Q3 2022 Travere Therapeutics Inc Earnings Call
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Good day and welcome to the traverse Therapeutics third quarter 2022 by natural results and corporate update conference call.
Today's conference call is being recorded at this time I would like to turn the conference call over to the Vice President of Investor Relations. Naomi Eichenbaum. Please go ahead Naomi.
Thank you Carrie and good afternoon, and welcome to your ear Therapeutics third quarter 2022 financial results and corporate update call. Thank you all for joining us.
Today's call will be led by our Chief Executive Officer After Eric E Bay, Eric will be joined in the prepared remarks, My Doctor July and Wright, our Chief Medical Officer.
For now our Chief commercial officer, and Chris Klein, Our Chief Financial Officer.
Dr. Bill Rote senior Vice President of research and development will join us for the Q&A session. Before we begin I would like to remind everyone that statements made during this call regarding Barbara that are not historical facts are forward looking statements within the safe Harbor provision of the private Securities Litigation Reform Act of 99.
Forward looking statements are not guarantees of performance.
Both known and unknown risks uncertainties and assumptions that may cause actual results performance achievements to differ materially from those expressed or implied by the statements.
See the forward looking statement disclaimer on the company's press release issued earlier today as well as the risk factors section in our Form 10-Q, and 10-K filed with the FCC and.
In addition, any forward looking statements represent our views only as of the date such statements are made October 27, 2022 and for the year, specifically disclaims any obligation to update such statements to reflect future information events or circumstances with that let me now turn the call over.
Eric Eric.
Thank you Jeremy and welcome to persevere.
And good afternoon, everyone.
During the third quarter, we continued to execute towards our vision of being a leader in the global rare disease community.
We did this through the continued development of our pipeline with the objective of positioning it for sustainable diversified growth for years to come and by strengthening our organization to support broad access to our approved medicines, while being in a position to meet the need of patients as our potential new therapies become available.
Notably during the quarter, we continued our efforts to position <unk> to become the first non immunosuppressive therapy for Iga nephropathy, and <unk> as a potential new treatment standard if approved.
A couple of weeks ago, we provided a regulatory update on our NDA for <unk> in Iga nephropathy that is currently under priority review with the FDA for Subpart H accelerated approval.
In that update we were pleased to report that we had received a draft label on time.
And that no advisory committee as expected.
No new data or trials had been requested as part of the review process.
Our late cycle meeting interaction the FDA did unexpectedly asked us to great liver monitoring into our plant reps.
I am pleased to report that we have submitted our proposed updated reps and we recently received confirmation of the expected three month extension of our could do the target action date, which is now February 17th 2023.
Perhaps most notably we have been very pleased with the continued enthusiasm for the strength of our clinical data supporting the profile of <unk>.
We have continue to hear this from the nephrology community since the update was provided a couple of weeks ago.
I'd also like to highlight that while the submission of a revised Rems has resulted in an extension of our <unk> target action date, our teams were well prepared and in a strong position to launch this November .
This is a great Testament to Peter and his team and to the whole organization as it is no small feat to prepare for the launch of a potential new treatment standard.
We will utilize the added time to further enhance our understanding for how we can best support patients and providers in the Iga nephropathy community and be even more prepared for a successful launch.
Outside of the U S. We were very pleased to have the EMA, except who'll review the conditional marketing authorization application for sports center for the treatment of Iga nephropathy.
We look forward to working closely with our partner CSL before throughout the review process and.
And we expect a review decision on a potential approval in the second half of 2023.
Lastly on sports Medicine, we continue to be pleased with the progress of our ongoing pivotal duplex study in <unk> and.
And we look forward to top line data from the two year end points in the first half of next year.
If the data are supportive of an S. S. G S regulatory submission and assuming approvals and Iga nephropathy, we would anticipate being in a position to submit an NDA in the second half of next year and the subsequent variation to our European CMA application.
