Q2 2023 CymaBay Therapeutics Inc Earnings Call
[music].
Good day, ladies and gentlemen, and welcome to see mobile second quarter 2023 financial results and business update conference call. At this time all participants are in a listen only mode. Following the formal remarks, we will open the call for your questions. Please be advised that the.
Call will be recorded at the company's request. It is also being webcast live on the investors section at the Sema being website at Www Dot <unk> Dot com now I would like to turn the call over to Mr. Paul Quinlan General counsel it seem to be Mr. Quinlan. Please proceed.
Thank you operator, and good afternoon, everyone I hope that you've had a chance to review the press release, we issued announcing our second quarter 2023 financial results and business update you can access that release on our website under the investors tab.
Joining me on the call today are Suzhou Shah Chief Executive Officer, Chuck Mcwherter, Chief Scientific officer, and President of R&D.
Stuart Chief commercial officer and Sean.
<unk>.
<unk> Finance officer.
Following our prepared remarks, we will open the call for Q&A.
Before we begin I'd like to remind everyone that statements made during this conference call, including the Q&A session relating to <unk> expected future performance business prospects events or plans, including clinical plans.
To worry approvals funding and repayment schedules.
Anticipated timelines and data release dates cash runway and planning for commercialization are forward looking statements as defined under the private Securities Litigation Reform Act of 1095.
Although the company believes that the expectations reflected in such forward looking statements are based on reasonable assumptions.
The outcomes and results are subject to risks and uncertainties and could differ materially from those forecast due to the impact of many factors.
The company assumes no obligation to update or supplement any forward looking statements, whether as a result of new information future events or otherwise, except as required by applicable law.
Participants are directed to the cautionary statements set forth in today's press release as well as the risk factors set forth in Sema days quarterly and annual reports filed with the SEC for factors that could cause actual results to differ materially from those anticipated in the forward looking statements.
This conference call is the property has seen a day and any recording or rebroadcast is expressly prohibited without the written consent of <unk>.
At this time I'd like to turn the call over to Susan.
Thank you Paul and good afternoon, everyone.
We are constantly advancing towards what is an exciting milestone. This fall when we expect to report topline results from response.
Our global Phase III registration study of <unk> in people with primary biliary cholangitis or PBC.
We anticipate releasing topline results from response by the end of September .
And we will then plan to submit for regulatory approval as soon as feasible.
Our update today includes the announcement of ideal.
An important new clinical study in the development program of sell at El par for PBC and an overview of our pre commercial planning activities for <unk>.
Before we get to these updates let me welcome our new CFO parish shop around to this call.
<unk> joined Us in May and brings over 20 years of experience driving various financial functions and commercial biotech companies.
With a particular focus on setting strategy and building financial planning and accounting operations to prepare companies for commercial drug launch.
We are delighted to have her added during this time of critical broadly for the company as we plan for the completion of our phase III study regulatory filing and commercialization of Philadelphia for patients with PBC.
His operational leadership capabilities as well as his strong strategic finance and commercial experience will be critical as we embark on a transformation to a fully integrated commercial biotech company.
Turning to our progress with <unk>, we continue to execute on what we believe is currently the largest clinical development program in PBC.
Between our phase II studies prior phase III enhance study the ongoing phase III response study and the open label assure study the development program for <unk> is one of the most robust ever conducted in patients with PBC with over 600 participants including over 300.
Currently receiving treatment with <unk> and our ongoing studies.
It is the depth of clinical data that gives us the confidence and sell at El <unk> potential to offer a clear differentiated second line treatment option for patients who are either intolerant or have an inadequate response to arrest the deoxycholic asset the approved first line agent.
At the Easel Congress in Vienna in June there was considerable discussion among PBC thought leaders industry sponsors and patient advocacy groups that centered on revisiting treatment goals for PBC.
We noted a consistent theme in the dialogue to consider adjusting treatment goals to include normalization of Cola static and inflammatory markers and the need to include improving symptom burden.
Earlier today, we announced the initiation of ideal a study that will compare the effects of cell at alpha a normalization of <unk> versus placebo in patients who continue to have persistent elevations of LP above normal, but below 167 times the upper limit of normal.
A level that has been often used as a lower cutoff and clinical trials for PBC.
And several publications. This population has been identified to be at continued risk for disease progression.
However, they do not meet current guidelines for recommending second line treatment and are not typically included in clinical research.
We believe that ideal has the potential to be transformational for this neglected population potentially resetting expectations for second line treatment.
We are optimistic for the potential results and ideal given sell at El <unk> previous rates of alkaline phosphatase normalization and enhance a population that had much higher levels of a L. P. Then will be recruited to ideal.
We are excited that this study is now actively recruiting and while it is too early for us to comment on timelines for enrollment and data Chuck will provide more detail on this study during today's call.
<unk> is the first in the del Mar class, a drugs that targets <unk> delta in the liver.
Study results to date suggest that it has a differentiated profile for efficacy oncall is static markers of disease, including the registration endpoint of primary composite responsive ILP and total bilirubin and on AARP normalization.
Unique among agents approved or in development for PBC. Prior studies have suggested that a key feature of <unk> profile might be improvement in quality of life by reducing <unk> and those patients with clinically significant itch.
If sell it out Mark profile is confirmed in the ongoing pivotal response study and if the safety is consistent with that seen to date, we believe philadelphia or could be an important step forward in patient care.
If in the future we are able to confirm our expectation of positive results and ideal this would be important to advance our aspirations to remake the landscape for treating PBC to far more than those that are treated with second line therapy today.
On the operational front, we continued to make good progress with our medical affairs organizational build including both leaders and field members having years of experience including in PBC.
We have also been successful in assembling key talent for our commercial infrastructure in line with our pre commercial priorities.
Louis will provide more details later in the call.
Before that let me hand, the call over to Chuck who will provide updates on our clinical progress.
