Good day, ladies and gentlemen, and welcome to the Retrophin First Quarter 2019 Financial Results and Corporate Update Call. At this time, all participants are in a listen-only mode. Later, we will conduct a question-and-answer session and instructions will be given at that time. [Operator Instructions] As a reminder, this call is being recorded.

I would now like to turn the call over to Chris Cline. You may begin..

Great. Thank you, Michelle. Good afternoon, everyone, and welcome to Retrophin's First 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 by our Chief Medical Officer, Dr.

Noah Rosenberg; and our Chief Financial Officer, Laura Clague, for the prepared remarks. Dr. Bill Rote, our Senior Vice President of Research and Development will also be joining us for the Q&A 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 that are expressed or implied by the statement.

Please see the forward-looking statement disclaimer on the company's press release that was issued earlier today, as well as the Risk Factors section in our Forms 10-Q, 10-K filed with the SEC. In addition, any forward-looking statements represent our views only as of the date such statements are made, May 7, 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 to Eric.

Eric?.

Thank you, Chris, and good afternoon, everyone. We continue to advance our pipeline to address significant unmet need for people living with rare diseases. Our execution in the first quarter has positioned us to reach the next key milestones this year for each of our late-stage programs.

Our lead program evaluating fosmetpantotenate for the treatment of PKAN remains on track for a top-line readout from the pivotal FORT Study in the third quarter of this year. We are eagerly awaiting the results, which if positive have the potential to bring the first approved treatment to patients living with this rare neurodegenerative disease.

We've seen a great dedication from patients and families in the FORT Study and we are thankful for their continued participation and commitment. We further strengthened our fosmetpantotenate team with the addition of global medical and commercial product leaders.

And they are guiding our efforts during this exciting time as we progress our preparation work for both U.S. and European filings, as well as commercial launch. We also continue to make progress with our two Phase 3 programs with the potential to make sparsentan the new treatment standard for rare kidney disorders, FSGS and IgA nephropathy.

Together, these two diseases represent an opportunity for us to potentially have a positive impact on the treatment paradigm for as many as 150,000 patients in the U.S. and similar numbers in Europe. Noah will talk a bit more about this in a minute.

But we are pleased with the building enthusiasm for the sparsentan program within the nephrology community. In FSGS, our Phase 3 DUPLEX Study remains on track to deliver our second pivotal readout, which we expect to come during the second half of 2020.

The PROTECT Study to evaluate sparsentan for IgA nephropathy continues to build momentum after starting at the end of last year. Investigator engagement is high and site activation is going to plan. Overall, we remain optimistic about sparsentan's potential to be a first-in-class therapy for FSGS and IgA nephropathy.

And we will further our efforts to build upon the strong foundation throughout the year. We are also nearing a potential inflection point with the CNSA-001 collaboration. We have been pleased with the progress the team at Censa is making.

Since our last call, they completed randomization in the Phase 2 proof-of-concept study evaluating CNSA-001 in patients with PKU. And we are looking forward to evaluating the outcome. We understand from Censa that the program remains on track to deliver top-line data in the next couple of months.

And thus, the decision on our option is expected to come in the third quarter of this year. In order to make our decision on the option, we will be conducting an assessment of the full dataset.

We will also be assessing regulatory input, including participating in the planned FDA interactions, as well as hosting an advisory board to leverage the input from leading experts in the field to refine our outlook of the competitive landscape.

I know many of you have been asking about when to expect the results of the Phase 2 Study to be made public. We recently worked with Censa to align on the disclosure plan in the event we exercise our option to acquire. That would allow us to make the Phase 2 data available to all of you at the time of our decision during the third quarter.

This takes into account the needs of our collaboration and will allow us to give the full context of our decision in the event we exercise. Lastly on this program, we are planning for success. Our teams are working to ensure we have the appropriate resources to quickly move CNSA-001 forward, if we trigger our option.

Outside of the pipeline and partner programs, the base business continues to benefit from new patient starts and the first quarter marked another consecutive period of year-over-year organic growth. Thiola performance continues to be steady. And our team in the field continues to make a positive impact with patients diagnosed with cystinuria.