Elsewhere in the pipeline are pegged at about <unk> program for classical home assistant urea or <unk> continues to advance Julien.
Julia will be going into a bit more detail shortly but we're pleased with our regulatory interactions during the quarter, which enables enabled us to advance on the path towards utilizing a total home assisting biomarker.
Primary endpoint in a phase III study.
Let me now I'll turn the call over to Julia for the clinical update July .
Thank you Eric and good afternoon, everyone.
We continue to hear regularly that physicians and patients are seeking non immunosuppressive treatment option to treat the rare kidney disorders and.
Importantly, <unk> is the only molecule in development, which blocks to causal pathways in the pathophysiology of kidney disease progression, namely the endothelin and angiotensin pathway.
The relevance of this dual inhibition in a single molecule is that for a second have shown the greatest reduction in proteinuria.
To date for a non immunosuppressive agent and a pivotal study against an active control in Iga nephropathy.
If approved <unk> would be the first and only non immunosuppressive treatment approved for Iga nephropathy, and we continue to have confidence that it can ultimately become a new treatment standard.
As it relates to our NDA under priority review for <unk> and Iga nephropathy.
We noted in our update in our update two weeks ago that we were pleased to have received a draft label and that the overall process appears to be moving well.
As Eric highlighted we did receive an unexpected request for a rems to include liver monitoring.
I will reiterate the FDA communicated to us that this request is being made in part because serious drug induced liver injury has been associated with other treatment options that intervene in the endothelin pathway and that the <unk> database will not be final while being reviewed under the accelerated approval pathway.
Additionally, it was highlighted to us that there was a desire to have agitation and monitoring is this would be the first time nephrologist would be using a medicine, which blocks endothelin.
Most importantly, there have been no reported clinical diagnoses as first langton related liver injury in the program to date.
And our adverse events of interest related to ALC ASD elevation in both of our phase III studies spanning nearly 800 participants at the time of the data analyses were comparable between Super Clinton and active control Irbesartan.
As you heard from Eric we have submitted our updated runs proposal back to the FDA.
Our goal is to make the rems effective for liver monitoring and convenient for patients and their physicians and support staff and.
And there've been a number of examples that we've been able to learn from the recent weeks.
It's also important to note that many nephrologist and their practices are already familiar with the rems process.
Additionally, nephrologist routinely order and monitor labs for every patient monitoring liver function test should be seamless with their current clinical practice.
We recently received confirmation of the three month extension and our new <unk> target action date of February 17th of next year.
We look forward to continuing to work with the FDA through the labeling and review process.
We will use the opportunity provided by the extension to further our Iga nephropathy disease State education for physicians and our work with the support of patient advocacy groups in the nephrology field.
Our <unk> program for <unk> continues to progress as planned.
We believe that we are in a path to an F&D a submission next year, if the perfect and it's approved for Iga nephropathy and the two year data in our pivotal phase III duplex study progresses in a favorable manner.
To that end, we are pleased with the continued conduct of both the ongoing duplex and protect studies and we remain on track for the top line Readouts from the two year end points next year.
For FX, Yes, we expect this will be in the first half of 2023 and for Iga nephropathy in the second half of 2023.
Lastly on <unk> ASN kidney week, it's occurring next week. This is an excellent opportunity for us to engage with the nephrology community.
We look forward to sharing insights from our growing body of research first of all our content in both Iga nephropathy and FX, yes.
Including our two oral presentations and nine poster presentation.
I'll now turn to our <unk> program, which continues to advance towards phase III development I.
I am pleased to report that we believe we have line of sight to completing enrollment in the sixth cohort of our ongoing phase <unk> study and that we continue to gather data from patients from the first five cohorts in the open label extension.
All of which will be critical informing our views for a pivotal study.
We also completed our second official biomarker interaction with the FDA and believe we're making sound progress towards utilizing total home assisting as a primary endpoint in a pivotal study.
We will be utilizing our learnings from this interaction to guide our upcoming multi disciplinary meeting afforded by breakthrough therapy designation to further align on the design of a pivotal study.