Thank you Sue Cheung.
I am pleased to report the progress we made this quarter and our two global phase III studies of sell adult part in patients with PBC.
We are now entering what is the most important stage of our phase III response study.
Our last study visits are imminent.
And we are diligently closing out activities for final database cleaning and locking.
Followed by Unblinded analysis for top line results.
And this is in all of our development activities. We are committed to the principles of quality data integrity and efficiency.
With the team having many members with experience in pivotal studies, we are well positioned to share topline results on our key pre specified endpoints.
End of September .
Followed by timely in depth communication of results at a medical conference and in a publication.
We can intend to complete and submit regulatory applications for approval as soon as feasible.
The depth of the solid Bell part program is further underscored by the long term safety assure study.
Currently active in more than 25 countries and 115 research sites.
It has over 300 patients taking sell at alpine 10 milligrams.
We expect to shore to contribute to both safety and efficacy data sets supporting our regulatory filings.
And there will be a source of important information documenting the long term impact of sum it up our treatment and disease and symptoms in PBC.
We continue to be encouraged by patient retention in both studies.
And are pleased to report that the most recent quarters. The review by the response D. S. M. B directed that as before the study can continue without any changes.
Our confidence in the clinical profile of sell at Alpine stems both from the robust clinical data set we have accumulated from past trials.
As well as our understanding of the underlying Dell par mechanism driving differentiated and clinically important profiles.
Philadelphia part is the first selective <unk> delta agonist or Dell par to regulate critical pathways important in PBC pathology in the liver, including cholestasis and inflammation.
Given that this is our last call before topline results and there may be many who are just now trying to learn more about our program.
I'd like to briefly recap some of the <unk> profile from our prior studies.
And our open label Phase two study.
Patients taking daily oral sell out of our 10 milligrams.
67% achieved the alkaline phosphatase bilirubin composite endpoint at 12 months previously used by regulators for approval.
And the enhance study.
The sell adult part 10 milligram arms saw over 78% achieved this endpoint at three months.
In addition.
Nearly one in three of these patients and enhanced normalized alkaline phosphatase levels. After three months, despite having an average pre treatment a L. P levels of two five times the upper limit of normal.
With respect to the key quality of life result, amongst patients with pre specified baseline moderate to severe itch those taking sell at alpine 10 milligram for three months had significant improvements compared to placebo and their pruritus intensity using a daily electronic diary.
These results give us confidence and sell auto parts clinical profile and also set our expectations on the range of outcomes that we hope to achieve in response.
Perhaps the high point for me on today's call as the opportunity now to talk about ideal.
Study that we have been working on initiating over the past few months.
First let me give you some background for context.
Beginning in 2020.
Publications from the global PBC study group have shown that patients having any elevation of alkaline phosphatase above normal.
Alright at a greater risk for disease progression than those with normal levels of a L. P.
Our early market research suggests that in the U S greater than 20000 patients on U D. C. A may have a persistent a L. P level between one and 1.67 times the upper living a normal.
These patients would typically be managed by treatment with U D. C. A N a wait to fail paradigm in spite of evidence of the risk of their progression of disease.
To make it worse they wouldn't be eligible for clinical studies of new second line agents.
This is where ideal has the potential to lead the way to gather some critical evidence that this population could be.
Benefit from additional treatment with sell at El par.
Given the situation for this overlooked population, we believe that the ideal study is groundbreaking for patients.
Ideal as a phase III randomized placebo controlled study of patients with a diagnosis of P. B C taken.
Taking a stable dose of U D C a unless intolerant.
With a L. P levels between one and 167 times the upper limit of normal.
It is planned to randomize 75 patients two to one daily oral sell it up part 10 milligrams to placebo with <unk>.
Treatment plan for 52 weeks.
Primary endpoint will be a L. P normalization at 52 weeks.
All other eligibility criteria and many secondary and exploratory endpoints.
Similar to prior studies of sell at El par.
Writers will be evaluated using the daily electronic diary.
In a poster we presented at easel in June .
We reported that approximately half of the patients screened in our prior P. D C studies to sell it apart.
Screen fail because of a L. P levels that are between one and 167 times upper limit of normal.
The prevalence of these patients provide us considerable encouragement regarding the feasibility of enrolling in this study.
Before I turn the call over to Louis to discuss our pre commercial preparations for sell at L. Par.
I'll provide a brief update on the progress in our phase Iia proof of pharmacology study for M. B X 29 82.
As a reminder, mdx 2982 at G. P. R 119 agonist discovered and developed by Sema Bay.
It is being investigated for its potential to prevent or minimize hypoglycemia in patients with type one diabetes.
The study is fully funded by the Leona am and Harry Helmsley charitable trusts with Sema Bay, retaining all rights that'd be at 29 82.
In addition to safety and Tolerability.
Primary endpoints or maximal glucagon release, and glucagon area under the curve.
N B X 29, 82 treated patients versus placebo.
The study is now fully enrolled and we expect to share data before the end of the year depend.
Depending on the results from this study will determine the next steps related to the clinical and regulatory path.
With that I will turn it over to Lewis.
Thank you Chapman.
Over the last few months I've continued to emphasize sema based commercial vision driven by an unwavering focus on PBC and its stakeholders utilizing a high touch engagement model that is supported by scientific rigor and innovation.
During the first half of 2023, we have been diligently building the foundation of our commercial infrastructure.
We began by developing a highly specialized distribution model designed to support the patients and their providers throughout their treatment journey.
In parallel we established agencies of record to support sell about par patient and HCP marketing programs as well as kicked off new programs designed to enhance <unk> corporate brand media outreach and of course ongoing partnership with all global PVC Abaca.
C groups.
During the second quarter, we were fortunate to recruit and hire key senior commercial leaders and marketing.
