as we've mentioned, will be sometime this quarter, so it is certainly near term. We also are looking at a couple of conferences, depending on the timing and acceptance of those abstracts, including MDS, which is in September, and then there's another conference in October, if for some reason we're not able to meet that. I think with regard to the areas, I'll first start with what I've heard from that conference. I mentioned publications that really focus on the experience of patients and families with PCAN.

Thanks, Michelle This is Eric let me, let me start and I'll ask no it to provide a little bit more detail I think first and foremost our analysis. Our priority is very much around the primary endpoint of pecan HDL as well as the safety and Tolerability for the 24 week double blind period, and our data release as as Weve mentioned will be sometime this quarter. So it is it is certainly a near term. We also are looking at a couple of conferences, depending on the timing and acceptance of those abstracts, including India, which is in September and then there's another conference in October if for some reason were not able to meet that I think with regard to the domains. All first start with what I've heard from that conference I mentioned in my early comments as well as some.

Publications that really focus on the experience of patients and families with P. Ken.

Eric Dube: You know, some of the most debilitating symptoms that these patients face are often the first symptoms that emerge, such as speech, writing, and walking difficulties. And I think what we see and understand from some of these patients is that these are the symptoms that are oftentimes most debilitating or make it very difficult to stay connected or communicate between patients and their families or caregivers, or that require much more caregiving, knowing that the majority of patients with PCAN require part- or full-time caregiving. I think that's really what we're thinking about in terms of what we hope to see in these. And you know, our focus is ensuring, as we run the study, to see at least a three-point difference versus placebo over the double-blind period, which we believe would likely then reflect improvements in more than one of those domains. Noah, I'd like to turn it over to you to see if there are any additional analyses or comments that you'd like to provide.

Some of the most debilitating symptoms that these patients face are often times the first symptoms that emerge.

Such as speech, writing and walking difficulties and I think what we see and understand from some of these patients is that these are the symptoms that are oftentimes, most debilitating or make it very difficult to stay connected or communicate between patients and their families or caregivers or that require much more caregiving, knowing that the majority of patients with PK and require a part or full time care, giving.

I think that's really what we're thinking about in terms of what we hope to see.

In the <unk> and.

Our focus is ensuring as we powered the study to see at least a three point difference versus placebo over the double blind period, which we believe would likely then reflect improvements in more than one of those domains.

No I'd like to turn it over to you see if theres any additional analyses are committed to provide sure. Erik I think you provided quite a bit of death or but I'll just add a couple of things I think Michelle you asked about sub analyses are subgroup analysis, just to kind of highlight I mean, clearly one of the important populations with pediatric about a third populations, we revealed or pediatric patients.

Noah: Sure, Eric, I think you provided quite a bit of depth there, but I'll just add a couple things. I think, Michelle, you asked about sub-analyses or subgroup analysis, just to kind of highlight, I mean, clearly, one of the important populations is pediatric. About a third of the populations we revealed are pediatric patients. You know, important to see what the effect would be there. There's also a classic versus atypical presentation of the disease. For example, look at age of onset.

Important to see what the effect would be there. There is also a classic versus a typical presentation of the disease I'm look at age of onset you're fairly traditional risk factors that are seen in these PK studies, but it is really important to get those groups and understand the progression. There is some heterogeneity as you know and progression of disease. So we've already got plans in place to analyze those populations.

Noah: You know, you've got fairly traditional risk factors that are seen in these PCAN studies, but it's really important to get those groups and understand the progression. There is some heterogeneity, as you know, and progression of disease. So we've already got plans in place to analyze those populations.

Noah: And then as far as regulatory domains are concerned, I'll just touch upon what Eric said. You know, we've got a three-point change agreed upon with the SPA and with FDA. I mean, that really covers the waterfront, mainly for us.

And then as far as.

Regulatory domains I'll, just touch upon what Eric said.

We've got a three point change agreed upon with the Spa with FDA I mean, not really covers the waterfront mainly for us and some of the domains. Eric mentioned are really key couple of others think about to our swallowing and walking I always look at those because theres disease modification potential their patient can't swallow that could have potentially pneumonia aspiration pneumonia be hospitalized death.

Noah: And some of the domains that Eric mentioned are really key. A couple of others to think about, too, are swallowing and walking. Always look at those because there's disease modification potential there. Patients can't swallow. They can potentially get pneumonia, aspiration pneumonia, be hospitalized, and die.

Noah: You know, obviously, we're not going to show that in six months, but there is, or we might, but it's unlikely. But these are the kinds of things we want to follow up on and make sure and look carefully at because they also have compelling reasons. And finally, the last thing I'll say is, even just, when Eric and I talk to patients' families, even just the ability to be more independent, ability to give the patient caregiver a little bit of a break, being able to dress themselves, speech, better articulation, these are really important to patients. And again, back to the PK and ADL scale, it was designed by patients, caregivers, and physicians so that even a one Okay, and then can you talk a little bit about what you're doing to prepare for launch in terms of patient identification efforts? And, you know, you've talked a lot about the worldwide population for PQM as well. So how are you thinking about access in the rest of the world outside the U.S.?

Obviously, we're not going to show that in six months, but there are we might but unlikely but these are the kinds of things we want to follow up and make sure and and look carefully because they also have a compelling returns and finally the last thing I will say is even just we put when Eric and I talked to patients families. Even his ability to be more independent ability gives the patient caregiver a little bit of a break being able to dress themselves of speech as art better articulation. These are really important to patients and again back to the peak in HDL scale. It was designed by patients caregivers and.