In parallel to the clinical and regulatory work, we continue to work through the burden global supply system to make progress on building supply for the pivotal phase of development and commercial readiness.
Overall I am very pleased with the continued progress of our pipeline and the potential for us to continue to deliver new greatly needed treatment option to the rare disease community.
I'll now turn the call over to Peter for the commercial update Peter.
Thank you Julie.
During the third quarter, our commercial organization continued to deliver our brew brothers and built through the momentum towards the potential launch of <unk> syndrome, and Iga nephropathy.
So what are you approved.
We had another quarter of solid demand across our commercial portfolio.
We are pleased with the continued performance despite evolving competitive landscape.
As we have talked about throughout the year, we are seeing the impact of generic dynamics affecting net sales.
Nick this to materialize further in the quarters ahead.
Overall, we remain pleased with how we have continuously identified greta and supported patients and assistant urea community.
Our bile acid portfolio continued to deliver solid growth in the third quarter.
The global fuel team has had a long standing dedication to educating pediatric geneticist as well as Herpetologist and these efforts have been key to go bumps continued success.
Our established commercial footprint allows us to build upon our strengths as we prepare for a successful launch of <unk> in Iga nephropathy if approved.
Over the last eight years, our commercial organization has built a track record strong execution and identifying freezing and survey people affected by rare diseases.
This has allowed patient access to treatment and support for both indications.
We completed our recruitment efforts to expand our team in preparation for the sporting good logged in Iga nephropathy.
And as Bill the season's Nephrology field force.
This established sales group has an average of nearly 20 years specialty experience mostly within nephrology.
The team has completed initial training and is gaining familiarity with the community you said expect two centers.
Of note our team was prepared for a launch of <unk> in the liver if it would have been approved and as a result, we have great confidence that we will be even better position in February .
After speaking to patients in the fall just about new rems requirements of liver monitoring we believe that the potential for sports intend to become a new treatment standards and Iga nephropathy remains unchanged.
As you heard from July the need for non immunosuppressive treatment options to address the extra spatula for people living with Progressive Iga nephropathy has never been greater.
It's a dual endothelin.
Receptor antagonist.
Our simple only treatment in development.
Pivots to critical pathways to the pathophysiology of the disease.
We believe that is what has contributed to sports to sports interim demonstrating the ability to reduce proteinuria by nearly 50% in a pivotal phase III study against.
Control.
With our results in the pharmaceutical would be the first non immune suppressive treatments indicated for Iga nephropathy is approved.
We continue to believe.
There will be an addressable patient population of 30 to 50000 patients at launch in the United States.
Based on what we know today, the initial Onboarding and education in the Rems process and the frequency of monitoring could result in a more gradual uptake than we had originally expected.
We will continue doing additional research to further understand these dynamics.
We have already learned quite a bit from studying some of the other programs that has done very well with similar type title friends.
We believe the key to our success will come and proactive education and providing the support needed to make the process most convenient for physicians desk.
And patients.
What is the appetite from the Paducah extension, our team will be even better positioned for a successful launch for sports income for Iga nephropathy if approved.
Let me now turn the call over to Chris for the financial update.
Yes.
Thank you Peter and good afternoon, everyone I'm pleased with the continued financial strength of our organization, we are well positioned to support our ongoing development programs as well as the upcoming potential launches that could meaningfully change our growth trajectory.
For the first quarter of 2022, we reported total revenue of $53 $5 million, consisting of approximately $58 million and net product sales and $2 $7 million in collaboration revenue from our European in collaboration with CSL before.
This compares to $54 $2 million in their product sales and $14.01 million in collaboration revenue reported for the same period in 2021.
Reported a GAAP net loss of $69 7 million for the third quarter of 2022 after.
After adjusting for noncash expenses and income tax we reported a non-GAAP net loss of $48 9 million for the third quarter of 2022.