<unk> access and commercial operations, each of whom come with considerable experience and will have in our central role as we accelerate our commercial build and alignment with key corporate milestones.
See what a success in achieving our commercial vision begins with the science of selling they'll par and its potential for resetting the ideal bowls for PBC treatment or.
Our secondary research indicate that less than 40% of UDC a treated patients are able to experience a complete response in other words normalization of a L. P and total bilirubin are.
Our research suggests there is an opportunity to improve biochemical response.
And reduce symptoms for a significant proportion of patients not being treated with second line treatment today.
We're very excited with the initiation of the ideal study and its potential for expanding sell of their parts utility in this target population.
I'll now hand, the call over to Harry to discuss our financial results.
Thank you Louis and good afternoon, everyone.
The second quarter was another productive one for Sema Bay.
As highlighted by everyone. Before me, we made significant progress towards meeting our key objectives for the year related to the development regulatory and pre commercial planning.
In terms of financials, we finished the quarter with a strong balance sheet with cash cash equivalents and investments totaling $213 8 million as of June 32023 in line with the prior update call. We believe that cash and investments on hand are sufficient to fund sema based operating.
Plan through the third quarter of 2024.
We recognized $31 million of collaboration revenue in the second quarter of 2023. Following completion of the initial technology transfer to <unk> associated with the license to develop and commercialize sell adult bar in Japan.
After $34 2 million upfront payment paid Bangkok, and $2 7 million remains deferred and will be recognized upon completion of the company's ongoing clinical data delivery and CMC development performance obligations.
As far our operating expenses research and development expenses for the quarters ended June 32023, and 2022 were $19 5 million and $17 nine.
9 million respectively.
Research and development expense for the quarters ended June 32023 were higher than the corresponding period in 'twenty, two and were primarily driven by higher personnel costs to support our clinical studies and regulatory activities as we continue to progress in the late stage development of cell at our park in.
PBC, we expect our overall research and development expenses to increase in the future.
Turning briefly now to a review of general and administrative expenses. These costs for the quarters ended June 32023, and 2022 were $11 6 million and $5 9 million respectively.
General and administrative expenses for the quarters ended June 32023 were higher than the corresponding period in 2022, and they are primarily driven by initiation of commercial and medical affairs organization build and some spend related to pre commercial planning.
Overall, our net loss for each of the quarters ended March 31, 2023, and 2022, which point 8 million and 27 one.
$1 million or one <unk> and 31 cents per share respectively.
Net loss for the quarter ended June 32023 or slower than the corresponding period in 2022, due primarily to higher collaboration revenue, partially offset by an increase in operating expenses.
Overall, we expect operating expenses to increase in the future as we continue to execute our development and pre commercialization plans for celadon bar in PBC.
Let me hand, the call back to Sunil.
Thank you <unk> I'd like to take this opportunity to thank our team here at Sema Bay for their tireless efforts.
The PBC patient community and their caregivers for their dedication to our work.
And our investigators thought leaders and investors for their support.
It is the result of these partnerships that we have been able to come one step closer in our journey towards our goal of improving the lives of patients with PBC.
We remain laser focused on this objective and look forward to sharing updates related to topline results from response before the end of September .
We're now happy to take questions operator.
Thank you if you would like to register for a question. Please press the one followed by the four on your telephone you wouldn't.
Here are three Tom prompt to acknowledge Jeremy Quest. If your question has been answered and you would like to withdraw please press the one industry.
Our first question going to the line of yes mean that Rainey with Piper Sandler. Please go ahead.
Good afternoon team and thank you tell much further update congrats on ideal two quick question for you. The first one is I know that you guys have spoken about the ideal study them and in many calls before but I think a lot of investors are wondering.
Why is the time ideal now, especially as we are you know a couple of week going into the top line data.
And then the second question is directed to them on the commercial side, which is what percentage of the current pea be seen market would fall under.
Patients that are somewhere between one to 1.67 felt like the ideal population and then one short many question at the end up I mean, it's quite that.
Alright, thanks for the questions Yeah, So I'll just start off.
With respect to the timing of ideal I think important for me to highlight as we have in prior calls our experience in PBC of course dates back to 2015 and with the extensive work that we've conducted through phase two development as well as our prior enhanced study the timing is really predicated on an expectation around <unk>.
Success.
It's also important for me to highlight that it's many months in the making with respect to planning for a meeting with experts conducting market research to be very thoughtful about how we might.
<unk> from additional datasets that could really reset as we describe potential expectations around treatment.
And benefits for our broader treatment patient population in the setting of PBC. So much of the timing I think from our perspective has to do with planning for success and really being able to deliver a data set as quickly as possible as you might imagine. These patients that we described who have not really to date have been evaluated in the.
Second line setting patients that we believe remain at a higher risk of progression.
Our patients living with the disease every day so our attention into this population is one for which we're excited to press forward on now and excited about collecting that data set as quickly as we can to support more knowledge that we may have around these potential benefits for patients with.
With respect to your second question, maybe I'll just start off in and invite Louis to provide some additional context.
We continue to conduct a significant amount of market research as you might imagine as we particularly advanced beyond responds topline data towards regulatory submissions and then all the planning that Louis and his entire team will continue to conduct from our commercial launch readiness perspective.
Early market research that we have to date suggest that all of the patients. If I just look at the U S population.
Our on ECA.
Post at least 12 months of treatment on you'd ECA. It could be a population that is almost a third of those that are actually taking you DCA that could be patients that remain in this bucket between one and 167 times the upper limit of normal Lewis I don't know if you want to talk a little bit about what we're continue.
Going to do to get a better sense of this population.
We continue to evaluate really how these patients are flow through their treatment of UTC.
As I mentioned in my earlier comments about less than 40% of those patients actually experience a complete response. So we tend to segment. These patients out as of course as Suzhou described the 20 thousands that are partial responders.