Positions. So that has been a one point change on any of those domains would have a clinical meaningfulness.

For them.

Okay.

And then can you talk a little bit about what you're doing to prepare for launch in terms of patient identification.

Birds and John .

In you you talked a lot about worldwide population for PJM as well, so how you're thinking about access and the rest of the world outside the U.S.

Eric Dube: Yeah, thank you, Michelle. So certainly, we are focusing our efforts first on the U.S. and Europe, where many of these patients are and have been linked to care. Some of our efforts are to identify the number of patients in those Centers of Excellence or with specialty centers that have looked to engage in clinical trials or have been, you know, seen by those clinicians.

Yes. Thank you Michel so certainly we are focusing our efforts first on the us and Europe , where many of these patients are and have been linked to care. Some of our efforts is to identify the number of patients in those centers of excellence.

Order with specialty centers that have looked to engage in clinical trials or have been.

As seen by those clinicians and we've we've mentioned previously that there are over 400 patients that have been identified through those efforts and that's in the context of what the literature says of about 5000 patients worldwide.

Eric Dube: We've mentioned previously that there are over 400 patients that have been identified through those efforts. And that's in the context of, you know, what the literature says about 5,000 patients worldwide.

Eric Dube: What we're doing currently is to refine some of the epidemiology in this space to make sure that we really understand the number of patients and where they are country by country. We are also making sure that we identify who the treating clinicians are and what the experience and patient journey is to diagnosis. We know in rare diseases, and particularly with an ultra-rare disease, that oftentimes the biggest challenge in identifying patients is the number of years it takes between the symptom onset and proper diagnosis. And so we want to make sure that we can close that gap. And that's really by understanding the patient journey. I think we've really made some good progress on that front. And part of what we're also trying to do is make sure that we have the team in place in those key roles that I mentioned before so that we can move very quickly once we do gain approval.

What we're what we're doing currently is to refine some of the epidemiology in this space to make sure that we really understand.

Where the the number of patients and where they are country by country.

We also are making sure that we identified.

Who the treating clinicians are and what the.

The experience and this patient journey is to diagnosis, we know in rare disease, and particularly with an ultra rare disease that oftentimes the biggest challenge in identifying patients isn't in.

Isn't.

The number of years it takes between the symptom onset and proper diagnosis and so we want to make sure that we can close that gap and Thats really valley understanding that patient journey I think we've really made some good progress on that front and part of part of what we're also trying to do is make sure that we have the team in place in those key roles that I mentioned before so that we can move very quickly once we do gain approval.

Okay. Thank you.

Michelle Gilson: Okay, thank you. Thanks, Michelle.

Thanks Michelle.

So.

Our next question comes from the line of team Lugo from William Blair. Your line is open.

Timothy Francis Lugo: Our next question comes from Tim Lugo from William Blair on the line of, Thanks for taking the question. Going back to the FIALA EC, can you maybe provide some quantification about how much growth you think this could lead to the base business? Also, you know, some of the numbers of patients who have tried the legacy formulation and discontinued, and maybe how long you expect to convert current form or prior formulation patients on to EC.

Hi, Thanks for taking the question going back to the sale that you see can you maybe provide some clarification about how much growth you think this could lead to the base business.

Also you know some of the numbers of patients who have tried the legacy formulation and discontinued.

And maybe how long you expect to convert current or prior formulation patients onto you see.

Yeah. Thanks.

Eric Dube: Yeah, thanks Tim for the question. So we do expect the market to continue to grow for the foreseeable future, especially with the introduction of the new treatment options in Psyol-EC. Cystinuria, like so many other rare diseases, has been underserved despite having therapies available. And that's why increasing access, awareness, and education has been a central focus of ours.

And that's why increasing access awareness and education has been a central focus of ours and since acquiring the rights to COO.

Eric Dube: And since acquiring the rights to thiola five years ago, we've seen the number of patients being treated with thiola increase from about 400 to more than 1,200. And to answer your question about the number of patients, we've seen that the total number of patients, there are about 30% of those that, over that period of time, have discontinued therapy. And we know that even, you know, beyond that, the majority of cystineuria patients are still untreated. And that's despite Biola's utility as the treatment of choice.

Five years ago, we've seen the number of patients being treated with file increase from about 400 to more than 1200 and to answer your question around.

The number of patients we have seen that the total number of patients who is about 30% of those that over that period of time have discontinued therapy.

And we know that even beyond that that the majority of cystinuria patients are still on treated and thats. Despite filed as utility as the treatment of choice and there are many challenges for these patients to overcome.

Eric Dube: And there are many challenges for these patients to overcome, not just with diagnosis, but with the existing formulations that have led those patients to discontinue treatment. Our goal is to continue our commitment to this community through making Thiol ADC available, which addresses a number of those challenges. And by furthering our education and awareness efforts about the treatment options available. We also want to make sure that once a patient is treated, they're optimally treated, so that we have an opportunity to build upon our work with the Cystinuria community and provide patients with a choice for their treatment. Whether or not at some point there's a generic, I really can't say.

Not just with diagnosis, both with the existing formulation that have led those patients to discontinue treatment. Our goal is to continue our commitment to this community through making Cy only see available which addresses a number of those challenges and by furthering our education and awareness efforts about the treatment options available.