On a GAAP basis research and development expenses were $59 $3 million for the third quarter of 2022, the increase compared to 2021 is largely attributable to the continued advancement of the sports betting and pegged about news programs, including increased head count as well as medical affairs activities.
On an adjusted basis R&D expenses were $54 million for the third quarter of 2022.
Relevant noncash expenses for the third quarter included $5 $3 million of stock based compensation and amortization.
On a GAAP basis, selling general and administrative expenses for the third quarter of 2022 were $57 5 million the increase compared to 2021 is largely attributable to launch preparations, including increased headcount and commercial support.
On an adjusted basis SG&A expenses for the third quarter of 2022 were $45 $4 million.
Noncash adjustments for the quarter consisted of $12 1 million in stock based compensation and depreciation and amortization.
For the balance of 2022, we anticipate a modest increase to operating expenses from our third quarter levels and we continue to have a strong financial foundation. We ended the third quarter with $506 $3 million in cash and cash equivalents importantly, we believe this cash balance can support our operations into 2024. This takes into account the extension of our produce.
Into the first quarter of next year the potential for further competitive dynamics for <unk> investing in sports and launches for both Iga nephropathy, and <unk> advancing pegged to that news as well as the milestone payments, we expect to pay related to regulatory achievements for sports betting and talked about news.
I'll now turn it back over to Eric for his closing comments Eric.
Thank you Chris.
With confirmation of our new Paducah date, and the ongoing CMA review process in Europe . We believe we are well positioned for <unk> to become the first non immunosuppressive treatment approved for Iga nephropathy in the U S and Europe .
With the added time afforded to us by the extension in the U S. Our experienced commercial and medical affairs teams will be working even more diligently to enable <unk> to become a new treatment standard if approved.
In parallel we will look to add to our sustainable growth with the upcoming readout from the duplex study presented at <unk> in the first half of next year and the continued advancement of it takes about this program towards a pivotal study in 2023, let me now turn the call over to Naomi for Q&A Naomi.
Thanks.
Thank you Michael.
If you would like to ask a question. Please signal by pressing star one on your telephone keypad.
If you are using a speaker phone make sure. Your mute function is turned off to allow your signal to reach our equipment.
Again press Star one to ask a question.
We will take the first question from the line of Maury Raycroft.
With Jefferies. Mr. Ray Cross your line is open.
Hi, Thanks for taking my question and congrats on the update.
Starting off wondering if you could talk more about what your proposed Rems plan is and talk more about the recent examples that you've learned from which Julia mentioned.
Lastly, do you have evidence that would support less frequent rent testing such as every three months. If you can talk about that.
Sure Great question. Thank you for that well I'll, certainly turn it over to Julia to provide a bit of detail on the proposed rems and what we've learned from other revenues, particularly those within the renal space.
What I would remind you and everyone is that the Rems that is submitted is still proposed we do not yet have a final rems designed and agreed with FDA, nor do we have the final label, but with that in mind drew I'll turn it over to you to provide a bit more detail on those questions.
Yeah. Thanks, Good morning, So we submitted back monitoring thats consistent with how we monitored within our phase III studies and as a reminder, we monitored quarterly within our trials and this was effective and we didn't identify any cases of concern of liver injury. We do know there is another number of other analogs less that are within the rare nephrology.
Space with regards to liver monitoring we know till that pan.
And there's a cadence of different levels of monitoring that has been done from a slightly more frequent monitoring, which then then tends to decrease over time.
I'll also point out that there's a number of agents that nephrologists are familiar with that.
We're quite aware of like MMF, that's used within the patient population that are familiar with rents processes and Esa and then some other in the transplant pace.
Space, and importantly that Hasnt impacted the utilization of these agents and really they are important for education of the nephrologist their practice and the patient and ultimately our goal is to make it convenient and effective.
If you find that your question has been answered you may room remove yourself from the queue by pressing the star key followed by the digit too.
And we'll take our next question from Greg Harrison from Bank of America.