And then on into those patients that of course above $1 67 times upper limit of normal which are the incomplete responders and of course as we've defined the second line market based on poise criteria.
167 times upper limit of normal that's about 25 to 30000 patients. So we continue to look at this population will continue to understand exactly how those patients really experience not just from a standpoint of liver health, but also of course symptom management through we think that between both.
The complete responders and those that of course are partial responders. There are probably about 15000 patients that continue to experience pruritus. So that's how we're looking at it now, but we'll continue to look at that data.
Thank you Tim and then just in regards to the timing of response I just want to make sure that everyone is clear.
When you're saying the data it's coming by end of September does that mean, it could be any day between now and the last day of September .
Or option do it will come and timber and I'll jump back into the queue and thank you for allowing me to ask my question.
Sorry, yes, yes, the expectation has always been that we would release top line data before the end of Q3.
Importantly, we highlight that we wanted to have appropriate quality and data integrity as we close out final visits follow up visits cleaning and locking the database I think I would simply leave it as having an expectation that the top line results will come sometime in September .
Thank you so much and best of luck. Thank.
Thank you.
Our next question is from Steve <unk> with Raymond James. Please go ahead.
Got it thanks, so much for taking the questions I have two on <unk>.
One is just you published some data so I think David I think a diesel.
On the screen failure rates for your prior clinical studies and it was something like a quarter of screen failures.
A quarter of patients screened I believe in fact actually failed on the basis of having this range of Lp's like sub 200 over 250 patients let's say.
Does that mean like are these patients essentially in the care of your investigators and very easy to go back and identify and enroll the study.
Rapidly or will this be sort of starting from scratch and enrolling.
Steadily.
Despite that dynamic and then the second question is just pruritus in this population.
Do you have any data in sense of if it's similar or less prevalent.
LP levels, then it would be in.
In the population with over $1 67 times upper limit of normal okay. Thank you.
Yes, Thanks, Steve for that question I think you've identified a strategy that of course has occurred to us too.
Go back to investigators who would want to be involved in ideal who've already screened patients and Mei.
May know patients who would potentially qualify so that of course is a lever that we have.
We will pull I would say a couple of comments when you say easy of course clinical research. It always takes attention and it's it's never.
Something that we take we take lightly I do I would add a comment that based upon our experience look there's there's no competing trials for this population right.
Is the first example, where we know where a sponsor to step forward and said we want to study.
Patients with this level of alkaline phosphatase to find out what what might benefit might accrue to them. So I do think we have an opportunity to move forward very expeditiously. In this study, we're not ready to communicate any timelines yet because were basically just off the mark now.
We're pretty pretty excited about the potential and I must say that the feedback from our experts who we consulted when we first <unk>.
<unk> of this idea and then developed a protocol as well as the investigators is extremely enthusiastic so stay tuned for that in terms of pruritus.
So it's a it's a hard question to answer.
From a perspective of pruritus intensity thats used in the study and a clinical research setting because we don't gen.
Generally collect.
With an electronic diary with a 24 hour recall those values, but if you'll look at our poster that we presented it is what you can see as you can look at medical history of pruritus and it was very significant in this population.
Wouldn't want to draw a conclusion about exactly the same one as greater one is less just because of the limitations and the methodology that I mentioned, it's really just a patient saying.
Yes, I've been vexed with itching before but we do think that it's quite common and in fact, if you look in the literature, you'll find that generally speaking there is not a strong collect connection between levels of alkaline phosphatase and pruritus and in fact published work with you DCA, which is a drug that.
For many patients has.
It could affect on disease activity it lowers alpine phosphatase it can affect bilirubin it doesn't affect pruritus, so while pruritus as a consequence of the disease. It doesn't travel in lockstep with the level of disease activity. So this is another interesting ad.
Aspect for us as we examine cell adult par, which at least initially appears to have effects on colas static markers as well as pruritus.
Perfect. Thank you.
Our next question is from Kristen <unk> with Cantor Fitzgerald. Please go ahead.
Hi, everyone. Thanks for taking my question I know in your prepared remarks, he talked about quality of life and symptom burden really being a major issue that physicians are looking to address with new treatments. So given the huge unmet need in addressing pruritus can you talk about what specifically.
You would characterize as a win here in the upcoming readout.
Yes happy to start off in and answer that question Kristen I think important here first to recognize that existing treatment as Chuck mentioned with UDC a the only existing first line treatment. It's never really been shown to reduce pruritus in patients with PBC and so as one element of <unk>.
Quality of life for patients you have got a first line treatment that has yet to demonstrate real benefit on improving quality of life from that perspective.
The only existing second line treatment a vertical like asset in the U S of course has been shown to cause or worsen edge. So when we look at the totality of the evidence that we've generated to date with solid L. Par whether it's from our phase II studies looking at V. A S scores on pruritus or even the scores from the <unk>.
It's scale in PBC 40 questionnaire as well as of course, the placebo controlled benefits. We saw 10 milligram sell Adele par and enhance that reducing an IRS, even the responder rates for patients with three and four points or greater reductions in edge and sell at alpine versus placebo and.
And then marry all of that with the evidence that we shared at easel with respect to IL 31, and an inflammatory cytokines, that's been associated with ICH and seeing those reductions correlate with patient reported reductions in edge, we fundamentally believe that the benefits patients have on pruritus with sell at El <unk>.
Quite real and so we think a bit about the win clearly there is an opportunity to differentiate when you don't cause or worsen niche from existing second line treatment.
But obviously, our aspiration is really suggestive of what we've seen to date with solid out bar, which is to see this improvement.
And so our expectation is we'll continue to see this improvement to the degree that we see statistical significance in that measure in response and the key secondary endpoint of course, it puts us in a much stronger position to go to regulators thinking about opportunities to get sell at El Pas approval potentially for actually treating.
