Q4 2022 Travere Therapeutics Inc Earnings Call
Thank you Rachel good afternoon, and welcome to <unk> Therapeutics fourth quarter and full year 2022 financial results and corporate update call. Thank you all for joining US today's call will be led by our Chief Executive Officer, Dr. Eric Dubai, Eric will be joined in the prepared remarks by Dr. Giulia and Rick are.
<unk> Medical officer Al <unk>.
Peter <unk>, 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 matters that are not historical facts are forward looking statements within the safe Harbor provisions of the private Securities Litigation Reform Act of 1995.
Looking statements are not guarantees of performance they involve known and unknown risks uncertainties and assumptions that may cause actual results performance and achievements to differ materially from those expressed or implied by the statements. Please see the forward looking statements disclaimers on the Companys press release issued earlier today as well as the risk factors section in our form.
10-Q, and 10-K with the SEC and.
In addition, any forward looking statements represent our views as if only the date such statements are made February 23rd 2023, and <unk>, specifically disclaims any obligation to update such statements to reflect future information events or circumstances. During today's call, we'll be covering certain financial results for the quarter and for the year.
Ended December 31st 2022, including certain non-GAAP financial results. Please refer to the company's press release issued earlier today again, among other things a reconciliation of the differences between the non-GAAP financial results and the most direct comparable GAAP financial results you can access the press release on our website at <unk> Dot com.
That let me turn the call over to Eric Eric.
Thank you Naomi and good afternoon, everyone.
22 was a year of many achievements that have further strengthened our position as a leader in the rare disease community. This is grounded in our mission.
To identify develop and deliver life changing therapies to people living with rare disease throughout last year, we advanced our pipeline prepared our organization for launch and continue to reach the patients that currently rely on our approved medicines, perhaps most importantly, our work culminated in the recent accelerated approval of <unk> for the reduction of proteinuria.
Adults with primary Iga nephropathy or I can.
Risk of rapid disease progression so.
So as far as the first and only non immunosuppressive medicine approved for <unk>, which has demonstrated a threefold superior proteinuria reduction compared to a standard of care Irbesartan.
As you heard us talk about on a recent approval call we have high aspirations for Phil sorry, as we believe it will become the foundational treatment option for <unk> patients who are at risk of rapid progression.
Importantly, we have the deep market insights the product profile with <unk>.
And the strategy to achieve that goal.
If we are successful we will be able to positively impact many patients in the U S. With this important new medicine.
We're only a few days into the launch in the U S. But we're encouraged by the initial engagement with physicians patients and Payors and Peter will go into a bit more detail shortly.
We still have more exciting milestones to come with so far in 2023 be offsetting the margin trajectory in the U S. We are anticipating a review decision from the EMA in the second half of 2023 for the conditional marketing authorization application for <unk> in the treatment of <unk> in Europe .
We will continue to work closely with our partner CSL before throughout the review process.
And we also look forward to the two year data from the ongoing protect study as a reminder, the interim results from this study supported the accelerated approval of <unk> last week as such we are waiting with anticipation of the two year data set which is planned for the fourth quarter of this year.
Based upon the interim results, we believe the preliminary Egfr data available at the time of the interim analysis were indicative of a potentially clinically meaningful treatment effect after two years of treatment.
And that will be able to utilize those data for a traditional approval submission in 2024.
Additionally from Sports Center, and we expect to have top line data from the two year endpoint in the ongoing duplex study in <unk> during the second quarter of this year.
If the results from duplex are supportive of an <unk> regulatory submission, we would anticipate being in a position to submit an NDA in the second half of this year and we'd also target submitting together with CSL before a subsequent variation to our European CMA application by end of year.
This would represent an incredible opportunity for us to help patients with <unk> one of the leading causes of kidney failure due to glomerular disease.
Beyond <unk>, we continue to advance our novel pegged about in these program for classical home assistant urea or H C U E.
Later this year, we anticipate being in position to provide additional data from the ongoing composed study as well as plans for a potential phase III program. After we complete our regulatory engagements forming.
2022, with a remarkable year for <unk> and I am proud of our organization's accomplishments and perseverance to ultimately get us to our first approval from our pipeline of therapies targeting rare diseases.
We have started off 2023 with a key milestone that has been years in the making and we have much more to come as we continue working towards our mission of delivering life changing therapies to people living with rare disease. Let me now turn the call over to Julie FERC clinical update July .
Thank you Eric and good afternoon, everyone.
As Eric stated 2023 promises to be an exciting year for <unk>, the rare kidney community and the patients and families impacted by IGN, we could not be more pleased with the recent accelerated approval until sorry.
This milestone has created momentum and IGN community and set the stage for many exciting developments to come.
It is important to remember that <unk> is the most prevalent primary Maryland nephritis worldwide. It.
It is often uncontrolled and as a result, it is a major cause of kidney failure and.
In fact high risk people living with ICANN based on median time to kidney failure of approximately 11 years.
Along the way, many great pain, and debilitating fatigue depression, and anxiety and challenges with keeping up with everyday workplace.
Patients and their nephrologist are desperately seeking new treatments that can effectively reduce proteinuria and be utilized long term with less concern for limiting side effects.
Now that's limited to ace inhibitors, or angiotensin receptor blockers, which more than 50% of patients don't respond adequately to and <unk> inhibitors, which are less effective at reducing proteinuria.
Steroids are also available but are generally reserved for more severe <unk> patients because of their challenging safety and tolerability profile.
Bill sorry is the only once daily oral non immunosuppressive medications.
<unk> for the reduction of proteinuria and igen.
As the first of its kind dual endothelin angiotensin receptor antagonist pillsbury targets, two causal pathways critical to IGN disease progression.