Hey, guys. Your line is open.
Hey, guys. Thanks for taking our question.
First one is.
Do you have a sense on whether the slip on them.
Chemistry has anything to do with FDA is deliver risk for certain.
Great. Thanks for that question and no we are.
Not aware of any length that the FDA is looking to make there. We are aware of some misinformation about sports center. In this regard that was circulating following a regulatory update two weeks ago.
The FDA has not in any time during our review of NDA or in our interactions mentioned anything related to the chemical structure or is the <unk> group being related to.
The need for liver monitoring or the risk of.
Liver damage what they did raise however, really is two important aspects and then making this decision. The first is the need for additional monitoring based on the potential class risk within agents that block endothelin.
And the other is an evolving data set or sports center under accelerated approval and that was really the rationale not not based on what.
What has been sort of a hypothesis that arose about 20 years ago with the first approval of an array.
Weather.
Liver damage risk was associated with the Sulfonamide group, what we do know now is that it's much more multifactorial, but this hypothesis has not really been proven out.
Most importantly, there have been no reported clinical diagnoses of sports center and related liver injury in the program to date.
Okay. That's helpful. Thanks for that and then one follow up.
Do you expect.
There will be any similar liver monitoring requirements and ex U S geographies and if so.
Could there be any change to your timing assumptions.
Sure. So we certainly have looked at what other agents.
In Europe have for their label as well.
Central monitoring and I'll ask bill to cover what we've learned thus far.
Certainly Eric our marketing application in the EU.
Emma was recently accepted for review so we haven't engaged with active discussions with EU reviewers at this point. So we don't know their perspective on potential monitoring for liver enzyme elevations. If you look at the process in Europe , They don't really.
An analog to ramp they take.
A little slightly different tack, where they focused predominantly on education.
So what we will be able to assess this in the future as we get more interactions with the EMA.
Got it thanks for taking the question.
Thanks, Greg.
Yeah.
We will take our next question from the line of Joseph Schwartz from S. VP Securities.
Please go ahead.
Great Hi, Al. This is will on for Joe. Thank you for taking our questions today and congrats on the continued progress this quarter. So I guess one for us to start now with the addition of the liver Rems and we expected black box warning. Some may view, the perceived risk benefit profile of our sentiment has changed a bit so.
Have your assumptions of the addressable market also changed and do you still expect that similar kind of demographic to be addressable at the launch. Thank you.
Yes.
Question will and I would say that based on our assumption that has not changed and I.
I need to caveat. This by we've not seen the final label, but based on what we understand and how others are labeled for liver monitoring we do not believe that our calculations of addressable population that Peter mentioned in his prepared remarks, we will change, but lost Peter to comment a little bit more about how he and his team are thinking about the potential.
Opportunity upon approval.
So hardly Eric and things will for the question.
It's important to realize that this is a rapidly progressing patient population with limited treatment options.
Unmet need remains high, especially for a product was the nonpayment of suppressive profile that is demonstrated to reduce proteinuria was nearly 50%.
As you may have seen over the last few years research has consistently called out the Nephrologist correct our symphony as the most desirable product in development.
So within that context, if you look at the liver monitoring within the Rems I think theres. Good analogs out there in July was talking about that have made it convenient for patients and physicians.
These products are more successful in their commercial uptake.
So we believe that the profile of Sportscenter and remains unchanged and it has the potential to become foundational treatment for Iga nephropathy patients.
Rents may take some additional.
Educational and logistical efforts and that May have some impact on the initial uptake because we are further informing ourselves what it could look like but most importantly, we have the experience with our hubs and patient services infrastructure to provide customized patient solutions that will support the rems implementation.
And it's also good to realize that many progressing patients see that nephrologist on a quarterly basis and quite often even monthly and could you loss really upon it in the script updating lab zelle as a standard practice to inform these patient visits.
Great. Thank you and then if I could just sneak in a quick follow up here looking next year to the early days of the launch.