Which in PBC patients as well so we think there's real opportunity based on the profile of Philadelphia that exist today, if thats really confirmed in response to take a new.
A new dialogue to patients really for the first time in a treatment alternative that has an opportunity to improve quality of life.
Thank you and can you talk about what additional hiring plan you in just a day after response.
Well I can say that to date, we've started to build out as we mentioned in the prepared remarks, our medical Affairs organization.
In house as well as folks out in the field I think pose topline data with and by the way. We've also done the same with some of our key commercial hires internally marketing market access commercial operations a host of additional folks internally here now at the company preparing ourselves.
Again for a positive result, and ultimately preparing for both regulatory approval and commercial launch post data Youll see us only continue to step up those specific efforts within medical affairs, and particularly within commercial of course, the field force itself would come later closer to <unk>.
Approval.
From a timeline perspective, but we'll have continued activity here in supportive roles within the company again, all geared towards helping us prepare ourselves for a commercial launch if we're successful in response as well as in regulatory submissions.
Okay. Thank you and all the best hunting into the readout.
Thank you Chris.
Our next question is from Patrick Dolezal with lifestyle capital. Please go ahead.
Hi, Thanks for taking the question.
So a couple more on ideal if I may could you just speak to any potential kind of label expansion and the implications of this study or is this kind of more serious study that might support some marketing efforts.
And then as it relates to success in our primary obviously it kind of ultrafast focused how are you guys thinking about variability there and I'm curious if there are any patients in past studies that were like just above 167 X upper limit of normal that may have helped inform the study design there. Thank you.
Yes, well. Thank you Patrick I appreciate your question.
Ultimately, we would think that the potential for label expansion is a question down the road, but of course, it was very much central to our thinking initially.
Initially we worked very hard to develop the strategy for the study.
We had a very concerted effort internally, where we looked at the known distributions of alkaline phosphatase not only at our screening efforts.
That we've done in clinical studies, but also accessing.
Registry data, where we could look at the distribution. So I think what you're kind of getting at is are there any concerns around imbalances or something thats going to lead you astray, where you might have some some representation of alkaline phosphatase.
Not distributed across the range that we're intending to study and I think we've got very comfortable around the design the.
The availability of prevalence of patients both in screen populations in registries. So that I think we're really set up for success.
With respect to.
The label expansion question, I guess I would just say that.
Our first intent is really to gather the data what's the evidence.
Are we.
Convinced that the effects that we expect to see our a vaccine then of course, we would share those results with the medical community and then we've of course submitted this protocol both to ethics committees and <unk> as well as to the agency, we had very little feedback from them other than just in a very.
Supportive way.
I think right now our focus is on response and making sure that we get the first indication locked down those those conversations the cadence of regulatory interactions as you might imagine is very high at this stage and we would we would address the issues around ideal and label expansion basically at a lag.
Point in time.
The only other thing I'd add Patrick is as you know the label based on response would be an indication for treating patients who are either intolerant or inadequate responders to you DCA and with response, serving as the initial registration study.
For approval and that label the idea around ideal is to perhaps have a support for a broader patient population of course.
Part of that key consideration and I think we're excited to have an opportunity to learn how patients in this category may benefit from Philadelphia.
Definitely makes sense I appreciate the thoughts.
Our next question is from Julian Harrison with BTG. Please go ahead.
Hi, Thank you for taking my questions and really looking forward to the response data next month.
An ideal I'm curious if you have any feedback yet from payers regarding what they would like to see in terms of clinical data for reimbursement and patient between one and 1.67 times the upper limit of normal at the start of second line therapy.
It's a good question Julien certainly work that's actually in front of US we don't yet have input yet from payers, but while we think a bit about creating the body of evidence that would support the potential benefits in the population.
Chuck mentioned, we spent a considerable time thinking about the design of ideal gathering input from thought leaders in the field Hcp's and the like and we think very carefully about how this data set may influence treatment guidelines in the future.
So I think with all of that work in front of us inclusive of getting feedback from payers.
These are things that will continue to provide some updates on into the future.
Okay got it. Thanks, that's helpful and then beyond the ideal for those with incomplete response that you DCA, but have not yet gone onto pursue second line therapy.
Is there a prevailing reason why these patients are not taking additional treatment now and could that change at all in Philadelphia has initially approved supported by response.
That's a good question I think again from some of our early market research, it's very likely a variety of different reasons. When you think about first of all the exists the only existing treatment itself dictates to some degree which patients are willing to go on to second line or our I should even say which patients.
Hcp's believes would be good for the current second line treatment and here again, I think if we're successful with cell Adele par.
On the profile, we've seen to date meaningful response rate on the primary composite endpoint to bring patients below 167 times the upper limit of normal.
A meaningful proportion of patients actually fully normalizing alkaline phosphatase lipid parameters clinical symptom burden using of course <unk>.
As a key element of that improving over time and to date good safety across both non cirrhotic as well as compensated cirrhotic that we've studied to date. When you think about that overall profile. We certainly believe there'll be more patients that are not yet on second line treatment today moving to second line treatment and so.
Excited about having additional treatment alternatives for those patients that have perhaps been hesitant or perhaps haven't been considered for second line as of yet.
Okay, great. Thanks very much.
Our next question is from Jay Olson with Oppenheimer. Please go ahead.
Oh, Hey, congrats on the progress and thank you for taking the questions.
Can you talk about the REIT of normalization, you've seen with Philadelphia or in the enhanced trials for patients with <unk>.
167, the upper limit of normal and how could we potentially extrapolate that normalization rate to a population of patients with LP.
Between one and $1 67.
Well at least I'll highlight enhance here and maybe give some additional commentary Jay. Thank you for the question.
I think and enhances as <unk> seen with the data at three months.
10 milligrams, we saw about 27% of patients normalize ARLP again. These are patients that started above 167 times upper limit of normal as you highlighted the baseline of course and enhance was around 290 units per liter.