In the protect study we observed a rapid sustained and three times greater reduction in proteinuria compared to Irbesartan.
<unk> is showing a consistent and tolerable safety profile similar to Irbesartan.
We are thankful for the Fda's accelerated approval of Pillsbury and are proud of the label, we have received which highlights the strongest clinical data demonstrated in a head to head phase III study in <unk> to date.
I encourage you to review the entire label, that's a flurry of dot com to further understand the clinical performance safety profile and the Rems process.
A point worth noting is that both the liver and pregnancy runs monitoring can be obtained with a single blood draw.
Since high risk patients typically undergo monthly medical visits and lab, we expect the integrating rems monitoring into their current course of care will be seamless and serve as an effective tool for physicians monitoring their patients.
Overall, we believe this label will provide nephrologist with the confidence needed to prescribe <unk> for their <unk> patients at risk of rapid disease progression and that this is just the beginning for realizing so far its potential.
Later this year, we're expecting top line data from the confirmatory portion of the protect study.
If these data demonstrate a clinically meaningful benefit on Egfr. After two years of treatment. This will further solidify <unk> potential as a new treatment standard.
Achieving this would enable us to submit for traditional approval with the expectation of a label that would be more representative of the total population studied and protect and reflect the long term benefits of so sorry.
Beyond <unk>, we are nearing the topline results from the duplex study of <unk> and <unk>.
The duplex study is progressing according to plan and we're pleased with the continued conduct and efforts to get to database lock.
If the two year data progresses in a favorable manner, we expect to submit an NDA for <unk> to gain an indication for <unk> and be added to the <unk> label.
We would also look to submit a variation to our PMA application if approved for <unk> in Europe .
This can be paramount for people living with <unk> as many are facing an even faster progression to kidney failure and fewer effective and safe treatment options.
Beyond <unk>, we continue to advance our <unk> program in classical Hamatsa scenario during.
During the fourth quarter, we completed enrollment activities and the sixth and final cohort of the ongoing phase one two composed study.
As a reminder, <unk> demonstrated dose dependent reductions in total homocysteine during 12 weeks of treatment and compose.
And the one five milligrams per kilogram twice weekly dose cohort treatment with <unk> resulted in a rapid and sustained reductions in total <unk> of approximately 55%.
Resulting in maintenance of total Homo sustain below a clinically meaningful threshold of 100 micro mills from week to week 12 of treatment.
Our sixth cohort evaluating one additional higher dose and also a <unk> formulation that if effective could be utilized in a potential pivotal program and the commercial setting is approved.
We remain on track for additional data from composed later this year.
These data will be helpful for completing our engagements with regulators and potentially initiating a phase III study in the second half of this year.
Finally on the development programs, we received fast track designation for our <unk> development program in 2022.
As many of you may recall keynote <unk> is currently approved for the treatment of radiolucent gallstones, but it has been recognized as the standard of care versus Ribeiro tenderness, xanthomatosis or CTX for many years.
Our ongoing phase III restore study is designed to provide a dataset that will allow us to submit an NDA to have the label amended to reflect what we believe is the true use of the product.
We believe this could significantly aid patient identification and help people living with CTX gain earlier access to are greatly needed treatment option.
We know that if CTX is identified and treated early oftentimes patients can go on to live a relatively normal life.
We expect to have data from the phase III study in house this year and subsequently submit an SDA if the data are supportive.
With that I'll turn the call over to Peter for the commercial update including additional color on the feels very much Peter.
Thank you Ron.
This has already been an exciting week for us.
Mr from Nicole Australia rebuilt our fuel volume.
Commercial infrastructure, we have delivered consistent results over the past eight years.
We further strengthened our execution capabilities and now have a dedicated loan fee was a specific experience and expertise to be successful, we still still summary.
I mentioned the <unk>.
<unk> was really to execute with a sense of urgency and I'm pleased to report our team has been executing very well since approval Friday afternoon.
Within one day.
The materials were finalized consistent due to lead in the field.
<unk> and <unk> websites when life and operational.
Even though it was a public holiday our commercial field teams were excited to finish the three you get out into the field engaging with their customers. Both nephrologist is real estate.
There will be extensive planning and execution efforts led to the first fuel sorry prescription being written with you ate business hours of approval.
We anticipate this positive momentum to continue to build.
To provide you a bit more complex on our initial base fulfill saia commercialization.
Our experienced commercial field team of more than 80 seasoned professionals is engaging in productive conversations with nephrologist and players.
Focusing on the boardwalk diseases.
The challenges with current standard of care in how it feels far disposal could potentially address the shortcomings in the addressable population of patients at risk of rapid progress.
Yes.
The receptivity and initial interest from the Nephrology community is in line with our expectations.
Simplifying the patients have been waiting for Lakefield snobbery.
Prior to approval Nephrologist have consistently expressed that they use more efficacious treatment options that allow for long term use in treating patients who are at risk of rapid progression without the tolerability issues of immune suppressed immunosuppressive agents.
We believe feel sorry is well positioned to fill that need.
Yes Brooks. Thank you. Thank you.
Consistent with full control of this has been doing over the past 30 years.
So its built upon a common beliefs and routine.
But as the missing component cost and recognizing the Endothelin payloads.
And we know that the endothelium and then get them stimulate each other impacts in tandem to amplify them through the filtration barrier.
We sold these increased both newly levels.
Thank you Robbie blocking Endothelin and then get into we feel sorry.
LOE for the superior efficacy relative to herbicide zone.
In the interim readout on the landmark protect trial.
Based on Salesforce locomotive issue and robust efficacy and safety data. We are convinced that <unk> has the potential to become the foundational treatment option with a roughly 30% to 50000 patients are addressable into the current indication.