Are there any analogs for kind of the gradual uptake you might expect with the liver monitor it and how are you thinking about the overall cadence for the first year. Thank you.
Yeah, Peter why don't you take that one.
Yes, I think July was mentioning full of up Tom I think that's a good envelope in in rare nephrology. There was lots of 2018 has been successful in their uptake, but I think it's a good that's a good benchmark for us.
Yeah, and I think what's important is the work that Peter's team is doing to further refine our assumptions and estimates through market research with our revised target product profile that reflects liver monitoring. So we will be able to provide a bit more detail on that in the future, but I think as you pointed out we've been focused on the analogs.
It does it does suggest that long term, we will be successful it can be successful at the launch, but as Peter mentioned, it's going to take.
A bit of education upfront and we want to be cautious just in assuming that that could lead to slightly.
More gradual uptake to begin with.
Okay.
We'll take our next question from the line of Carter Gould with Barclays.
Please go ahead Sir.
Hi, This is Justin on for Carter. Thanks for taking my question and congrats on all the progress I'm wondering if you can provide sort of a rough estimate around the number of patient years worth of data you have for patients that have been treated with <unk> and related to that if there is sort of a hurdle with thinking about how substantial is that database might need to be to revisit.
The rems requirement down the road.
Yes, Justin Thank you for the question and Julia I will turn that over to you.
Okay.
Okay.
We havent publicly released the amount of patient years that we have what I can say is that we are going to present at ASN upcoming some long term data that we have from duet.
Realize that this is under accelerated approval. So as we release before how much of the data that we have of patients. So under accelerated approval. We don't have the full data set or analysis. So as we said we have 800 patients on our clinical trials half of those are on smart suntan.
As we've said before we have about 1200 patients who've been exposed to spark Phantom, but some of those earlier trials, where patients got shorter duration of exposure than treatment time period.
So some of them may not make sense for a longer duration, so and to your second point of what is it going to take that's going to be a continued conversation of how much data we will need to present over time of course, when we complete. These trials next year, we will have additional exposure from our open label extension study.
Okay.
Plex and protect as they complete and readout next year and Additionally, assuming we get approval, we'll have patients who have gotten commercial therapy to be able to submit that data. So it will be a continued conversation over time.
Okay awesome. Thank you.
Yeah.
Thanks Kristen.
We'll take our next question from Tim Lugo from William Blair. Please go ahead Sir.
Thanks for taking my question.
Jason Gammel progress.
We can run becomes something that is maybe proprietary with the companies they have implemented them for a certain therapy.
I guess what are your thoughts on maybe a runs could dampen uptake could also impact the true value of as far as banking franchise and then maybe can you discuss the possibility of that.
With the Rems program maybe.
A bit different for a certain patient subgroups I'm thinking may be pregnant patients or patients on certain concomitant therapy.
Yes, Tim Thanks for the question and I'd say first well.
We'll be able to assess the full impact once we have alignment with FDA on the final design of the Rems, but based on our.
Working assumptions to date, we believe that it shouldnt have.
And major impacts.
On the uptake or the impact on practices.
And I think as Julie alluded to what we see is that whether it's monthly or quarterly does it very much aligns with how many of these patients are being treated for their condition anyway.
And I'll turn it over to Julio on the rest of the question.
Yeah, just to clarify Tim with your question around how theyre going to monitor for embryo fetal toxicity can I get a clarification on that and subgroups.
Yeah, I guess so.
Just any sort of different monitoring certain subgroups versus others, and maybe how that could alleviate FDA concern with you.
Pregnant patients versus <unk>.
Broader monitoring.
Okay.
Okay.
Well, let me clarify that everyone's going to have to sign up for embryo fetal toxicity and this is a consistent thing that is done for all patients to confirm their reproductive potential so across the ear re class every single participant will have to sign up and document that.
You cannot confirm what their reproductive potential is going to be and there's education around that upfront when they get a prescription it's pretty simple in the attached to it.