The bile acid portfolio came in slightly below the same period last year, which is attributable to the uneven nature in which patients with these ultra rare indications initiate and receive treatment. As is normally expected in our business, we experience higher gross to net discounts in the first quarter, driven by insurance resets in the New Year.

This shift was in line with our expectations and we anticipate moving back into normal levels over the coming quarter as we have seen in years past. Notably, we started the second quarter with a strong month of April and we remain on track to meet our full year growth projection for 2019.

We are also preparing for the upcoming PDUFA date for the new formulation of Thiola on June 30. We are fortunate to have a very experienced team that has been working with cystinuria community for the last 4 years.

They are well positioned to educate and raise the awareness of the opportunity to potentially improve the Thiola experience and ensure seamless access when we look to the launch in the third quarter. Let me now turn the call over to Noah for a clinical update.

Noah?.

Thank you, Eric, and good afternoon. I'm proud of our team's efforts, which have led the advancement of all three of our pivotal program and a strong start to the year. Our lead program fosmetpantotenate for the treatment of PKAN continues to make solid progress as our Phase 3 FORT Study advances.

As many of you will recall, complete enrollment of FORT in December. So at this point, majority of patients have completed a pre-specified 24-week double-blind period of the trial. We remain pleased with the study conduct and with patients progressing into and remaining in the open-label portion of the study.

Most importantly, as Eric mentioned, there are on track deliver a top-line readout in the 24-week safety and efficacy data in the third quarter. Our biometrics team and CRO continue to do the necessary validation work to ensure, we'll have a high quality readout.

And we look forward to sharing results with all of you and the PKAN community add that time. In parallel, our development team continues to prepare our regulatory package to ensure that be a position to submit our NDA and MAA applications in 2020. Given the current lack of treatment options and the significant unmet need for patients living with PKAN.

We want to be in a position to make fosmetpantotenate broadly available as quickly as possible. I will now shift over to sparsentan, we're pleased with how the enthusiasm and the awareness of our program continues to rise within the nephrology community.

We recently had the opportunity to engage with key opinion leaders at the World Congress of Nephrology meeting in Melbourne, Australia. We were able to continue raising awareness of our ongoing Phase 3 trial as well as positive results from DUET Study and open-label extension.

As many of you may recall, the data from the DUET open-label extension showed the ongoing sparsentan treatment in patients with FSGS over 84 weeks resulted in sustained and progressive antiproteinuric effect and an increasing proportion of patients, who achieved FSGS partial remission of proteinuria.

It also showed the newly initiated immunosuppressive therapy had no meaningful impact on the efficacy and safety measures of sparsentan treatment during the period.

Along with other datasets presented at the meeting that support the potential nephroprotective benefit of dual inhibition with endothelin antagonism and RAAS blockade, there was a positive sentiment in our teams in one-on-one discussions with thought leaders at the meeting.

With appear to be growing enthusiasm for sparsentan utility and FSGS and IgA nephropathy. The pivotal Phase 3 DUPLEX Study evaluating sparsentan and FSGS continues to advance and remains on track to have a top-line readout for the interplanetary assessment in the second half of 2020.

We still have a number of sites coming online through the balance of the year and we're looking forward to getting them off and running. We've been able to leverage the DUPLEX footprint to move quickly with pivotal PROTECT Study for IgA nephropathy and the initial trends are encouraging.

Through the balance of the year, we'll remain focused on execution of the near-term milestones to advance each of our three pivotal programs. I look forward to sharing more with you, as we approach key inflection points like the top-line readout from the FORT Study in the third quarter. Let me now turn the call over to Laura for financial update.

Laura?.

Thanks, Noah. During the first quarter, net product sales from our commercial portfolio grew to $39.6 million, a 3% increase over the same period in 2018. We reported a GAAP net loss of $41 million for the first quarter of 2019. After adjusting for non-cash expenses and income tax, we reported a non-GAAP net loss of $26 million.

On a GAAP basis, R&D expenses for the quarter were $33.4 million for the first 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 for our fosmetpantotenate and sparsentan, including our three Phase 3 trial.