It is our goal to make sure the cornerstone therapy for these patients within the evolving treatment paradigm.
Lastly, I mentioned on the approval that we have learned from recent product launches and revenue flows and if we know the nephrologist have largely mechanism and data driven.
Therefore, our initial focus is to educate nephrologist, who feels slightly profile, both the efficacy and safety findings as outlined in the label to.
To give them a solid understanding wholesales far you may help them rapidly progressing patients.
But other launch then I think that we will be navigating is the process of getting to payer coverage.
I believe we are also off to a solid start.
Prior to approval, we have already conducted scientific preapproval engagements, which they are still bring over 150 million months and we are building those initial conversations mode.
This week, we have already interacted.
With several Mitchell National Payors and these interactions have reinforced the pace generally well aware of the birds Mcbride and appreciates the importance of proteinuria reduction in relation to disease progression.
Last week I also referenced the <unk> plan for exquisite first you'll start experience for patients and physicians.
We have established for the year total care to help patients by offering personalized education.
Before in the reimbursement process and copay assistance for eligible patients.
<unk> also assist patients and physicians with the Rems enrollment.
Typically the simple procedure.
During this process decisions will review the prescribed and ignored the understanding of the label.
Then they will be prepared to prescribe <unk>.
It is also worth emphasizing that our and smoothly integrate seamlessly with the established ramp processes nephrologist.
We used for other therapies.
From a logistical standpoint, we remain on track fulfills Barak can be shipped to our specialty pharmacies next week.
In summary.
Our loan execution historic According to plan and we are well positioned to deliver from our powerful purpose greenfield <unk> to patients who need it most.
Turning to the performance of our in line product portfolio in the fourth quarter 2022.
I continue to be very pleased with the execution of our commercial organization.
We.
We need to see solid demand as we have further supported identification and treatment of cystinuria patients.
This is a testament to our organization's patient inspired way of operating and our established capabilities in the rare kidney space.
At least was the meaningful viola performance within the evolving competitive landscape.
As we have talked about historically.
We are seeing the impact of generic dynamics that affect net sales of Iowa, and we expect to discuss with you.
We realized further this year.
Hello, bile acid portfolio continued to deliver solid growth in the fourth quarter.
The global team has a long standing reputation with performance and dedication to educate pediatric analysis can help apologies.
These efforts have been key to <unk> continued growth.
Our team's capability to help physicians and patient identification.
Ultra rare conditions is fundamental.
This expertise provides a solid foundation to build upon as we prepare for potential future CTX indication bookings at all.
As we progress the <unk> development program.
In 2023, we expect to return to year over year growth in net product sales.
Well, we expect further pressure with viola, we anticipate that this will be offset by the expected growth of mobile asset portfolio in the first fully launched performance.
As a reminder.
We anticipate that Youll stars performance will be in line with reasons ran flawlessly benchmark in the first six to nine months.
And once we gained meaningful fuel vehicles.
And prescribers gain the initial experiences.
The same consistent proteinuria reduction observed in the protect trial, we anticipate accelerated adoption towards the end of the year.
Beyond this first year, we are well positioned for ongoing growth of Youll Slattery, which is exemplified by our ability to execute as demonstrated with our commercial performance in 2022.
This together with the high end Mathieson IGN.
Robust profile feels fine and our meaningful timing advantage before additional therapy.
This may potentially be approved gives us confidence that we will succeed in our strategic objective to make fuel sorry, the foundational treatment for rapidly progressing patients.
Let me now turn the call over for Chris for the financial update.
<unk>.
Thank you Peter and good afternoon, everyone with the continued execution of our commercial organization and our focus on our key priority throughout the business. We ended 2022 and a strong financial position for the fourth quarter of 2022 net product sales were $52 3 million compared to $54 6 million for the same period in 2021.
For the full year 2022, net product sales were $205 million.
Compared to $210 8 million for the same period in 2021. The difference is largely attributable to a decrease in diode sales, partially offset by an increase in sales for the company's bile acid products.
Research and development expenses for the fourth quarter of 2022 were $60 2 million compared to $62 2 million for the same period in 2021 for the full year of 2022, R&D expenses were $235 8 million compared to $210 $3 million for the same period in 2021. The difference is largely attributable to the continued advancement of.
The Companys first that in fact about next clinical program, including clinical trial expenses manufacturing and increased head count.
On a non-GAAP adjusted basis, R&D expenses were $54 2 million for the fourth quarter of 2022 compared to $57 7 million the same period in 2021.
Selling general and administrative expenses for the fourth quarter of 2022 were $62 9 million compared to $42 $1 million for the same period in 2021.
Full year 2022, SG&A expenses were $222 million.
Compared to $149 9 million from the same period in 2021. The difference is largely attributable to the commercial launch preparations peripheral sorry, including having the full sales team on board and ready to launch this week.
non-GAAP adjusted basis, SG&A expenses were $50 2 million for the fourth quarter of 2022 compared to $30 9 million for the same period in 2021.
Total other income net for the fourth quarter of 2022 was $1 1 million compared to total other expense net of $4 $4 million from the same period in 2021. The difference is largely attributable to increased interest income and lower interest expense during the period.
Net loss for the fourth quarter of 2022 was $65 8 million or $1 <unk> per basic share compared to a net loss of $51 6 million or <unk> 84 per basic share for the same period in 2021.
For the full year 2022, net loss was $278 5 million compared to $180 1 million for the same period in 2021.
On a non-GAAP adjusted basis net loss for the fourth quarter of 2022 was $49 1 million or.
Or <unk> 76 per basic share compared to a net loss of $37 6 million or <unk> 61 per basic share for the same period in 2021.