And then there is a monthly pregnancy testing thats done for people, who can become pregnant and this is across class.
Okay alright, thank you.
Yeah.
We'll take our next question from the line of Lisa Bay Coe from Evercore ISI.
Please go ahead ma'am.
Hi, there. Thanks for taking my question can you talk about.
You're planning a final data.
Final data with the Egfr endpoint.
Might have that.
Thank you.
Congrats.
Some of the concern.
Yes, my pleasure.
Got it.
Okay. Thanks, Lisa.
A little bit.
Difficult to hear so let me just confirm youre asking for confirmation of the two.
Timing of the final data from our trials as well as what our expectations are about those data, including Egfr addressing any questions from the FDA is that right.
Yes, sorry, I'm on a plane and then.
Okay.
That's all right well, thank you for joining the call.
Yeah I think.
We are on track as we've guided throughout the year that the final data from duplex will be available in the first half of next year and then the final two year data from protect will be available in the second half of next year and as we get closer to bringing the data sets in house, we'll be able to further refine.
And the timing, perhaps in a tighter window, but we are on track for it for delivery of those datasets and we'll certainly work.
Diligently to package those for submission to the FDA both for full approval.
For Iga nephropathy for full approval has been S. NDA for F. S. Geos, but also in assessing the safety data to assess the potential for any adjustment or removal of liver monitoring as part of the reps. So I think we'll be able to make further kind of assessment.
Once we see those data and have further conversations with with the agency, but at this point I think thats certainly our intent and the plan for next year.
And can you remind us on the size and duration of the database.
Okay.
Sure and I'll turn that over to Julie.
The size and also what what date it will be part of that.
Mission.
Yes, certainly so for duplex recall that we have about 370 patients who got randomized to active treatment versus far suntan. So we will have that.
And realize that patients are eligible to roll over to active treatment with <unk>. Once they complete the two year trial. So we will have patients who have rolled over for additional data for the protect trial. We have about 404 patients who got randomized to <unk> versus active control and again similar.
Study design that the patients who got Irbesartan will then roll over so we will have additional exposure in those open label extension, where patients rollover to active treatment. So in totality roughly about 800 patients and again, we had significant patients in the early days of hypertension, where we have patients but shorter.
<unk> of exposure in some of those early studies and then Additionally, we have the duet study, which has about 108 patients who got exposed to different different doses and we have patients who have now been on treatment for really up to almost seven years now.
Great.
Looked at other packages that other companies have filed to get.
The levers that seem to move like what size of.
And what duration.
Are you seeing out there.
Okay.
Yes.
Yes, it's difficult to say I think particularly because within this instance, we know that FDA and the cardio renal division is looking through the lens of a subpart H accelerated approval. So we haven't heard anything with regards to a particular threshold or number of patients, it's really particularly based on.
An evolving data set within the diseases that we're studying so I think if we do certainly find this point further kind of insights we will we will share those as we've tried to do along the way, but I think the other aspect that I would just remind you Lisa this is rare disease and the others.
And non rare and worst submitted for full approval. So I think it is.
As a unique situation that we continue to navigate and certainly we'll provide FDA with the with a much more complete data set when they are finished next year.
Thank you so much.
Thank you.
We'll take our next question from the line of Laura Chico from Wedbush Securities.
Please go ahead ma'am.
Hello. Good afternoon. Thanks for taking the question I wanted to follow up on one earlier comment.
I think I heard I apologize if I if I didnt hear this correctly I think you said you are at.
For Sinton is showing ALC ASD elevation that were comparable to Irbesartan and studies.
If I recall correctly irbesartan rates of ALC ASD elevation to take our low single digit.
I'm not sure if that's correct, but wondering is it comparable in terms of the rates incidence or in terms of the magnitude of increase or is it both with respect to as far as setting and then I have one quick follow up.
So we collected it with regards to rates of increases because that was our pre specified adverse events of interest and that adverse events of interest with three times. The S. T. A L elevations, which we monitor it prospectively.