On an adjusted basis, R&D expenses were $31.5 million for the first quarter. Relevant non-cash expenses for the first quarter included $2 million of stock-based compensation and amortization.

Selling, general and administrative expenses for the quarter were $32.7 million, the increase over the same period in 2018 is largely attributable to headcount and support of our operational growth and increased legal fees.

On an adjusted basis, non-GAAP SG&A expenses for the first quarter were $23.2 million, significant non-cash adjustments for the quarter consistent of $9.5 million in stock-based compensation and depreciation and amortization.

In the first quarter, we made a portfolio decision to discontinued further development of the L-UDCA program, which resulted in a net non-cash P&L charge of $7.5 million during the period. The company acquired the rights to L-UDCA in 2016 for $0.5 million.

As we advance our three pivotal program, we continue to leverage our strong financial foundation with $447.6 million in cash and cash equivalents as of March 31, 2019. For the balance of the year, we continue to expect R&D expenses to increase modestly from current levels.

As we've said previously, there may be an uneven nature in R&D expenses as we manufacture clinical material and scale up for commercial readiness, but we do anticipate continuing modestly higher as our studies advanced in the clinic. SG&A for the remainder of the year should be relatively stable with the potential for minor increases at times.

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

Eric?.

Thank you, Laura. On our year-end call a couple of months ago, I talked about my evaluation of the organization as a new leader. I'm pleased to report that Retrophin is in a strong position to deliver fosmetpantotenate and sparsentan in the coming years, and I'm confident in the capabilities of our team across the organization.

It became clear that in order to maintain the patient focus on our key pipeline assets and further the pursuit of our mission in the years ahead, there were few adjustments to be made. As Laura mentioned, we discontinued our L-UDCA program during the quarter with the belief that it will sharpen the focus on advancing our late-stage pipeline.

We also made the decision to transition to a more focused commercial role on the executive team. This shift will allow our team to maximize the success of our upcoming product launches and to reach as many patients as possible with our new and currently approved therapies in the years ahead.

As a result, our Chief Operating Officer, Neil McFarlane, will be departing at the end of this month. Neil's leadership, commitment to patients and continued support of our mission has helped the company evolve and reposition us as a leader in the rare disease community. And we are all grateful for this work and dedication over the last several years.

We are entering a period of significant growth and we will remain focused on delivering on our near-term milestones to create value this year. It is clear that fosmetpantotenate and sparsentan are the center of our growth for our organization. And we are looking forward to the pivotal readout next quarter.

Each of these three programs offers an opportunity for us to reach significantly greater number of patients and transform our ability to serve the rare disease community.

With the upcoming option decision on the Censa collaboration and anticipated launch of the new formulation of Thiola in the third quarter, we also have opportunities this year to make strides towards improving the current treatment options for patients with PKU and cystinuria.

We are well prepared to recognize value from all of our programs as we reach these key milestones later this year. And we look forward to updating you on our current continued progress. Let me turn the call back over to Chris, to open it up for questions.

Chris?.

Thanks, Eric. Michelle, can we go ahead and open the lines for Q&A, please..

[Operator Instructions] Our first question comes from Geoff Meacham of Barclays. Your line is open..

Hi, this is Greg Harrison on for Geoff. Thanks for taking our question.

With regards to the CNSA-001 asset, could you give us any additional color on how you're going to assess the decision whether to acquire the asset when you see the data? And is there a fee reduction level we should be thinking of as the minimum bar or is there some other criteria that you see as important in making this decision?.

Yeah, thank you, Greg. So I'll share with you my thoughts and then I'll ask Bill Rote to add anything else. So essentially, we're primarily going to be looking at the clinical profile of the CNSA-001 asset. We do believe that there is still unmet need in this established market.

And we want to make sure that we would be able to deliver a product that meets the unmet need in a way that the current assets on the market do not. So we're going to be looking certainly at the clinical profile.

But we also want to look at what the regulatory requirements are; what's the pathway and speed by which we'll be able to bring this asset to market, particularly because it is a competitive market. But we also are going to be looking at how we think that this PKU market will evolve over time, given that it is dynamic.