And we also want to make sure that once the patient is treated that theyre optimally treated so that we have an opportunity to build upon our work with the cystinuria community and provide patients with a choice for their treatment whether at some point theres a generic I really cant say and we have a policy to provide samples to bonafide requesters and we're in the process of providing file with samples during the third quarter.

Eric Dube: And we have a policy to provide samples to bona fide requesters, and we're in the process of providing thiola samples during the third quarter. What I will say in terms of future growth is that we remain focused on our commitment to education and access and bringing the new treatment option of thiol-EC to patients to help address some of the challenges we know that they've lived with over the years. And as a result of this, we're confident in the potential for thiol-EC uptake and the number of treated patients to continue to grow for the foreseeable future. So I think, you know, all in all, it reinforces what we heard early on about the challenges of this disease and this treatment, and we're optimistic about the early signs of this launch.

What I will say in terms of the future growth is that we remain focused in our commitment to education and access and bringing the new treatment option of file that you see the patients to help address some of the challenges we know that they've lived with over the years and as a result of this we're confident in the potential for bio HPC uptake and the number of treatment treated patients to continue to grow for the foreseeable future. So I think all in all it reinforces what we heard early on about the challenges of.

This disease and the treatment and we're optimistic in the early signs of this launch.

Thank you for that.

Eric Dube: Thank you for the thank you for the thorough answer. Maybe if I could squeeze one more in on pecan.

Okay. Thank you for the simple answer.

Maybe if I could squeeze one more in.

Pete can you remind me.

Timothy Francis Lugo: Can you remind me, perhaps Noah, can you remind me what the expectations are for the placebo response in the study? Yeah, that's a great question, Tim. So, if you recall, we don't expect a meaningful change in the placebo arm over the six-month or 24-week period. You know, while the natural history in PECAN is limited, we do know from our research and interactions over the years that this disease has not typically been characterized by what I would call spontaneous improvement. You know, these are pretty sick debilitated patients. They're expected to decline, you know, but at varying rates depending on the disease presentation. So, you know, when you think about that in the context of a placebo effect, you know, while there is some work in Parkinson's and you can see some improvement on these types of scales, the UPDRS, there's usually a low improvement given how severe these patients are. It's pretty unlikely that it would be sustained.

Snow can you can you remind me what the expectations are for placebo response in this study.

Yeah, that's a great question Tim so.

If you recall, we don't expect a meaningful change in the placebo arm.

Over the six month 24 week period.

Well the natural history and Pecan is limited we do know from our research interactions over the years disease has not been typically characterized by whatever call spontaneous improvement. So these are pretty sick debilitated patients they are expected to decline.

No, but at varying rates, depending on disease presentation. So we think about that in the context of placebo effect.

While there is some work in Parkinsons and you could see some improvement on these types of skills Pdrs was usually low improvement given how severe these patients are it's pretty unlikely that will be sustained.

Noah: And I just want to emphasize, you know, there was a recent study in this population where the placebo arm declined 2 to 3 points on UPDRS Part 2 over 18 months. So, I think that supports that thesis. And, you know, the most important part, you know, Tim, as we look at this study on a blinded basis, we're really seeing overall variability within our empowering sum.

And I just want to emphasize if there was a recent study another study in this population a placebo arm declined two to three points on eurosport to over 18 months. So I think that supports that thesis and the most important part Tim as we look at the study on a blinded basis, we're really seeing overall variability within our powering assumptions hope that helps answer the question.

Noah: Hope that helps answer the question. Very helpful, and we're looking forward to the results. Thanks for the answer. Awesome. Thanks, Tim. Our next question comes from the line of Joseph Schwartz from SVB Lyrinc. Your line is open. Thanks very much.

Very helpful. We're looking forward to the results thanks for the answers.

Awesome Thanks to.

Our next question comes from the line of Joseph Schwartz from SVB unique.

Your line is open.

Thank you very much.

Joseph Patrick Schwartz: So I was wondering if you could give us any more insight into when the fourth data will be announced in the third quarter. I heard you mention a couple meetings, one of which is actually just in the fourth quarter. Do you think that if the data were not accepted at the meeting in September, the data might slip into the fourth quarter? Or, in any event, do you think we might, should we expect a press release for the top-line data in advance of a medical meeting?

So I was wondering if you can you give us any more insight into when in the third quarter, we should expect the for data to be.

Announced I heard you mentioned a couple meetings, one of which is actually just in the fourth quarter.

Do you think that if that if the data were not accepted that the meeting in September there with it.

The data might slip into the fourth quarter or in any event do you think we might.

Should we expect a press release.

For the top line data in advance of a medical meeting.

Eric Dube: Yeah, thank you, Joe. So, with regard to specific timing, you know, we haven't mentioned anything beyond the third quarter. And I will tell you that once we unblind the data, we'll work very quickly to have an announcement, you know, a press release. And we want to make sure, given the high unmet need and the real hope for a therapy here, that we're going to very quickly work on getting the more complete communication within the medical space that we're going to have with the conference and then, obviously, a peer-reviewed journal. Certainly, you'll hear from us, you know, very shortly after we unblind the top line, and that will be in the third quarter.