Across the enrolled population in each arm.
So.
Obviously striking when you compare that to zero patients out of roughly 55, and placebo that normalize that three months I think a bit difficult for us to extrapolate here for this population of course, the baseline that ultimately becomes enrolled an ideal will be one parameter that has influence but I.
Take you back to data, we've shared and is in our in our published literature around the percent reductions we see in alkaline phosphatase from baseline.
I think largely the guide as we think about the potential to bring patients that are at these lower levels of alpha <unk> fully into the normal range and remember these are patients were enrolling who despite being on <unk> for at least 12 months are at these levels above normal and below 167 times the upper limit of normal.
So with what we've seen with <unk> versus placebo I think we'd expect to continue to see these 45% reduction potentially in this patient population because it is not a measure that's been dependent on baseline ARLP and I think that will ultimately dictate what we see in terms of the data set out of ideal.
Yes, just this is Chuck Jay Thanks for the question, maybe I'll just add.
Just the fact that if you take 167 times upper limit of normal which is in our reference range is right around 196 units per liter.
A 45% reduction that's that's below the upper limit of normal that's actually <unk> nine times, the upper limit of normal not to say that you would of course, you wouldn't expect that to that 45% as an average and the baselines are going to be an average youre going to get some distribution if patients are to drop out of course, they're imputed.
Non responders, but it just kind of set to I guess, it's encouraging to know that at the top end of the range. If you get the average response youre actually normalized.
Okay, great. Thank you so much that's super helpful and I had a couple of follow ups if I could.
Do you know if the patients who are currently between one and 167 times upper limit of normal are receiving off label treatment with OCA based on your market research and if so what sort of response would be.
Yes, that's another good question Jay we don't really believe these patients are in fact off label therapy, particularly in the U S is not what we believe a very significant proportion of patients.
And so I think fundamentally these are patients that are just lepton you'd ECA.
As the best alternative and wherever their ARLP lands. They are maintained at those levels effectively. So this is what's exciting about an opportunity perhaps to to demonstrate some additional benefit for this patient population.
Okay, great, Thanks, and if I could sneak in one more question.
Can you just talk about what percent of patients in response have rolled over into the assured study.
Yeah, we haven't provided specific numbers, there Jay but historically, we've seen across our prior studies when we've had long term extensions ongoing.
A significant proportion of patients actually roll into the long term extension over 90% historically, so as we've mentioned assure now has over 300 patients.
As many of which came from prior studies, but of course, many of which now as responses nearing completion have in fact rolo rolled over into response. So it's a it's a high number.
Based on the patient experience from our from our clinical studies to date.
Great. Thank you so much I appreciate you taking all the questions.
Yes.
Our next question is from Andy <unk> with William Blair. Please go ahead.
Thanks for taking our question so just.
Couple of quick ones.
Or are the ideal study.
Any plans regarding longer term follow up or basically these patients will eventually be rolled over to assure as well.
Yes. So currently we haven't put in place an opportunity for those patients to rollover into assure but we're at the beginning of the study I guess, we wouldn't necessarily rolled out out another option would be to open up an extension of ideal and then depending on things how.
Play out.
Potentially even transitioning to commercial so we'll have to see we're just at the start now it's a good question, but I just don't have an answer for you yet.
Got it that's fair.
And since we are on the theme of expansion opportunities.
Just curious about your thoughts on potentially combination therapies going forward, maybe perhaps like a AAA with five rates happy.
Happy to hear your thoughts there.
Yeah.
Yeah, I think there are a number of pads forward as we think about broader treatment for the treatment landscape in PVC.
Of course, there will be some patients even after you'd ECA and if we're successful sell Adele par se as a second line agent that may require a third agent who have all ultimately highly elevated out fast.
So we haven't yet committed Andy to any specific studies or strategies, there, but I can tell you. We've got a team that continues to think thoughtfully about additional lifecycle management as we think about success hopefully post response.
Got it got it and I just want to make sure. So for ideal. The requirement is basically patients would have to be argued ECA for 12 months right. So it can be six months three months has to be 12 months.
That's right. We are following the standard practice, we want to enroll a population that couldnt be criticized as being something thats not.
Or not.
More traditionally a second a second line.
Treatment I would mention though that of course, they can be intolerant to <unk>. So.
They have levels of alkaline phosphatase between one and $1 67, but simply can't take you DCA they've tried it before and not able to tolerate it they would also be eligible.
Got it that's very helpful.
Thank you so much thank.
Thank you.
Our next question is from Ed Arce with H C. Wainwright and company. Please go ahead.
Great. Thanks for taking my questions.
Congrats on continued progress with the study.
Regarding <unk> I know you've mentioned this on this call already.
Obviously label expansion.
As.
Clearly our goal there are women.
To ask you though.
That would be.
A reason to also consider.
Further data expansion on label with your quality of life measures.
Regarding pure itis fatigue, two two of which I know you've.
Collected and generated data on your trials.
<unk>.
Yes, and then I have a follow up.
Yeah, and I, certainly say that is absolutely a focus of ours as well as we continue to generate data on pruritus as well as some data that we hope to gather in response, particularly from the PBC 40 questionnaire around fatigue. These will continue to be areas that we invest as we better understand cell at El <unk>.
Thanks on both of these symptoms of disease and quality of life overall.
Sure.
Yes.
Great.
With regard to pruritus.
<unk>.
Wanted to ask you you had a sense from the agency.
And including additional data how important.
Would it be to have.
The mechanistic rationale.
You have now at least.
Initially with IL 31, and having some of that.
Rationale as part of underlying this in supporting the inclusion of some of that data on a on a future label.
Well. Thank you for mentioning that at of course, where we're pretty interested in very.
Tensely thinking about IL 31, and the mechanism, which is the mechanism of Cola static practices.
Really not been understood for decades.