There would likely be new entrants that are currently in the non-clinical or pre-clinical phase. So we want to make sure that we understand what the addressable market will be. Those are the three key areas that we will be looking at over the next couple of months before we make a decision.

And now, I'll invite Bill to talk a little bit about what we'll be looking at for fee reduction and the efficacy data..

Certainly, I mean, as you said, it's a holistic view of the whole program. Specifically, with fee reduction, I don't know that we've established a specific numerical cut off for which we need to hit. But I think it's more a qualitative view of clear superiority over the existing standard of care.

So for those patients who are responders, you see a significantly improved response. And for those who are weak or non-responders, can you push them into a point where they become responders? Those would be the two categories, where we'd really want to see a difference..

Great. Thank you.

And, if I could just follow up, have you thought about - I don't know if it's maybe early, but about pricing, if you decide to acquire the asset and kind of how you'd fit in the market with Kuvan and PALYNZIQ in there, and just how you see the overall competitive dynamic evolving?.

Yeah, I mean, certainly, we will - we're continuing to look at what those trends look like as well as potential new entrants, including the potential for generic Kuvan. And certainly, all of those would play into our thoughts on pricing. And again, we want to make sure that most importantly, that this asset would be delivering on an unmet need.

And we think that is the primary input into our pricing decision. But we've not disclosed what our thoughts are specifically on pricing. Thanks, Greg..

Great. Thanks so much..

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

Thanks for the question.

For the upcoming FORT Study, do you have a sense of how many patients have rolled into the open-label follow-up portion of that study? And could you maybe speak to the base line population enrolled, how heterogeneous it was or the age ranges and concomitant medications?.

Yeah. Hey, Tim. Certainly, we've been pleased with the progress so far. And I'll invite Noah to share a bit more detail on both of your question..

Hey, Tim. So as far as the open-label portion of the study, the first part of your question, we're giving specific numbers. But we can say the majority of patients have now completed the double blind portion and have entered the open-label. We just emphasize we remain encouraged by the retention we've seen in the open-label as well.

And we, in terms of the demographics, reminder, we remain blinded to the study. We only really see a limited amount of information. But I would say, overall, we're pleased with the study conduct. It's led to a representative population. We mentioned previously that about two-thirds are adults and one-third pediatric.

I think it's fair to say that it's consistent now as well. And we just want to thank the patients and families, of course, for participating and making this possible. And then, finally, in terms of the - some of the other demographics, the median PKAN rating for instance, the data isn't considered final until database is locked.

And we can't share specifics, but I can tell you that the baseline PKAN-ADL results are similar to what we saw in the published PKAN-ADL validation study, which was in the upper 20s. So that's reflective of our initial assumptions and design.

We feel like we've enrolled the right patients to be able to show an effective fosmet does what we expect it to do. And hopefully I answered your question there, Tim..

Yeah, definitely.

And maybe can you remind us what the differences are between the PKAN specific pool and the UPDRS Part II and III?.

Yeah, so essentially the UPDRS Part II, which is the activities of daily living part of the Unified Parkinson's Disease Rating Scale. There were - the validation study that Noah mentioned really was done with 41 patients or their caregivers.

And a lot of the work that we did with that community was to understand what are the specific symptoms that are hallmarked to PKAN versus those that are in Parkinson's disease. So that's the approach that was taken and the intent. And Noah can speak to those couple of items that were changed from one to the other..

Yeah, so, Tim, in terms of PKAN-ADL, which was adapted from the UPDRS Part II. There were two items that were removed, which are tremor and freezing. They weren't felt relevant to the population. There was item that was added, which is problem sitting independently or getting out of a chair.

And I think I just want to also mention that overall, when look at these scales, the [UKPDS] [ph], the way the scale is designed, if you remember, there are 12 separate domains. There were - essentially they're four point scale each. And a 1 point change on any one of these domains was designed such that that will be a clinical relevant effect.

So I think it's important to keep that in mind. Again, we saw as you recall using the - UKPDS II in the compassionate use patients, double-digit changes. But even modest changes with the PKAN-ADL would signal a clinically significant meaningful effect..