As of December 31, 2022, the company had cash cash equivalents in marketable securities of $452 million.
As we look to the year ahead, we anticipate that our operating expenses will continue to increase and maybe variable quarter to quarter as we advance our programs.
For SG&A. This is primarily driven by having a full year of the expanded sales team in place and their associated launch investments to position thus far it for success.
For R&D is primarily driven by the continuation of both the protect and duplex study as far.
As well as our work to evaluate <unk> in combination with <unk> inhibitors, and preparing <unk> for a potential pivotal program, including building supply.
Accordingly, we anticipate that we can manage our balance sheet to support our operations well into 2024. This takes into account potential further competitive dynamics with Iowa investing in launches for both Iga.
And potentially a first year advancing talked about as well as milestone payments related to achievements for the programs.
We entered the new year with a strong financial position to support this exciting period of launch execution and a continued advancement of our pipeline to a number of key milestones in 2023.
I'll now turn it back over to Eric for his closing comment Eric.
Thank you, Chris I want to express my gratitude to the rare disease community the patients their families and the <unk> team for their hard work and dedication that has led us to the successful moment the launch of <unk>. The strong reception by physicians patients and Payors. Even in these early days demonstrates the value of <unk> address.
The unmet needs.
Of those and the rare kidney community, we are committed to improving the lives of patients and to do so are focused on the advancement of our pipeline. In this regard we still have a number of exciting milestones to come including the potential approval of <unk> for <unk> in Europe in the second half of this year and the two year data from the protect trial in <unk>.
Again, the fourth quarter.
We also anticipate top line data from the two year end points in the duplex study of <unk> in <unk> in the second quarter of this year, which could lead to an important new indication for <unk> and finally, we expect to be able to share more this year on our novel <unk> program as we prepare for a potential phase III program.
Our years of hard work of setup up for an incredibly bright 2023.
I am confident our talented team will deliver strong results for our patients and for the rare disease community. Let me now turn the call over to Naomi for Q&A Naomi.
Thanks, Eric Rachel can we please go ahead and open the lines for Q&A.
Thank you.
To ask a question please signal by pressing star one on your telephone keypad.
We're using a speaker phone. Please make sure your mute function is turned off to allow your signal to reach our equipment. Please.
Please limit yourself to one question and one follow up question and then reenter the queue. If you would like to ask additional questions.
We will take our first question from the line of Greg Harrison with Bank of America.
Harrison Your line is now open.
Hey, guys good afternoon, and thanks for taking the question.
Maybe just to start off could you walk me through the process.
From a patient perspective.
Getting the script enrolled.
Enrolling in the Rems program and then.
The monthly maintenance.
Testing for their ends.
Yes, great. Thank you very much for the question, maybe we'll turn to you first and you can walk through how this fits within how these patients are treated and Peter you could walk through what the process is for prescription and receiving.
<unk>.
Certainly thanks Gregg for the question. So I realize that patients who are at risk for progression are going to see there are nephrologist and more frequently, particularly as you have a change in their treatment algorithm. So they may see them every month with labs and so as a patient is going to go see their nephrologist theyre going to discuss their overall.
Risk of progression, having significant proteinuria as well as their Egfr decline and then for all of this is going to sign up for the Rins and the process for signing up for the Rems is relatively simple from both the physician perspective as well as the patient they need to be educated that's a significant proportion of the rems that means reading the label reading the prescriber.
Pharmacy Guide and then signing up signing up means filling out your contact details and then signing a statement that says youre going to monitor your patient appropriately.
It's the same process for a patient they give their contact details state that they have been informed about the overall risk benefit and that theyre going to follow the process and for a patient what that means is that they're going to get their labs every month, and then theyre going to get the therapy through the specialty pharmacy and then just I'll add one additional detail is we have just a couple of special.
Pharmacies and Theyre going to go through the similar process read the label be informed read the prescriber Pharmacy Guide and then give their contact details and then a test that theyre going to follow that process.
Yeah, let me build on what <unk>.
Thanks for taking my question before giving you a little more details on the mechanistic of vehicle care.
Patient services I think it's good you realized the highest unmet need for these patients and that's the reason why we have accelerated approval interest rates.
You have to realize this is a younger patient population is often diagnosed in the late teens or early twenties.
Half of those patients progress to kidney failure with 11 years and so the Hugo mentioned in between.
Pre remarks slipped me a lot of those patients will.
In dialysis in the midst of depth.
Reductive lunch.
When we talk about the Rems and the early responses, we have seen so far and this is still early days and it's a form of promoting so sorry with <unk>.
So from the fraud is confirmed to date donuts.
Treatment options today for these patients because they have Phil <unk> and Arps and still it is customers moving upstream.
So wanted to just understand efficiency and safety profile of those problems.
They appreciate the simple procedure of Rems enrollments and the focus back to the clinical value that <unk> may have to be patients I think you have talked already about.
Precision as well as efficiency pharmacist will be doing.
But I will also.
I'll say that the median.
We have total care, we provide services to make this process as convenient as possible for both physicians and specialty pharmacies and especially the patients.
Great. That's really helpful and then could you remind us.
How many <unk> patients are treated by <unk>.
Community Nephrologists and how this has influenced your launch strategy.
Yes. Thank you for the question Peter.
Majority of those patients are being treated by.
Community Nephrologist and we've planned for that as well that's why I mentioned in call last week that we will be consistently calling on about 6000 nephrologist too.
To cover about 85% of the patient potential.
Great. Thanks, again for taking the questions.
Thanks, Greg.
We will take our next question from the line of Maury Raycroft from Jefferies. Maury Raycroft. Your line is now open.
Hi.
Thanks for taking the question.