I wouldn't want to speak for regulators I don't know how they think about it are going to think about it hopefully they take a scientific perspective I think that.
Of course, pruritus, not only for PBC, but for many different diseases is subjective.
The thing that you can you can measure only the patient can tell you about a symptom.
Now moving to something that could potentially be considered.
A biomarker is really intriguing I think that would be something if I were a patient would be.
Feel very validated.
Now I have something that I can lineup with <unk>.
We're experiencing with what's something that can can be can be measured.
So starting point and also just to know how well people respond pruritus is something that fluctuates.
Quite a bit having something you can measure I think is quite interesting at.
At the end of the day, I really kind of coming to your question whats the FDA kind of look at it I think they're going to start with the patient reported outcome have we used appropriate methodology.
The data robust do we have data that supports a sensitivity analysis that confirm not only the key measure of pruritus that we negotiated with them, but also.
Suggest that there is additional independent ways to measure it I think they're going to focus on that first because its a patient reported outcome, but having something else. It's biochemically our laboratory related I think.
Well at least let the medical community have some increased confidence.
What regulators to we'll just have to wait and see.
Right great.
One last one if I could.
For her ish.
I think you had mentioned in your prepared remarks.
And expectation for overall Opex.
To increase.
I realize all of this is related to the.
Commercial build out and launch preparations, but is there any sense.
Qualitatively or just subjectively too.
Describe the.
Three of increase.
This year and into next year.
Thanks.
And the only thing I would add I think Suzhou had talked about I mean are our infrastructure were building both on the medical side as well as in the commercial side is for bringing on our MSR and then the commercial will accelerate.
Added some.
Keith commercial leaders now, which will and then we will bring in more as on the other side of beta.
And I think the the main I would say the lift will be on this when we bring on the field teams, which will be mostly next year closer to approval. So I think the goal is to make sure. We have the best possible launch and to support and to have the resources required to support that.
And that I am not in a position to give any quantitative specific guidance on what the level of that spend would be but we're making sure having that infrastructure that's needed to support launch.
I think what's helpful. There Ed as you think about the runway guidance of having cash that takes us at least to the end of Q3 next year that can help you with some estimates.
Great. Thank you.
Our next question is from Thomas Smith with Leerink Partners. Please go ahead.
Yeah.
Hey, guys. Good afternoon, thanks for taking the questions and let me add my congrats on all the progress just a <unk>.
Follow up on pruritus.
I guess based on what we've seen from the Ela figure nor top line it doesn't seem like it.
And we'll be able to claim an explicit benefit there I'm just wondering within all of your recent market research.
Whether you've been able to quantify clinician prescribing preference for an agent that is explicitly labeled would that benefit versus.
Versus an agent that has data, suggesting a trend toward improvement, but isn't explicitly labeled like all things being equal have you been able to quantify the incremental benefit of having the pruritus claim on the label.
We don't have a very specific.
Specific.
Increased I can give you, but I can tell you qualitatively. There is no question there is significant.
Impact that we see in the overall expectations for utilization.
Just on on pruritus, and having the claim I think that.
Couple that with really the fact that patients really tell us so.
So think lead how their expectations around symptom burden.
Really aren't being addressed by the providers and of course providers just have not had the tools to address those and I think that as we think about a new paradigm for treatment not only will you have certainly providers interested in wanting to utilize sell a del <unk> in that setting, but theyre going to be patients coming in and saying really.
They want to be able to address this issue.
<unk> been plagued with throughout the course of the disease. So I think what we see qualitatively is extremely strong preference for an agent that provides that benefit.
Okay.
Got it that's helpful and then I was just.
Wondering if you could elaborate a little bit on some of the.
Sort of pre NDA preparation activities things that you can kind of undertake now to try to help prepare for the submission and maybe try to close the gap between the time from topline data to NDA submission.
That's a great question Thomas you can imagine that anybody in our industry and our our situation who wants to be successful is doing exactly what you are alluding to.
Yes, there are a lot of things that are complete.
And the non clinical space, we've made a lot of progress in manufacturing.
We have prior clinical studies that are completed and closed out.
We have ongoing studies that are approaching completion for which we have a lot of information we can assemble into all the documentation that has to be assembled.
And QC made.
Made consistent.
All of those efforts are in place we rebuilt our teams really around this as being the most important activity in the company.
Have supported that with additional expertise consultants and the like who have experience in this space that can set us up.
To succeed so I think what youre getting at is that you do as much of the work you're prepared as much as you can.
In advance so that you are ready to.
Could drop the data and so to speak and I think thats really what everyone does and this and this.
Situation.
Got it that's helpful. Thanks again for taking the question.
Our next question is from <unk> <unk> with B Riley Securities. Please go ahead.
Walking and team thanks for taking our questions and congrats on the progress in.
<unk> joined the team here, so maybe just on that run rate comment.
Beyond the ideal what additional trials are sort of baked in the runway guidance.
It's about in the past about ecosystem population outcomes, obviously onshore it is top of mind in any crossover study to solidify brightest label and maybe for Chuck you guys do get very broad spectrum of liver biochemistry going down any any any of their trials and field work even.
In ideal that looks at the complete biochemical response as an endpoint, which obviously is also.
It is being dumped about and that <unk> in that.
The evil proved that you talked about.
To hear your thoughts on that.
A quick follow up.
Michael Let me first start with the question on on the R&D clinical trial.
Expenses right I think you listed some of the key ones. There. We spoke about are sure of course, which is why we haven't drilled over 300 patients thats. The long term study that's actually currently.
And besides that ideal as we talk about this as something that will expand as we recruit.
<unk>.
Patients in this study and then the other one is the outcome study that we will have so we will be initiating and this is part of our <unk>.
Filing so we need to have that activated and enrolling so you will see that ramp up. So those are the three main ones that I would say from a clinical trial.