Yes. Thank you Joe So I'd say with regard to specific timing, we haven't mentioned anything beyond third quarter and I will tell you that once we unblind. The data will work very quickly to have an announcement press release, and we want to make sure given the high unmet need and the real hope for a therapy here that we're going to very quickly work on getting a more complete communication within the.

The medical space, the culprit for that and obviously a peer reviewed journal.

Certainly you'll hear from us very shortly after we unblind the topline and that will be in the third quarter.

Okay. Good luck.

Eric Dube: Okay, good luck. And then given your plans to establish a commercial footprint for addressing PECAN outside the U.S. and what you know about cystinuria from your work with Theola inside the U.S., I was wondering, now that Theola EC has been FDA approved, do you have any thoughts on maybe bringing that outside the U.S. in order to leverage your footprint if, hopefully, you're able to use it for PECAN?

And then given your plans to establish commercial footprint.

For.

Addressing pecan outside the us and what you know about cystinuria from your work with feel that inside the U.S. I was wondering now that you feel like you see has been an FDA approved do you have any thoughts on maybe bringing that outside the U.S.

In order to leverage your your footprint and hopefully you are able to use it for for Beacon.

Eric Dube: Yeah, it's a great question, Joe. I mean, certainly we're looking at how do we how do we have a, first and foremost, an effective model outside of the US. And, you know, having worked outside of the US, we have to really think about what's right for that region. What would work in the US isn't going to work in every country in Europe. But what we want to make sure that we can do is work in the right centers, make sure that we have, you know, a distribution model that is able to effectively reach these patients. And, you know, we'll look at whether, you know, some of our current portfolio or, you know, through our business development activities, things to be able to leverage the infrastructure that we're building, you know, much like we have within the US. And I think, you know, the launch of FOSMET outside of the US really will be the foundation for future growth for this company.

Yes, a great question, Joe I mean, certainly we're looking at how do we how do we have a.

First and foremost to an effective.

Model outside of the U.S. and having worked outside of the U.S.. We have to really think about what's right for that region. What would work in the U.S. is not going to work in every country in Europe .

But we want what we want to make sure that we can do with his work in the REIT centers make sure that we have.

You know a distribution model that is that is able to effectively reach these patient and we'll look at whether you know some of our current portfolio or you know through our business development activities things to be able to leverage the infrastructure that we're building.

Much like we have within within the U.S. and I think the launch of a pause that outside of the U.S. really will be the foundation for future growth for this company.

Great. Thank you.

Christopher Moriah: Great, thank you. This question comes from the line of Christopher Moriah from NORA. Hey, good afternoon.

Our next question comes from the line of Christopher Marai from Nomura. Your line is open.

Hey, good afternoon, thanks for taking the question.

Eric Dube: Thanks for taking the question. Just maybe regarding your decision on the PKU program, I was wondering if you could elaborate a little bit more if that was based on sort of the competitive landscape emerging there, you know, or data very specifically. So, you know, was it one or the other? Or perhaps could you comment on any others? You know, perhaps data that you're seeing, like increased confidence out of the four trial blinded data that had you, you know, helped make you helped you make that decision. And then I've got a follow up.

Just maybe regarding your decision on the T.K. you program I was wondering if you could elaborate a little bit more of that was based on sort of the competitive landscape emerging there or data very specifically, so what was it one or the other.

Or perhaps could you comment on any other.

Perhaps stated that you are seeing like increased confidence out of the four trial blinded data that had had you you know.

Helped to make you hoped.

It helps you make that decision and then I've got a follow up.

Eric Dube: Sure, yeah, Chris, thanks for the questions. I mean, first, let me start with the last question, which is around Fort and whether we have greater confidence. I'd say we have confidence in the Fort study. That study remains blinded, and we made the decision around SINSA to be independent and mutually exclusive. We want to make sure that we're very disciplined in each of our programs and company decisions.

Sure Yeah, Chris Thanks for the questions I mean first let me start with the last question, which is around four and you know is it that we have greater confidence I'd say, we have confidence in the fourth study that study remains blinded and we made the decision around since <unk> independent and a mutually exclusive we want to make sure that we're very disciplined in each of our programs and company decision with regard to the sensor program I want to remind you and everyone that this was a joint development program with sensor pharmaceuticals, and so we really are not in a position to disclose or comments on on the data that you know and so what I would say its despite approved treatments in T.K.U.. We recognize that there continues to be an unmet need in T.K. You. Unfortunately were not in a position you know really to go into a level of detail on our assessment for the data since we don't own the program.

Eric Dube: With regard to the CENSA program, I want to remind you and everyone that this was a joint development program with CENSA Pharmaceuticals, and so we are really not in a position to disclose or comment on the data. And so, what I would say is, despite approved treatments in PKU, we recognize that there continues to be an unmet need in PKU. Unfortunately, we're not in a position, you know, really to go into a level of detail on our assessment of the data since we don't own the program. And while there may be potential for CNSA 001 to ultimately become a treatment option, it didn't meet our requirements for moving forward with the acquisition of SENSA pharmaceuticals. And so I just wanna make sure that, you know, we recognize that we're just not gonna be able to disclose any of the data that we've seen. That's really the decision for SENSA to make.

And while there may be potential for CNS, eight 001 to ultimately become a treatment option.

It Didnt meet our requirements for moving forward with the acquisition offensive pharmaceuticals, and so I just want to make sure that you know we we recognize that we're just not going to be able to disclose any of the data that we've seen that's really the decision for sensor Tonight.