When you did your most are our recent market research at the end of last year and asked about intend to prescribe in six months or one year of launch.
I'm wondering if you tested key aspects of the label in your market research.
Thanks, Mark for that Great question, Peter would you like to take that.
Yes, absolutely.
<unk> for that question.
So we have done consistently.
Market research and the tools and consolidated by external research for example, buy a syndicated market research.
So break it to me like the intent to protect did not change after we announced deliver monitoring ramps.
Intel to prescribed remains 90% and we just did I just saw we sold actually this week.
The latest.
Final label.
Again, the intent to prescribe came in at 88%, so very consistent at around 90% prescription and assertion year.
About 70% intent to prescribe in the first six months, so that didn't really meaningfully changed.
Got it.
Peter you highlighted some of the plans or our Doctor education efforts can you talk about where the most challenging learning curves will be.
How will you message around Egfr to doctors.
Yeah, absolutely I mean, it's.
Early days as I mentioned, it's day four.
What we see so for what I'm hearing from.
Our field reps is there is great excitement for the promise of Joe Slattery.
In fact, I got yesterday from one of our games.
<unk>, who has been in the field for 30 years seeing that scene has never see this level of excitement among nephrologist. So I think there is a certain level of excitement.
To learn about the profile of salary and put an offer in the market depth sufficient a measuring on a monthly basis and also how they monitor the progression of disease and how they change the treatment plan.
So the conversation Egfr had local mafia and many of those conversations I understand it's an ongoing trial.
They're excited to learn more about the show sorry profile overtime.
Got it makes sense, thanks for taking my questions.
Thanks Martin.
Our next question comes from the line of Joseph Schwartz with FCB Securities.
Joseph Schwartz your line is open.
Great. Thanks, so much I have a question on Iga nephropathy, and then <unk>. So how do you expect the rate of fill sparring uptake to differ.
If it all amongst patients treated at academic versus community nephrology centers and beyond those segments are there any other particular physician demographics that you expect to be earlier.
Earlier or later adopters.
Joe. Thank you very much for the Great question, Peter I'll pass that over to you.
Yes, very timely question Joe because this was also part of the market research that I was just referencing so we saw that.
Yesterday.
Interesting Utilizations intended utilization fulfills Fleury is basically similar.
Gross community Nephrologist as it is in academics and focus so we will see how that materializes over time with the intent to prescribe is quite similar among those too.
She will be categories.
Thanks, Thanks, Peter maybe if I could just add Joe one of the things that we.
We are reflecting in our launch plans and Peter's team has done a fantastic job is really helping to understand not just those 6000 per targeting but also this segment to make sure that we recognize who are those physicians that have through their behavior adopted recent innovation more quickly this sort of early adopters.
<unk> versus later doctors and so our team is making sure that we're very much focusing our efforts in the first part of March on those clinicians that we would see as early adopters there similar to many other.
Launches. So I think it's not just about academic versus community, but it is also number of patients and.
As I say behavior such as.
Adoption of recent rare renal launches.
Okay.
Yes.
If I may build on that Eric just mentioned that we would be.
Consistently calling in about 6000 metrology, so maybe to give you a little more context, how we got to those 6000.
It's really based on three different segmentation in sourcing assessment that we did one was based on patient volume.
One was based on behavior in particular on new product utilization to really get to those innovators and early adopters and the third one is an influence on the nephrology community. So we have a very clear way to target and segment.
Are those physicians that we see as most.
Valuable in the prescription process to get to the broad patient population.
Very interesting. Thank you and then for the <unk> G. S data next quarter, how should we be thinking about the bar for success in terms of Egfr difference what is the overlap.
<unk>.
It's clinically meaningful in the bar for approval how does that look.
And do you have any specific guidance from the FDA.
That says what you need to achieve there in order to be able to file for approval.
Sure.
Sure. Thank you Joe for the question I'll turn it over first to you on the clinical relevance of an egfr treatment effect in <unk>.
Where we would see success and then bill you can share insights and expectations from a regulatory perspective.
Certainly thanks for the question I think it is important to note that we saw of clinically meaningful and significant reduction in proteinuria and FX, yes that should translate into a significant treatment effect on Egfr and if you look historically at other trials.
Looking at a difference in Egfr cloud most of them.
<unk> two inhibitor data.
The difference in slope, that's clinically meaningful for showing a long term kidney protection is anywhere in the range from <unk> 75 to one mil per minute difference and so we powered the trial appropriately to show both the clinically meaningful and statistically significant difference based on proteinuria reduction that we've seen today.
And I think Barry Thanks for taking my question.
Yes, I think when I think about it sort of a regulatory for correct.
Yes. This is bill.
From a regulatory perspective.
Lines up pretty closely with what.
As clinically meaningful.
We've seen <unk> was approved with a <unk> 75 difference. So the agency has clearly recognizing what Joel was talking about and.
With a therapy that's treated for years.
A consistent therapy, a small difference in mills per minute as a very large impact on time to progression.
Or if youre looking at time for time to renal replacement or need for dialysis impacts really quite significant even with small differences in egfr slopes.
Thanks again.
Okay.
Thanks Bill.
Okay. We'll take the next question from the line of Tim Lugo from William Blair, Tim Lugo. Your line is now open.
Yes.
Hey, guys. This is lock off Tim Thanks for taking the questions.
First I guess, maybe for Chris I was just wondering if we should expect any stocking dynamics.
In the next month, I guess or.
Much stocking at the specialty pharmacies.
And then second one quickly just we noticed there's a late breaker at WCS.
Can you give any color on what will be presented there will new data that's not in the label.
<unk> and <unk>.
That presentation.
Alright.
Chris why don't you take that and you look and cover WCS.