Great. Thank you for all the details. And maybe if I could just sneak one more in, I apologize.

But you did mention that you are hearing more KOL support, especially [WCN] [ph] Could you just may be talk holistically what's leading to that interest and that support? Is it kind of comfort around the [mechanism of action] [ph], is it comfort around fluid retention, which may be - if that was an issue with the class prior? Or what's around that KOL interest and support?.

I think, there are a few things that are feeding into that. I think number one is, in fact that we've got the DUET long-term data, and we're - we continue to demonstrate that the product to see well tolerated as opposed to some of the other folks that are coming in that a little earlier on are less proven.

So I think that there is a lot more emphasis there on that durability and that long-term safety. I also think, specifically at that meeting if you recall, there were two large outcome studies that were presented SONAR and [CRIDNS] [ph].

I think both studies taken together in the diabetic nephropathy population is slightly different than what we're looking at. But in this nephrotic syndrome or nephropathy population demonstrated that there is residual risk, and there's potential for these drugs to actually improve or reduce that residual risk and prove outcomes.

And these were hard outcome studies. Things like double serum creatinine end-stage renal disease.

So - and then finally, I'll just add the SONAR data, while it was different compound, it was also utilized in ERA, on the background of ACEs and ARBs or RAAS inhibition, which I think adds even more credibility and credence to the concept of combining both of those mechanisms and provide support for that rationale in terms of the potential for nephroprotection, as well as you potentially down the road improving overall long-term outcomes..

It's great to hear. Thanks for all the detail..

Our next question comes from Maury Raycroft of Jefferies. Your line is open..

Hi, everyone, good afternoon and congrats on the progress. First question is on sparsentan for the Phase 3 DUPLEX study. Assuming that you succeed on FPRE, and power for accelerated approval there.

What's the best way to try to understand how eGFR slope differences could play out at 108 weeks? Can you comment on your expectations for eGFR?.

Hey, Maury. Yes. So Noah, you want to take this one..

Well, this is Bill. I think that expectations in the FSGS population is that, absent treatment or even best standard of care, those patients are going to lose three to five mils of eGFR each year. We're expecting to see a delta at the end of that, that statistically significant and we powered off of that.

We haven't revealed what that powering is or what the specific effect size is. But that can give you some of the generalities around it.

Is that helpful?.

That's helpful.

And I guess also about the relationship between proteinuria and eGFR at 36-week, so we get some insight or greater confident into how eGFR would play out at that point, I guess?.

So at that point, it's not clear if there is enough time at 36 weeks to show the difference. So one of the reason why we're running the longer study out to two years and that's why it's build in such a way that you have the primary review at 36 weeks looking at proteinuria and then the confirmatory endpoint at two years for eGFR.

The combination of effect size and variability leads you to the point that you need a longer study for those two lines in diverse..

Thanks, Bill. I think the other thing that I would add is that the endpoint is used for proteinuria, which is the FSGS partial remission endpoint, which is really a composite of 40% or greater reduction in baseline proteinuria as well as a proteinuria level at 36 weeks of 1.5 or below.

It's really based on modeling that was done to look at survival curves of renal health, whereby those that show complete or partial remission on that endpoint actually have better long-term renal outcomes. And so I think that was a large basis for looking at that endpoint, which we believe based on DUET, you can show a 36 weeks.

But then would be or could be predictive of longer-term renal function..

Got it. Very helpful.

And then just quickly on Thiola, I'm wondering, if you can provide any more color as to what went in to the filing package for the NDA? And then maybe - the second question to that, as the company strategic shift to focus more on your current pipeline in the commercial opportunities, any thoughts on label extensions with the Thiola?.

Yeah. Thank you. So we've not disclosed much about the new formulation of Thiola, we want to make sure that - we certainly will share that at the time of the approval, which is next month.

And so we'll certainly share more, but I can tell you that the package on the formulation was very much tight to what we heard from the patients that we serve and some of the challenges with the current formulation. So again, we're on the eve of the PDUFA date at the end of next month and we'll certainly share more then.