Got it and then maybe just with respect to the Ford study and the open label extension you had highlighted there are some patients could have been on drug for about two years, that's well past via the primary endpoint.

Eric Dube: And then maybe just with respect to the Ford study and the open label extension, you know, you highlighted there are some patients that have been on the drug for about two years. That's well past the primary end point of the study. I was wondering if you had any anecdotes of benefit that you could share or, secondarily, perhaps any details on compliance. I guess, you know, the pill burden three times daily, that kind of thing, you know, could be. You know, something that would be of interest. Thanks.

You know the study I was wondering if you had any anecdotes as benefit that you could share or secondarily, perhaps any details on compliance I guess, you know till Gilbert and three times daily that kind of thing you know could could be.

You know something that would be of interest.

Thanks.

Yeah. Thank you, Chris let me say that we are not going to be in a position to be able to talk about any anecdotes I mean, the study remains blinded and we want to make sure that we respect that blind, including you know the the patients in an open label extension I will remind everyone that you know the the real objectives of the open label extension. You know are really twofold first and foremost to be able to gather longer term safety and efficacy data in the treatment of a false met and secondly to be able to assess those patients who received placebo in the double blind period, but then switched after 24 weeks to.

Eric Dube: Yeah, thank you, Chris. But let me say that we are not going to be in a position to be able to talk about any anecdotes. I mean, the study remains blinded, and we want to make sure that we respect that blind, including, you know, the patient in the open-label extension. I will remind everyone that, you know, the real objectives of the open-label extension are really twofold. First and foremost, to be able to gather longer-term safety and efficacy data in the treatment of FOSMET, and secondly, to be able to assess those patients who received placebo in the double-blind period but then switched after 24 weeks to active treatment. And so, you know, we'll certainly look to explore that, but first and foremost, our priority remains a high-quality analysis and readout of the double-blind period.

Active treatment and so you know, we'll certainly look to explore that but first and foremost our priority remains on high quality analysis and read out of the of the double blind period. So you know I think you know, we'll we'll save the anecdotes for later our focus remains on on that analysis of a topline. So the other thing that I will say is that you know with regard to the overall study the drop out rate remains low and all patients that completed that double blind period have switched over whether we can confirm or anything around compliance overdone et cetera. I. You know I think that remains to be seen that certainly will be something we look at.

Eric Dube: So, you know, I think, you know, we'll save the anecdotes for later. Our focus remains on that analysis of the top line. The other thing that I will say is that, you know, with regard to the overall study, the dropout rate remains low, and all patients that completed that double-blind period have switched over. Whether we can conclude anything about compliance, pill burden, et cetera, you know, I think that remains to be seen. That certainly will be something we look at. But I think it's encouraging that we will have a robust data set to be able to support a high-quality analysis of this study.

But I think it's encouraging that we will have a robust data set to be able to support the high quality analysis of the study.

Eric Dube: Got it. And then maybe just one last one, kind of a two-parter.

Got it and then just maybe one last one kind of a two parter on the FDA and EMEA you expect to file at the same same time, roughly and then would you be looking at you partner and then maybe tying that into an earlier question you know given your non opting into the incentive program.

Eric Dube: The NDA and MMA, do you expect to file at the same time, roughly? And then, maybe tying that into an earlier question, you know, given you're not opting into the SENSEP program, how do you look at potential other assets to license or acquire? Maybe if you could explain some of your thought process around that potential. Thank you.

Yeah, how do you look at potential other license.

Ethics to 10 licensing or acquire maybe if you could explain some of your thought process around around that potential. Thank you sorry, yep. Thanks, Chris.

Eric Dube: Okay, so first, with regard to the NDA and MAA submission, we want to make sure that those are submitted as close to each other as possible. They won't be simultaneous, but certainly they will be close, and I think we'll be in a better position to provide timing after the data readout, etc.

Okay. So first with regard to the N. DJ and M. A submission we want to make sure that those are submitted as as close as possible they won't be simultaneous but certainly they will be they will be closed and I think we'll be in a better position to provide timing after the the data readout et cetera.

Eric Dube: With regard to our commercial model or go-to-market model in Europe and a potential partner, this is one where I believe that we will be able to do this on our own. We have an understanding of what it takes for rare diseases and a lot of the focus that we have with regard to identifying patients and having strong relationships with centers of excellence and their referral patterns, and we believe that the opportunity for PCAN is reasonable enough for us to start that approach of building that operating model in Europe. Certainly, we will have partners with regard to market access and distribution, etc., but really, the overall model will be owned and driven by Ritrofen. And then your final question around business development, you know, as we look at what's in front of us, both the completion of the joint development agreement with CENSA and then the completion of the phase three program with FOSMET in PKU, we do want to make sure that we fill our pipeline.

With regard to our commercial model or go to market model in Europe and at a potential partner.

This is one where I believe that we will be able to do this on our own you know we have the understanding of what it takes in rare disease and a lot of the focus that we have with regard to identifying patients having strong relationships with the centers of excellence in their referral patterns.

We believe that the opportunity for for Pecan is reasonable enough for us to to start that that approach of building that operating model in Europe , certainly we will have partners with regard to market access and distribution etcetera, but really the overall model will be will be owned and driven by by Retrophin.