Sure. Thanks for the question Lachlan so with our distribution model you really shouldn't expect to have any kind of meaningful stocking and really when we get to a stable state here.
We expect it to be somewhere in the range of a week or two weeks at most so not much of a dynamic there to work through at the beginning there'll be a little bit, but not really much of a stable state.
Yes, and thanks, we're really excited to be able to present, our data at W. Fan.
X months, you can expect to see additional efficacy data as well as our safety data.
We will not be releasing our egfr.
As we have agreement with the FDA that we won't release that until we complete the clinical trials.
Really excited to be able to present that.
To nephrology community.
Okay. Thanks.
Thanks, a lot.
Yeah.
Okay.
We will take the next question comes from the line of do Kim with Piper Sandler.
So Kim your line is now open.
Hi, Thank you thanks for taking my question.
A question on the.
Phase III duplex study.
Studying.
<unk>.
When we look at or think about the.
Egfr slope.
The 108 week data readout.
Can we use the duet extension study.
And the slope that was calculated for there as a good estimate.
And when you calculate the slope of the Egfr curve, what time points do you look at I know Ford do wet.
You were looking starting at day 42, two week one O eight.
Just wanted to know where the starting point is.
So thanks for the questions I'd say, we certainly do.
Do you feel that there is a parallel between what we have seen and do well and what we expect to see in how we've designed duplex Youll alternative alternative question to you.
<unk>.
Oh, sorry, I'm getting a little feedback, but I will turn the question to you on how we might expect to see.
The slopes for.
For <unk>, but also perhaps natural history, given that we didn't have long term follow up of our active comparator in that trial.
Yes, I think the long term data that we have with Keefe Bruyette <unk> kidney preservation comparison, we would.
Back to stay in long term for patients who are at high risk of progression with primary FX, Jeff I would say historically those patients can progress more at a rate of <unk>.
Greater than five Mil per minute more like 789, 10 mil per minute per year, and we saw less than that in our long term <unk>.
If our data that we presented last year at ASN and then in particular in patients who achieved complete remission, we saw significant preservation and those patients with regards to long term egfr slope.
I don't know if theres any additional granularity you'd like me to provide around that.
Just wanted to see how the slope is calculated do you look at the slope of the curve from the beginning of the study out to 108 weeks I know, it's not a difference.
A.
Moment in time at week 108.
But just the overall slope of the curve.
You do look at the total debt.
Beginning all the way through the study and and that's what's so great about looking at ESMO.
With every single data point for all patients to look at the trajectory of the curve and.
And we will look at both of which is from the very beginning all the way to the end and waste all the data equally as well as chronic slow which look more at after six weeks to the study and to minimize the effect of the acute hemodynamic effects.
Great that's helpful and a quick question for Chris.
How will you account for the so far a royalty to ly again.
And the income statement.
Thanks for the question.
We will be updating that when we report <unk>. So we're finalizing that now, but we'll make sure that it's clear out to you guys and being able to view the financial statements as to how exactly we're paying that.
Okay. Thank you.
Thanks, Joe.
Yeah.
Okay. We'll take the next question is from the line of Lee <unk> with Evercore ISI.
Please <unk> your line is now open.
Hi, I think most of my questions been answered, but I guess I would just ask.
What's your level of confidence.
For.
A good outcome in the upcoming <unk> final data.
If you can just explain.
Explain that level of covenants that you're highly confident kind of hopeful but moderate.
Not so confident just curious on how you're thinking about getting a ton of questions without best job. These days. Thanks a lot.
Sure, Yes, Lisa Thank you very much for the question. We certainly are excited about.
This upcoming data readout next quarter.
I'd say that.
We remain confident in the outcome and that's largely because the way that we've designed the trial was based on showing a robust and statistically significant.
Superiority on protein area that then would predict out to egfr.
And certainly as we've looked at the way that the trials conducted the number of patients that we retained in the trial all of those things that we look at to ensure that.
The study is being conducted as we had hoped is there alternative over to Julian maybe bill if you have.
Any further thoughts on.
Why we remain confident and really what does good look like coming out of the.
Two year results.
Yeah, I'll just continue on with what Eric was saying.
Today's call and statistically significant separation.
And a reduction in proteinuria, which bar suntan versus Irbesartan and I would say importantly, when we met with the FDA. They said the study is designed can support traditional accrual and so thats also what gives us the confidence that we will be able to achieve what we've set out we powered the study appropriately as Eric said, we continue to have a significant.
Number of patients to be able to achieve our endpoint and we had a separation.
Branch to show the true effect on Egfr.
And we'll also be going under.
Mr. Bill to talk about looking at an S&P AA.
<unk>.
Accelerated provides a very different situation bill do you want to add color around.
Sure I think that when you are in the position.
As the agency on accelerated approval they've demonstrated that they approach it very deliberately and somewhat conservatively because you have a partial data set both for safety and for efficacy at the end of the study it's much more traditional approval. So that's.
Helpful in that we aren't asking them at that point to take regulatory risk and their ability to be more flexible is is there and looking at the totality of the data I think the other additional element.
His last Friday's approval of <unk> story.
We're now looking at an additional indication so drug that's already approved both safe and efficacious. So I think that puts it in a different frame from a regulatory standpoint, when compared with an interim analysis under subpart H accelerated approval.
That's a really good point, thanks for mentioning that.
Thanks Lisa.
Yeah.
Okay.
Okay. We'll take the next question is from the line of Carter Gould with Barclays.
Carter Gould your line is now open.
Great. Good afternoon, thanks for taking the questions I guess, the first I guess the first half is on the top line <unk> data in <unk>.
I guess, how much data is going to be in that in that top line release, or where you're going to have seen enough data that we can assess the clinical significance of that or are you going to prioritize saving that data for a medical meeting and then I guess, maybe alongside that.