In terms of further label expansion, for that and for any of our products that's something that we continue to look out in lifecycle management, how do we continue to develop more evidence, et cetera. But it's not something that we have decided to disclose at this point..

Okay. Thank you very much. Thanks for taking the question..

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

Hi, thank you for taking my question. I was just hoping you could elaborate a bit on, I guess, the World Congress of Nephrology comments. There were data presented from atrasentan, which is a more selective endothelin A receptor antagonist.

Could you just talk about any read-through you see to sparsentan and maybe touch on why FSGS and IgA nephropathy are more ideal indications versus diabetic nephropathy for this mechanism?.

Yeah, Michelle, it's Noah here. So I think with atrasentanm, there are - in this population of diabetic nephropathy, it's a little sicker population then what we're seeing and there tends to be higher rates of heart failure and other complications. So in addition, the A properties may confer some of those worse outcomes.

But it was actually heartening to see that even in that context the heart failure was managed actually with diuretics even with that compound, in that population. With our compound in FSGS was significantly lower and more favorable properties that gives us a lot of confidence in terms of the treatment in these patients.

We actually look at the DUET data carefully for any signals and we've seen some fluid retention as you know, was managed with diuretics, but no cases of heart failures. So I think from a safety standpoint overall that data gives us a very good solid basis for us to proceed.

In addition to the - all the solid foundation from DUET that we have in terms of the overall efficacy data that was alluded to before..

Okay. Thank you..

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

Hey, good afternoon. Thanks for taking the question. Just one on - or a couple on fosmet. I was wondering, if you could just remind us really regarding the dose that you'll be exploring in the Phase 3 versus that is on - in the open-label for the individual case reports on this drug? Number one.

And then maybe number two, if you could further elaborate on components of the UPDRS that changed in the single patient studies, if there are included primarily in the PKAN-ADL or how should we think that mapping one to the other and have you actually mapped those results onto PKAN-ADL. And then one follow-up. Thank you..

All right. So Bill, would you like to take those questions..

Sure. The Phase 3 Study currently is 300 milligrams three times a day. I think your question was how does that compared with those individuals in the compassionate use setting they range from 120 milligrams three times a day, up to 300 milligrams per day. So we're in that ballpark.

In Phase 1 Study, we went as high as 3,600 milligrams in single administration, and had pretty reasonable tolerability even at those higher doses. The other aspect of your question was the comparing and trying to draw bridge from the compassionate use individuals and the effect we saw, measured in the UPDRS scale and mapping that over to PKAN-ADL.

The only components that were removed were freezing and tremors, which really don't occur in patients with PKAN. So it should be a net neutral change, when you go to PKAN-ADL, you've had one more components that's not assessed in those patients, which is the ability to sit independently and can you get out of a chair unassisted.

So that domain was new and would be the only difference. So they matchup much more than the diverge. The difference in some of the UPDRS scales, there is one that's patient reported and one that's physicians reported, where PKAN-ADL is either patient or caregiver reported depends on the settings. So I hope that helps you with your question..

Absolutely. Thanks.

And then just with regards to on, I suppose, the treatment effect that you expect to see that's clinically meaningful on the PKAN-ADL, what should we be thinking about? And then thinking about pediatrics versus adults, any expectation that you might be scale a bit more one group versus the other? And if one were to be, I suppose, more clinically relevant and the other not, would you file an NDA in just one population? Thank you..

Yeah. I'll just address. So the first question is around the powering and just emphasize again how the PKAN-ADL scale works is 0 to 48 points again whole domain 0 to 4 rating. And so while we would anticipate that a low-single-digit improvement on the PKAN scale or placebo would be meaningful.

Again, we did see these double-digit changes as Bill alluded to.

So I think the answer to the question is we do see modest changes, we would expect those to be clinically significant with regard to subpopulations, as you now, it's a fairly small group here, a patients, but it is rare disease and these studies aren't really power to show P values in subpopulations.

So I think, it's important to look at every data point and really understand the totality of data and how we're improving disease in these patients.