And then your final question around business development, you know as we look at the you know what's in front of US both to the completion of the joint development agreement with FEMSA and then the completion of the phase three program with with Fox met in PK, you. We do want to make sure that we feel are pipeline and so we are continuing to be very active within business development. We want to continue to stay focused in rare and ultra rare disease, where there is such a high unmet need we believe that we have a strong foundation that is only getting stronger as we focused on late stage development and also our launch capabilities that we think makes this company and attractive partner for for future assets, So stay tuned, but nothing specific beyond that.

Eric Dube: And so we are continuing to be very active in business development. We want to continue to stay focused on rare and ultra-rare diseases where there is such a high unmet need. We believe that we have a strong foundation that is only getting stronger as we, you know, focus on late stage development and also our launch capabilities, which we think make this company an attractive partner for future assets. So stay tuned, but nothing specific beyond that.

Eric Dube: And sorry, one quick, quick one on that is just anything biologics would be considered as well as small molecules and you traditionally small molecule, and then I'll jump back into queue. Thank you so much.

And sorry, one quick one on that it's just anything.

[noise] biologics would be considered as well as small molecules into youve traditionally small molecule and then I'll jump back into queue. Thank you. So much [laughter] yeah. Thanks, Chris So I would say we are we are certainly being open to that and I think we've got the opportunity to really look beyond small molecule I would say nothing's off the table at this point, we want to make sure that we understand what the capabilities that are required for development manufacturing and commercialization or whether it's a small molecule or biologic or you know as we begin to see within you know genetic diseases advanced therapies. So you know I think this is also where the addition of Sandra to our board will help us in making even more informed choices.

Eric Dube: Yeah, thanks Chris. So I would say we are certainly open to that, and I think we've got the opportunity to really look beyond the small molecule. I would say nothing's off the table at this point. We want to make sure that we understand the capabilities that are required for, you know, development, manufacturing, and commercialization, whether it's a small molecule or a biologic or, you know, as we begin to see within, you know, genetic diseases, advanced therapy. So, you know, I think this is also where the addition of Sandra to our board will help us make even more informed choices. Thanks, Chris. Thank you.

Thanks, Brett Thank you.

Our next question comes from the line of Lisa Bayko from JPM Securities. Your line is open.

Eric Dube: Our next question comes from the line of Liisa Bayko from JPM. Your line is open. Hi, yeah, just to parlay off that last question, could you just maybe comment, are you kind of looking for more later stage assets? I know you just recently did a partnership with Alageel Syndrome. Is that more indicative of the kind of early stage investments you're looking to do? Perhaps you could just comment on kind of where you see the need in terms of the state of the pipeline. Yeah.

Hi, Yeah, just apparently off that last question could you just maybe comment are you kind of looking for more.

Ah later stage assets I know you just recently did a partnership for allergy Olson RRAM is that more indicative of the kind of early stage investments you're looking to do.

I, perhaps just comment on kind of where you see the need in terms of the state of the pipeline.

Yeah, Yeah. Thanks, Lisa we'll certainly look at early and late stage I think what we want to make sure that we have an asset that's going to you know fit within our capability and to fit within our portfolio. I'd say you know as we now have moved one asset through phase three we've got two phase threes you know.

Eric Dube: Thanks, Lisa. We'll certainly look at it at the early and in the late stage. I think what we want to make sure is that we have an asset that's going to fit within our capabilities and fit within our portfolio. I'd say, as we have now moved one asset through phase three, we've got two phase threes. We will certainly look to fill that pipeline, but I would say we don't wanna shut off something that is in phase three just because we've got something in phase three, for example. So, a long way of saying we're gonna be opportunistic with regard to the stage of development. We'll assess what the risks are of that asset and make sure that we have a deal structure that is reflective of the risk involved.

We will certainly look to fill that pipeline, but I would say, we don't want to.

Shut off something that is in phase three and just because we've got you know something in phase three for example, so probably a long way of saying, we're going to be opportunistic with regard to the stage of development, we'll assess what the risks are oh that that asset and make sure that we have a deal structure that would be reflective of the risk involved.

Okay, and then just shifting to P. can can you maybe talk like a little bit about.

Eric Dube: Okay, and then just shifting to PCAN, can you maybe talk a little bit about how you're thinking about the data in its totality, you know, short of hitting STATSIG on the primary endpoint, which, of course, would be a no-brainer? What kind of FDA, you know, flexibility do you anticipate also from EMA in terms of this indication and what would be some of the key things you'd be looking for in the data to give you confidence that, you know, there's a clear drug signal?

How you're thinking about.

The data in its totality, you know should've hitting stat, saying on the primary endpoint, which of course would be.

A no brainer you know what kind of SD eight you know flexibility do you anticipate also yeah may terms of the syndication and and what would be some of the key things you'd be looking for in the data to give you confidence that Uh huh.

You know that there's a like clear drug signal.

Eric Dube: Yeah, so thanks Lisa. I mean, obviously, our main focus is to ensure that we have a positive study that meets the terms of the SPA, which would be a three-point difference versus placebo. You know, that said, I'll turn it over to Bill to get his views on, you know, regulatory approaches if for some reason we do not see that.

Yeah. So hopefully I mean, obviously our main focus is to ensure that we have a positive study that that meet the that the terms of the spa, which would be a three point difference versus placebo. You know that said I will turn it over to bill to give his views on you know regulatory approach if for some reason, we do not see that.