Peter when you or Peter and Joel when you think about that data coming out to what extent do you think nephrologist may read through from potentially positive Egfr data in <unk> and <unk> two gigantic potentially pulling forward some of the demand in that launch. Thank you.
Alright, thanks for the questions Joe why don't you take the.
The top line, what the team is thinking and.
Any potential read through and then Peter you can add your thoughts.
Well, it's a great question I mean, we will have a trial thats completed so we're not limited with regards to keeping data.
It's a balance because we do want to have a very high tiered publication and presentation at an important meeting.
But we will be able to release the Egfr data our total whether we give you all the curves and all the additional data we're going to have to make that decision probably pretty soon but at least enough to give you confidence about.
The results of the trial.
With regards to the Nephrologist and the read through I would point through to the <unk> two inhibitor Cana, where we don't necessarily see the same magnitude and treatment effect in one disease versus the other with regards to the endpoint of 40% decline in Egfr kidney failure dialysis and <unk>.
Plants, each disease is quite different and even though the drug you might think should work across the board with regards to one or the other it may not for a number of different reasons, whether it's the underlying disease. The heterogeneity of the patient population studied in other things. So I wouldn't say that there is necessarily going to be.
So from one or the other depending on the magnitude of the treatment effect or.
What we see there.
Eric do you want to make other comments around that.
No.
You said I think it's right those patient profiles are quite different.
The way I think about its garner is really excited though we have this continuous data stream has something continuously to talk about with the physician only.
Only built the excitement for us fulfills primary so it is almost like a continuing loans versus yield data.
New approvals coming into next into next year.
Thank you congrats again.
Yeah.
Okay. We'll take the next question from the line of Mohit Bansal with Wells Fargo Mohit Bansal. Your line is now open.
Thanks for taking our questions. This is Adam on for Mohit.
To say that you're.
Prescribing information for Tomorrow.
Specificity on PCR classes compared to the FDA label pass Nephrology approvals and then separately could you prescriber base be better equipped to do any monitoring is that they would conduct due to greater das practicing in academic centers.
Okay.
Adam Thanks, so much for the question, let me clarify the first question around the label are you asking just the level of detail and data that we have on UPC in our label compared to others I want to make sure that I answer the right question.
No I'm asking for.
Yes.
The approval in Europe that when you ultimately get broken that geography, ultimately whether it have the same specificity on what your PCR ranges on patients you treat that as well as <unk>.
Safety detail essentially it could be heavier in the U S label relative to past years.
Both have looked like.
Okay got it. Thank you Bill maybe we can turn that to you I mean, certainly we won't be able to speak to specifics on the European label, given that we're still in that process, but bill maybe you can give some thoughts on how that labeling may may vary across regions.
Yes, no. Thanks for thanks for the question and you are right Eric It's a speculative answer because we're in process with the review with with EMA.
It's important to realize they're looking at the same dataset.
Filling for one doesn't contain different data from the filing for the U S. FDA NDA.
But they do have differences in how they present data how they treat data for example, there isn't such a thing as a rems.
In Europe , they treat risks in a different in a different fashion.
I think it's we don't have indication at this point in the review of any great differences between the agencies, but it's too early to really be definitive on anything so we look forward to that.
Updating you on that in the future.
Peter do you want to take any thoughts on the.
Okay.
Any difference in practice based on patients being seen more predominantly in academic centers in Europe , and how that might play out.
Having had the experience to be in Europe is the European I think that is generally right I mean, it depends country by country.
I think we send it to scale.
I think generally it's more established in Europe , I think overall, you see higher egfr levels for patients that are being referred to to Nephrologist nothing.
That is generally right because it depends very much mark to market.
Yeah.
Yeah.
Okay. We'll take the next question from the line of Laura Chico with Wedbush Securities Laura Chico. Your line is now open.
Thanks, very much for taking the question I've got two one first on the clinical and I guess, our own market research has shown about 20% to 25% of <unk> patients are now receiving <unk> two inhibitors and I'm not sure if jeweler Peter could comment.
Of the patients that are on an <unk> two inhibitor what proportion of those remain over a gram on proteinuria.
Alright, I would like to take that question.
Maybe just to kick that off and Laura I think your mortgage research signings are quiet.
Consistent to what we have found as well.
I think one of the important things to mention is what Julie mentioned on the call earlier as well.
<unk> two has the outcome data, but it does not have the profound proteinuria, reducing the thickness Jill slattery.
And the Nephrologist I have been speaking to as well as what we saw in market research data.
We're very excited about the complementary mechanism <unk> sources SDLP do.
I'm very excited about a novel new suppressed a combination approach that.
They may have now.
And Additionally, I think also in Georgia and talk more about it as a complementary profile of <unk> with regards to sodium excretion in the diabetic.
July from Florida saw Kevin can speak in more detail.
Yes, I would agree with that.
Use them in concert.
The most interesting combination that there they're interested in using together is.
<unk> inhibitors, plus <unk> due to the complementary mechanism of action of SDLP tiers, but don't know how their kidney protective exactly but you do have the tubular merrell or feedback that helps to enhance sodium excretion and we know that <unk> has a direct benefit on the glomerulus the prototype the tubular interstitial.
To have that kidney protection, reducing proteinuria and the magnitude of proteinuria significantly greater with suntan all the proteinuria data that we have with <unk> other than anecdotally when you talk to a nephrologist of where they get their patients. All the trials were done in patients with low levels of proteinuria less than a gram.
I mean, if you look at that apathy, turning your amp a kidney they were relatively low levels. So there they tend to be used in kind of later stage in general. So we don't have the more high risk patient profile to tell you what proportion that under a gram, but I think the vast majority of theyre going to need combination therapy to really get them to.