And our perspective that we would hit it from an R&D spend lengths and those are the main falls out there.
Chuck I don't know if you want to ask the other part of the flush yeah. So thanks. Thanks for the question.
As you've seen the reason presentations, both from us as well as from others.
Normalization biochemical parameters is very appealing.
The total normalization or if you wanted to call it biochemical remission.
Of course, as something Thats talked about but it's not actually receive the same level of validation and its certainly not true that the.
Regulators are thereby by any means.
In terms of whether the medical community will move there I think that the concept is appealing qualitatively, but I don't think quantitatively.
It's yet it's yet happened and the issue really relates without getting.
Too far into the into the weeds.
<unk> parameters to what extent are they true independent covariance or how often do they just travel together or you're just measuring some of the same thing we know from the work from the global PBC study group from the UK PBC group from some of the work coming out of the.
National registry as well as the Dutch registry.
But the key ones that theres really not much debate about our Alco and phosphatase bilirubin is especially a powerful one and we are beginning to understand that liver injury.
Elevated transaminase as in particular Allt reflects ongoing inflammation and has been linked to fibrosis.
In other liver diseases like Nash, but also in PBC using histological evidence with long term follow up.
So those three we believe have the strongest level of evidence.
They would get the most.
Near term.
Embraced so I think from the medical community.
Clearly ARLP and bilirubin or already.
To a degree at least accepted by regulators, although one still needs to look at outcome studies and we believe the datasets.
We're going to produce or going to suggest that <unk> is also an important parameter.
Beyond biochemical normalization I think I would also mention that a lot of attention is moving towards non.
Non invasive measures like liver stiffness using fibers Grand our transient Elastography I think that has a lot of merit some of the work coming out of Chris.
Christophe copper show as the lead.
Is really suggesting PVC like other diseases. This is going to be an important.
Measure in terms of serial long term follow up for patients potentially in clinical research and we by the way include those that are long term studies.
But importantly, I think this is going to be used is being used to actually I should say in medical practice. It is being used to follow patients.
Many clinicians who will use it to make decisions and judgments around how patients disease progressing especially towards cirrhosis.
Okay.
Okay.
Very helpful. I appreciate that comprehensive color there and then just on response.
As you know out there.
In another study.
Without.
Questions are asked obviously about we have not seen the full data, but if you could comment on your expectation for.
Discontinuation rate and also on the <unk> score would perceive or response youre expecting there.
And thanks again for taking my questions.
Thank you Mike.
With respect to discontinuation rates I think historically, we've seen rates that have been less than 10%. So that would continue to be our expectation with response again, we anchor on very significant patient numbers from our prior experienced north of 100 patients in our one year phase III study and obviously randomized 265 patients into it.
Enhance even though that study had been terminated early.
So I think we continue to have the expectation that we see very similar.
Expectations around discontinuation.
With respect to NR as again I think all we have with respect to placebo is the data in enhance itself. So with patients that came into the study with an NRC for greater where the baseline and placebo as well as the treatment arms was six point to we saw this one five point drop in <unk> in the placebo arm.
That's today are only expectation and the best data set we have obviously here, we will have more significant number of patients with <unk>.
You'd expect to see roughly 30% of our patients coming into response with at least in <unk> or greater as well. So that's our historical experience is really the only data point that we have to date.
Thank you. So I appreciate you, taking our questions and all the best.
Thank you.
Our next question is a follow up from Jay Olson with Oppenheimer. Please go ahead. Please go ahead.
Hey, thanks for taking the follow ups.
With the increased emphasis on treating PVC early and aggressively it seems like the ideal study is one step closer to first line treatment. So I was wondering if you could please share your latest thoughts from.
The pursuit of a first line indication for <unk> in PBC. Thank you.
Thanks, Jay I think.
We do kind of hold to the sentiment too.
Treat the normal treat earlier treat the symptoms, whether we would actually be frontline I think is a little bit further away from us. Our current focus is really trying to get the second line indication and getting data in this and this.
Additional population.
Going for a frontline therapy has very specific implications for how one would conduct the trial.
Good.
Potentially need to be a comparator trial it might need to be an outcome trial, because <unk> was approved based upon outcome. So theres a lot of different implications I think solid el par can be enormously beneficial patient to patients if we confirm the profile in response.
I think it has a really bright future in terms of its positioning its availability, but I wouldn't want to set the expectation at least right now that were that it's a it's an easy reach to move to frontline therapy.
Okay, great. Thank you so much for taking the follow up.
Thank you.
And Mr. <unk>, we have no.
Further questions at this time I'll turn the call back to you may continue with your presentation or closing remarks.
Thank you operator ill close today with just a few thoughts first on ideal as we've discussed today work on the design and merits of this important study started by our teams that seem to be many months ago and it included gathering input from market research thought leaders and patient advocacy groups around the world.
We're excited as we've discussed to bring this novel study to many patients with PBC, who have been neglected for new treatment alternatives in many ways to date, we look forward to the opportunity to learn from data. We collect an ideal that we believe may have the potential to reset treatment expectations for a broader patient population that may have.
An opportunity to benefit from sell at Alpine if we're successful.
Over the coming weeks. Our teams are intensely focused on final visits in response as well as cleaning and locking the database.
Continuing rolling eligible patients into assure and of course conduct across many other clinical and regulatory preparatory activities.
Work across all functions in the company has only been accelerating and we're proud about the progress we're making on many fronts.
Finally, we're excited about being back in front of you again before the end of September with topline results from response.
We hope this study can be a significant event for all that have been part of our journey not the least of which are the patients that may benefit from our work.
We hope this may open up a new chapter in the treatment of patients with PBC and we look forward to talking to you again soon thank you.
And that does conclude the conference call for today, we thank you all for your participation and kindly ask that you. Please disconnect your lines have a great day everyone.
Okay.
Uh huh.
Okay.