Certainly the.

I think at that point, it's going to come down to what.

William E. Rote: Certainly. Certainly.

The signal that you see and how differentiated that is from placebo on durable. The effect is and then a discussion with the agency on both sides of the Atlantic.

William E. Rote: I think at that point, it's going to come down to what... Unknown Speaker 1-1-1, and how differentiated that is from How Durable the Effect, and then a discussion with the agencies on both sides. Relative to how, certainly, both the U.S. Regulatory authorities demonstrated with prior drugs that in situations where there were borderline results from clinical trials, there was regulatory flexibility that was allowed to come to bear, especially in cases where you have such severe disease and No Existence in that space. The agencies are really partnering with you in trying to find... So we're not in the situation where we want to be, but if we are there, think about what's best for patients and how to get that going forward.

Around how significant they view that relative to how we see it certainly both the U.S. and European regulatory agencies have demonstrated with prior.

Drug approvals.

That in situations, where there was borderline results from clinical trials. There was regulatory flexibility that was allowed to come to bear, especially in cases, where you have such severe diseases and no existing therapies I think that.

When you're when you're in that space.

The agencies are really partnering with you and trying to find solutions.

So.

A situation, where we're going to be.

If we are there we're going to certainly.

Be thinking about what's best for patients and how do we have that.

William E. Rote: And we have to, you know, talk to the FDA at that point and develop, Okay, great. And then can you comment on how you're thinking about patient numbers? On one of the KOL calls we hosted recently, there was a report that there were more patients out there than reporting literature. And I was wondering if you could just comment on that.

Going forward.

And we have to talk to the FDA at that point, then develop that path.

Okay, Great and then can you comment on how you're thinking about patient numbers, we I'm one of the Kailong calls we hosted recently a there was a report that.

Like a feeling that there was more patients out there then pardon literature and I was wondering if you could just comment on that.

Yeah, Lisa I'll comment on that this is Eric I would say that you know that there certainly could be and there's there's personally with other rare or ultra rare diseases that one.

Eric Dube: Yeah, Liisa, I'll comment on that. This is Eric.

Eric Dube: I would say that, you know, there certainly could be, and there's precedent with other, you know, rare and ultra-rare diseases, that once there is an effective therapy and then approval, we do see increased numbers. We want to be cautious about that, and so, you know, part of the work that we're doing to prepare for a launch is to update some of the epidemiology within this disease. We know that there hasn't been as much around NBIAs, including PECAN, and so, you know, it's only really recently that there's been literature around this, which led us to the 5,000 worldwide. You know, and once we have completed that work and have anything that would be, you know, updated, we'll certainly share that, you know, but at this point, we're continuing to focus on the worldwide prevalence of 5,000 patients.

You know there is an effective therapy and then approval that you do see increased numbers, we want to be cautious on that and so you know part of the work that we're doing to prepare for launch is to update some of the epidemiology within this disease, we know that there hasn't been as much a round and b I am including Pecan and so you know, it's only really recently, where there's been literature around this which let us to the 5000 worldwide.

And once we have completed that work and have anything that would be you know updated we'll certainly share that.

But at this point, we're continuing to focus on the worldwide prevalence of 5000 patients.

Okay, Great and then just a final question the write down for the Sun's Ah option is that and be fully taken three Q.

Liisa Ann Bayko: Okay, great. And then just a final question, the write-down for the CENSA option, is that it will be fully taken in 3Q?

And that's my final question. Thank you.

Eric Dube: And that's my final question, thank you. Thanks Liisa. Hi Liisa. Yeah, sorry, Eric.

Thanks, Lisa Hi, Lisa.

Yeah, sorry, Eric Yeah, we will take that full write down at once in Q3.

Thank you.

Eric Dube: Yeah, we will take that full write down at once in Q3. Thank you. Our last question comes from the line of...

Uh huh.

Our last question comes from the line of Gino Wong from Barclays. Your line is open.

Unknown Executive: Thank you for taking my questions. I also have a few questions regarding the PECAN program. First, I was wondering what the PECAN ADL natural history data for pediatric patients and adult patients were, more like in terms of the scores and domains affected at the disease onset and then the progression per year.

Thank you for taking my questions I also have a few questions regarding Tecan program.

First just wondering what is the Tecan HDL natural history data for pediatric patients and the adult patients.

More like in terms of <unk> scores and domains affected at the disease that and then a quick question for you.

Thank you we are.

Eric Dube: Thank you, Gina, for your question. I would say that the PECAN natural history has been evolving over the last couple of years with greater recognition of the understanding of this disease. We don't have a published natural history within PECAN, so where we've been focusing our effort is on some of the work that was done to validate the PECAN ADL, which was conducted with about 40 patients and their caregivers to really understand what the symptom burden is across those domains within the PECAN ADL. And, you know, just for background, the PECAN ADL was based on the UPDRF scale in Parkinson's disease given a similar symptomatology of that condition. What we do know about PECAN is that this is a progressive disease.

You enough for your question I would say that the the P. can natural history has been evolving over the last couple of years with a greater recognition of an understanding of this disease.

We don't have a publish natural history within within P. can where weve been focusing our effort is in some of the work that was done to validate the pecan HDL, which was conducted with about 40 patients and their caregivers to really understand what the symptom burden is across those the domains within the P., Kent HDL and you know just for background. The P. Kennedy deal was was based on the U. Pdrs scale in Parkinson's disease, given a similar symptomatology of that condition. What we do know about P. can is that this is a progressive disease.