And also submitted to our D SMB for monitoring and that's what we've released that with similar between the two arms in comparable.
Got it Okay, and then I apologize if you have not disclosed this but can you confirm where the elevations you've observed so far with by something in the <unk> setting or has this been <unk> dose patients. Thanks very much.
Across the trials.
So we've looked at it in totality.
Got it thanks.
We'll take our last question from Ed Arce from H C. Wainwright. Please go ahead Sir.
Yeah.
Great. Thanks for taking my questions and congrats on the progress in the quarter.
A couple of questions from me Firstly, I just wanted to confirm sort of some.
Perspective share here today on the call.
With regard to.
The liver monitoring and the Rems.
As you said you take.
Taken a second fresh look now over the last couple of weeks.
Some analogs.
And the history, there and I think you said you had said that really you don't expect.
As others haven't any impact to utilization ultimately.
Question is couple of weeks ago. When you had mentioned and I think you mentioned earlier today.
A more gradual uptake as your impressions. So I just wanted to clarify that although the longer term remains sort of unchanged.
Youre really more focused on the initial uptake part that could have.
A little more gradual uptake.
And then I would call it.
Thank you Ed for the question and that is a correct assessment that we've made we believe that the.
The need for.
Liver monitoring and Rems does not change the addressable population nor does it change the clinical profile of <unk> or the unmet need but we do recognize that this will require some additional education of nephrology practices.
As well as just having our clinicians and patient sign up initially.
And so that we do believe is going to have that impact short term, but certainly long term. We believe that that is not going to be an issue and that's really what we've what we've gleaned from from others, who have launched successfully with the reps.
We had mentioned previously we will continue to refine those assumptions and provide any guidance. Once we have completed the market research to make sure that we have a contemporaneous view.
Of our launch assumptions.
Okay understood. Thanks for that and then secondly, just turning to <unk>.
What are the barriers the SBA is considering before accepting told him assisting as the pivotal study primary endpoint.
And what gives you confidence that ultimately would be successful.
Securing that.
And in that regard does the sixth cohort data from compose.
Play any role in that thank you.
Yes. Thank you for that question, particularly on picked about Nathan as we closed out October which is Thomas cystinuria awareness month.
One that we recognize is certainly.
Community that has a high unmet need and I think that's really driven our desire to have a biomarker endpoint, which will facilitate.
The answer to the next phase of development I'll ask bill to talk a little bit about what that might entail and what we what we believe FDA may be looking for there.
Certainly we've gone through several interactions with the agency discussing the utilization of <unk>.
Total home of 16 as an endpoint, we believe that we've gotten agreement there.
From a big picture view of using total homeless sustain as the primary endpoint in our phase III pivotal trial, but what we haven't completed and as important detail.
Is the are the specifics of that trial and how you utilize it.
Is that endpoint as a threshold or a percent reduction the overall design of the trial that work.
We're still working on at the agency and having received breakthrough therapy designation.
Designation, we have multi disciplinary meeting coming up.
Before the end of the year and then subsequent interactions are a little bit easier to have under breakthrough. So we look forward to having those discussions.
Asked also about the sixth cohort.
That is testing a higher dose as well as the lyophilize formulation.
So we need to see the data in order to.
Make a final dose selection and to confirm.
The safety and Tolerability of the Lyophilize formulation as opposed to the liquid formulation that was in the earlier. So it's on the path to phase III, but it is not gating to further discussions around trial design.
Great. That's helpful. Thanks, so much.
Thank you Ed.
That concludes today's question and answer session. At this time I will turn the conference back to MS. I can bomb for any additional or closing remarks.
Yeah.
Great. Thank you to everyone for joining us this afternoon to learn about severe Jason update.
Fighting milestones ahead, and look forward to sharing more updates along that along the way have a great rest of your day Bye bye.
That concludes today's conference. Thank you for your participation and you may now disconnect.
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