And where we want that lessen the Graham and even further that complete remissions patient, where you can get them under than three grams to get them to that really lower risk patient profile.
Okay.
You talking through that.
Sorry, Laura it might be worth Julia just speaking to some of the data that we would expect to have next year from that from the studies that we have because I think.
It would be useful to be able to see those data from in a clinical setting.
And the trials that we are doing.
Yes, I think Laura we already do have a drug drug interaction that shows that we can safely combined and then additionally, we're going to have two types of combination study, one where you've got patients on <unk> and <unk> inhibitor and the other in the opposite direction, where patients are on an <unk> inhibitor and we add our fintech.
And we will have safety data and we'll have primary and efficacy and then Egfr data and we will have information on that next year.
Well certainly we're looking forward to that and then maybe one follow up question on the financial Chris I heard you mentioned cash runway well into 'twenty four I believe I heard correctly could you talk a little bit more about the flexibility on the balance sheet for extending runway I know there is a milestone payment there too.
Ligand in Bristol, but any other inbound milestones that we should be considering in terms of our modeling.
Yes, thanks for that question, Laura So when I think about the balance sheet and specifically to the milestones.
Have some that would be coming in potentially for things like regulatory approvals in Europe .
And then also we will have some coming out for things like pegged about advancing right. So there may be a net effect of those and when I think about the balance sheet overall and when we look at cash burn there certainly as flexibility. There's a number of things that go into our estimate there and we've commented in the past where we take a conservative approach right, we're taking into into account.
Potential for further.
Generic erosion fourth aisle, we're taking into account all of the investments needed for positioning thus far I appropriately for again, an FSP has launched et cetera. So there certainly is some flexibility in that but we're trying to give you guys. A good view as to what we expect to use our operations going forward.
Thanks, very much guys.
Thank you Laura.
We will take the next question from the line of Alex Thomson from Stifel. Alex Thomson. Your line is now open.
Great. Thanks for taking my question, just maybe a quick follow up on <unk>.
<unk> inhibitors I guess at this stage in the launch and based on some of your initial conversations with payers what has been the receptivity with covering pillsbury on top of <unk> prior to the new clinical data and Youre going to generate next year. Thanks.
Alex Thanks for the Great question, Peter would you like to take that.
Yes, I think Alex.
Early days to comment on that but I think we have had quite some pre approval conversations with payers.
The.
Took away from that is that payers are not anticipating to have like a step through.
With <unk> two a deal to do has a broad label is both for diabetics and Mumbai.
C J D.
The strength of the radar for Iga Nephropathy particular, Vincent we don't anticipate that to be a roadblock for.
Reimbursement for Trustmark.
Great. Thanks, and then maybe a quick follow up on sort of the base commercial business outside of <unk> I guess with.
Potential expansion of the $100 label, how should we think about sort of the trajectory of that base commercial business over time is that a meaningful uptick in the potential opportunity. How are you thinking about that over the next few years. Thanks.
Sure Peter.
Well, we're certainly excited about that.
Tension.
In particular.
Maybe more total patients with CD, except that we will have an opportunity to to reach by educating.
Hum.
The physicians.
We haven't given any guidance what the upside potential is.
We may be in a better position once we see the data all the time.
Great. Thank you.
Thanks, Alex.
Okay.
We will take the next question from the line of Ed Arce with H C. Wainwright.
Your line is now open.
Hi, great. Thanks for taking my questions.
Some have already been asked but I didn't want to follow up on.
A point made earlier and that is.
On the upcoming readout next quarter.
The two year GFS, the Egfr excuse me.
Just wanted to make sure I understood correctly, the primary endpoint here.
Weather was total slope or.
The other slope I think you mentioned started after the first six weeks.
Both of those include integral data points throughout the period and I'm just wondering what those intervals are as well.
Yeah.
Sure Julian would you like to pick up.
Yes, so we'll be looking at.
Hi.
And we have agreements with the regulatory agencies on looking at the chronically ill as well as total slope and Thats an endpoint from the beginning of the study to week 108.
And what are the measurement intervals throughout the period.
Are you asking when patients get labs is that whats.
You are asking I should clarify yes.
Okay. So patients get labs at the beginning and then there was a subsequent lab at I believe it's two four and then eight weeks minutes every three months thereafter.
Okay.
That's helpful.
And just maybe just one last one I know this has been discussed before.
But just wondering as you.
Start this launch.
And have.
Some patients switch from their current therapy onto.
Sorry.
You have a sense for the proportion of patients today.
Visit there are nephrologist on a monthly basis as a routine.
Thank you. Thank you for the question, we certainly have looked into the patient journey and how frequently these patients are visiting Peter would you like to share a bit about work.
Yes.
So the question.
I think.
Especially when you talk about the rapidly progressing patients those patients are being seen by nephrologists at least quarterly, but it's not uncommon to see those spaces, especially on the <unk>.
<unk> please.
This is the heart of your question is like what does it mean from a rent perspective.
Good to realize that for the Rems program those patients don't need to be seen by the nephrology on marketplace and to the left us on a monthly basis emphasis you will see the results, but there is not.
The obligation for those patients to see there.
Nephrologist his remarks, even though it is quite common for quite some patients.
To see dose.
They are nephrologist that awesome.
Got it thank you for clarifying that.
Thanks, Ed.
Okay.
This concludes today's question and answer session I will turn the call back to Naomi Eichenbaum.
Thank you everyone for joining us for our fourth quarter and full year 2022 financial results and corporate update call. We look forward to the exciting year ahead, and providing updates on our progress along the way have a great rest of your day. Thank you for joining us.