Eric Dube: You mentioned specifically pediatric patients, and we know that an earlier age of onset does confer a more rapid progression of this disease. And one of the things that we wanted to do in the validation study as well as the fourth study is to enroll a broader population to ensure that we have clinical data and safety data to support the broad use within the PECAN community. And I'll also say that the PECAN ADL was validated in patients age six and older. So we believe that we have, you know, good validity for pediatric patients. And I think we'll be able to assess with a placebo arm here and in the prior study that Noah mentioned to understand what the progression is for. Okay. Okay. That's a long answer, but I think there's quite a bit that we're...

You mentioned, specifically pediatric patients and we know that for an earlier age of onset does confer a more rapid progression of this disease and one of the things that we wanted to do in the validation study as well as the fourth study is to enroll a broader population to ensure that we have clinical data and safety data to support the broad use within within if he can community and also say that the PK deal with validated in patients ages six and older. So we believe that the that we have you know nice validity for for the pediatric patients and I think we'll be able to assess with the placebo arm here and in the prior study that no one mentioned to understand what the progression is for for this condition.

But you know kind of a long answer, but I think there's quite a bit that we're we're really hoping to inform within this disease.

Eric Dube: We're really helping to inform people about this disease.

Eric Dube: Thank you. So, like, another way of asking questions is, like, the baseline scores, you know, between pediatric patients and adult patients, would they be very different, or would you try to balance, you know, like, fit them around similar scores?

Thank you [laughter] like another way of asking question, usually up the baseline scores you know between to be actually pay Shimon adults patients would be very different words, you would try to balance.

I would like to see them around the similar scores.

Eric Dube: Yeah, it's a great question and certainly one that we'll look at once we have the headline data for the overall sample of the FORC study. And that was part of the reason why we included that broad age group within the PCAN ADL validation scale to make sure we understand, you know, where patients are within their disease. And I think, as Noah mentioned, what we're seeing in both the baseline scores as well as the variability in the conduct of the double blind is consistent with our assumptions and how we powered the study. Whether that varies by pediatric or adult will be able to assess. But overall, in the sample, we see that it's consistent with our assumptions.

Yeah, It's a great question and certainly one that will look once we have the headline data for the overall sample of the Fourq study and that was part of the reason why we included that brought age group within the P. can HDL validation scale to make sure we understand where patients or within their disease.

And I think there's no one mentioned what we're seeing in both the baseline scores as well as the variability in the conduct of the double blind.

It's consistent with our assumptions and how we powered the study whether that varies by pediatric or adult we will be able to assess but overall in the sample we are where we see consistent with our assumptions.

Oh, Yeah, Yeah, just just to emphasize or your point that you know thats why I think it was really important for us to get that a third of the patients and the pediatric population. So we can do an analysis. There look independently at that cohort I think also you know there is some evidence to suggest that the pediatric population. The earlier age of onset can progress quicker and maybe related to co at levels that hasn't been proven but it's expected that in those younger groups. There may actually be less Kobe and therefore, they progress more quickly, but you know we are certainly encouraged you know by by the the fact that we're gonna have to see to soon and we're really looking forward, we're excited and speak to our care wells about being able to study. This both in the pediatric and adult population I think they believe that there is potential benefit there and we will see shortly.

Eric Dube: Yeah, just to emphasize, Eric, your point. That's why I think it was really important for us to get that third of the patients in the pediatric population so we could do an analysis there and look independently at that cohort. I think also, you know, there is some evidence to suggest that the Piaget population at the earlier age of onset can progress quicker, and that may be related to CoA levels, although that hasn't been proven. We are certainly encouraged by the fact that we are going to have this data soon, and we are really looking forward to and excited to speak to our KOLs about being able to study this both in a pediatric and adult population. There's potential benefit there, and we'll see shortly.

Noah: Okay, I'm just wondering if you can share, like you mentioned that it is based on your assumption, so what is your assumption for pediatric patients and also for adult patients? And lastly, do you have a pre-specified subgroup analysis for pediatric patients and adults? Yeah, so we're comfortable with where we are now with our assumptions in terms of the pediatric group, and we will be doing a pre-specified analysis in our fiscal analysis.

Okay I'm just wondering if you can share like you mentioned that you know based on your assumption. So what is your assumption for pediatric patients and also for adult patients and the lastly, do you have a pre specify.

Group analysis.

Yeah, sure patient and adult patients.

Yeah. So we're comfortable with where we are now with our assumptions in terms of the pediatric group and we will be doing a pre specified analysis in our fiscal analysis plan.

Noah: Okay, great. Thank you. There are no questions at this time. I would now like to turn back the call.

Okay, great. Thank you.

Thanks Jana.

There are no questions at this time I would now like to turn back the call to Chris Cline.

Unknown Executive: Great. Thank you, Rusty. Thank you all. This concludes our second quarter update. We look forward to speaking with you again here soon. Ladies and gentlemen. Goods to be, Thank you for your participation and have a wonderful day.

Great. Thank you Rusty. Thank you all this concludes our second quarter update we look forward to speaking with you again here soon.

Ladies and gentlemen.

This concludes today's conference. Thank you for your participation and have a wonderful day you may all disconnect.

Yeah.