And even small again modest changes in the pediatric population in a disease where there is no approved treatment would be meaningful and would be something that would be looked upon and we believe quite favorably..

Our next question comes from Liisa Bayko of JMP Securities. Your line is open..

Hi, thanks for taking my question. I just want to ask a little bit more about the FORT Study and how much you thought about or know about the natural history, when looking at the endpoint, sort of over that 24-week period. Would you expect kind of as a background change? Thanks..

Yeah. I'll just say that it's hard to gauge that or answer that question. It's a rare disease that hasn't been well studied. We don't know a ton about this population. What we have heard is that there is typically steady worsening of patients with - occasionally you can see what's referred to episodic. I'm not sure that's the best term.

But maybe stepwise worsening, so a background of modest reduction with stepwise, flares are worsening of disease. We talked to our experts and the folks that helped us power this study. And while we don't think that at 24 months we're going to see maximal effect - sorry, 24 weeks, we're going to see maximal effect.

We do think that we are in a position to be able to see a clinically meaningful effect at 24 weeks, based on their knowledge of the disease state..

Okay. Great. And then, could you remind us how frequently you're going to be kind of going through the questionnaire, because I know it's over time, correct? The way you're measuring, it is over time. It's not baseline versus week 24..

Yeah, we have measurements frequently throughout the study at various time-points. And I think that that's important to note in the way the measurement, the robustness of the data. So it's not just change from baseline.

And we consider all the data-points, including week 3, week 6, week 12, week 18 and week 24, which are the measurements, the time-points in the study..

All right, thanks a lot..

Thanks, Liisa..

Our next question comes from Joseph Schwartz of SVB Leerink. Your line is open..

Great. Thanks very much. So continuing on that fosmet theme, I was wondering if you can provide any information on the powering assumptions that went into the trial.

What degree of separation needs to be seen based on the variability that you expect in order for the trial to be, quote unquote, successful?.

Yeah, thanks, Joe.

Bill, do you want to take this?.

Sure. We haven't revealed what the specific powering is, but - and I think Noah mentioned it previously, was low-single-digits is what we need to see as far as the separation between the two groups..

Okay. Can you tell us what percentage of patients who are eligible have opted to participate in the open label extension study for the forward study? Even it sounds like you could be tracking these patients longer term and maybe they'll need greater separation over time..

I think that's a really good point, Joe. Yeah, all patients have opted to cross-over from the double-blind into the open-label extension. And we will continue to collect that data out long-term and have a good amount of information to assess that long-term function..

Great. Okay, thanks. And then, on Thiola, next gen Thiola, can you - I understand you don't want to reveal the attributes of the product, but as - quite yet.

But can you talk about the robustness of the data that you generated to support the NDA and how well do you think that will satisfy the FDA's demand for the review?.

Yeah, so we're currently in the process with that filing. And we've not disclosed the specific engagements that we had. But we believe that we're on track for that. And, obviously, because we're still on that discussion with FDA, we don't yet have final labeling. We just want to be cautious.

But we believe that what we've submitted will support the approval next month..

Okay, great. And then, one last one for me, if I could, you currently don't have much of a rest of world presence, so I was wondering how you might envision this could change any or all of your pipeline bears fruit..

Yeah, thanks, Joe. So, certainly, that is something that we are actively looking at. We are in the process of building a European organization. We've got a head of Europe and part of our expansion has been building out that team over the last couple of quarters, particularly in preparation for the fosmetpantotenate launch.

We have actively engaged in looking outside of Europe and U.S., particularly with sparsentan, where we know that the rates of FSGS and IgA nephropathy are high, and there is unmet need. And we're looking at different models for what would be best for us in delivering that value.

But we've not disclosed specifically what that model is outside of the U.S. and Europe..

Sounds good. Thanks again..

There are no further questions. I'd like to turn the call back over to Chris Cline for any closing remarks..

Great. Thank you, Michelle. Thank you everybody for joining. This concludes our call for the first quarter and we look forward to updating you in the near future on our progress..

Ladies and gentlemen, thank you for your participating in today's conference. This does conclude the program. And you may all disconnect. Everyone, have a great day..