Q2 2022 Cymabay Therapeutics Inc Earnings Call
[music].
Good day, ladies and gentlemen, and welcome to the <unk> second quarter 2022 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 <unk> website at.
Www Dot Sema Bay Dot com.
Now I would like to turn the call over to Mr. Paul Quinlan General Counsel at Sema Bay. Mr. Quinlan. Please proceed thank.
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 2022 financial results and business update.
You can access that release on our website under the investors tab.
Joining me on the call today are <unk> Shah Chief Executive Officer, Chuck Mcwherter, Chief Scientific Officer, Dennis Kim Chief Medical Officer, Lewis Stewart, Chief Commercial Officer, and Dan Marino VP finance.
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 regulatory approval funding and repayment schedule.
<unk> anticipated timeline and data release dates.
Cash runway and planning for commercialization are forward looking statements as defined under the private Securities Litigation Reform Act of $19 95.
Although the company believes that the expectations reflected in such forward looking statements are based on reasonable assumptions.
Actual 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 based 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 senior debt.
At this time I would like to turn the call over to <unk>.
Thank you Paul good afternoon, and thank you for joining us today.
I'm excited to start our call today, highlighting the achievement of a significant milestone in the development of <unk> for patients with the rare autoimmune liver disease primary biliary cholangitis or PBC.
Last week, we announced the completion of enrollment in response, our global Phase III registration study evaluating <unk> in PBC patients, who have had an inadequate response to or are intolerant to first line treatment first to deactivate look at that.
As a result of the tireless efforts of our team here at Sema Bay.
The commitment of our patients and their family members.
The expertise of our investigators and their staff.
And the support of our investors, we have been able to bring cell Adele par a step closer to our goal of improving the lives of patients with PBC.
We believe our development program for sell at El Par is one of the most robust ever conducted in patients with PBC.
With over 600 participants.
Including over 325 currently receiving treatment in our ongoing studies.
We have explored a broad range of doses between two and 200 milligrams and have studied a wide spectrum of patients, including non cirrhotic and compensated cirrhotic with and without portal hypertension.
Our current experience includes patients who have been on treatment for between three months and up to three years.
Today, I'll ask our Chief Medical Officer, Dr. Dennis Kim to provide an overview of our progress in response as.
As well as across the entire TBC development program.
Over the years, a key element of our development program has been to publish and present our findings at major medical meetings.
Since the beginning development in PBC in 2015.
We have consistently shared data with the medical community and today, our Chief Scientific officer, Dr. Chuck Mcwherter.
We will review some of our most recent data presented at the international liver Congress sponsored by Easel. This past June .
Finally, as we look forward to completing response and reporting top line results from the trial in the third quarter of 2023, we will continue our pre commercial work to identify strategies that maximize the impact they'll have dealt part can have in PBC.
Our Chief Commercial Officer, Lewis Stewart, who will briefly discuss the work that is ongoing.
And that will be expanded on during a virtual investor event, we are planning to hold in September .
Before taking questions, we will wrap up our paired remarks with our VP of finance, Dan Marino reviewing our financials for the past quarter.
Let me first turn the call over to Dennis.
Thanks, Joe.
It's my privilege to discuss the progress we have made in our phase III development program for <unk> in PBC.
The completion of patient enrollment and response is an important milestone that enables us to set timelines and plan with more granularity for completion of full study conduct data analysis availability of high level of efficacy and safety results and transition to putting together a high quality NDA for potential Martin.
Approval of sell adult par as a novel treatment option for patients living with PBC.
On a relative study enrollment completion, we executed an extensive screening effort at more than 150 active sites and more than 20 countries.
Ultimately, we concluded enrollment with a total of 193 patients randomized.
Patient recruitment and enrollment is always one of the most challenging operational aspects of any clinical trial, but the response study had some additional challenges related to the worldwide pandemic, which started several months prior to initiating response.
Covid related challenges such as workplace shutdown the version of clinical and hospital resources to address Covid infection.
Labor shortages and some patients reticent to participate in our clinical trials among other COVID-19 related factors required us to go further.
Deeper and get creative with patient recruitment strategy.
Other similar studies being sponsored by our competitors targeting a comparable PBC patient profile. We're also being conducted in parallel with the response and the geopolitical strains in Russia, and Ukraine pose additional hurdles to overcome.
To meet these challenges we expanded our footprint with respect to the number of study sites countries and patient recruitment partners.
We sought to build new relationship with high potential investigators in regions of the World. We had not previously conducted trials in.
An intensified focus on engaging the preexisting relationships and study sites, we knew had potential to perform well.
Our rich experience in working previously across various TBC clinical studies with menu of the famed PBC experts principal investigators Allied health professionals and patient advocacy groups served us well and being able to leverage these relationships to meet the challenges.
Indeed, our Suzhou mentioned, our solid up our clinical program represents the most robust and rigorous dataset for drug candidate in development in PBC to date.
We have gathered clinical data across more than 600 patients with PBC through our phase II and phase III studies with greater than 100 patients and greater than 50 patients haven't had at least one year and two year of sabadell part treatment experienced respectively.
In our ongoing open label extension study assure there are currently more than 150 patients being dosed everyday with all adult part.
So the 193 patients randomized in the response study will be our flagship dataset supported by the consistent efficacy and safety results, we observed from our prior trials.
This gives us additional confidence in being able to deliver life changing therapeutic option for those living with PBC.
Through these data collection and experiences working with various stakeholders in the field of PVC.
We're able to glean important and encouraging information and sentiments from our partners.
The ongoing assure study is a significant differentiating feature of our program.
All patients are receiving open label sell bell par on a daily basis, which will add significant amounts of long term efficacy data for biochemical response and pruritus. In addition to creating large their safety dataset.
The data safety monitoring board for response has allowed us to continue without any changes.
Feedback from our investigators on their clinical experience in these studies have been overwhelmingly positive.
Many of these investigators were also involved in our prior studies, including our first phase III study enhance.
Which showed encouraging efficacy and safety results at three and six months.
As a reminder, 10 milligrams of daily Sabadell par treatment and our prior open label Phase II and long term extension study demonstrated consistent sustained and progressive improvements in alkaline phosphatase and the range of approximately 50% reduction after two years of treatment with 79% of patients achieving the <unk>.
Posit endpoint of all cost less than 167 times upper limit of normal.
Greater than equal to 15% reduction in our cost and total bilirubin.
Less than equal to upper limit of normal range.
We also previously reported the progressive improvements in liver transaminase, and an LDL cholesterol over a two year period.
Similarly in enhance 10 milligrams and sell ballparks daily over three months resulted in 78% of patients achieving the primary composite endpoint and more than 25% of patients achieving normalization of alkaline phosphatase from main baseline approximately 290 units per liter.
These biochemical results were okay.
By an improvement in measures of pruritus and important and meaningful symptom of PBC, many patients experience and are hampered by everyday.
Importantly, sell bell par appeared to be safe and well tolerated across the prior segment.
With the pension now focus on our current settings, we anticipate sharing top line data for response in Q3 of 2023.
I'll now hand, the call over to Chuck to share highlights of some of the most recent presentations we made at equal in June .
Jacques.
Thank you Dennis.
We believe that our science is not complete until it's been communicated to the scientific and medical community and ultimately then published in peer reviewed journals.
It was at the liver meeting in 2016 that we presented the results of our first study of Sel at El <unk> in patients with PBC.
And this was followed soon after by their publication in the Lancet Gastroenterology in herpetology, one of the premier journals for liver disease.
Since 2016, we presented research on solid El Pas at every Aaas L D and easily meeting with 33 presentations made to date six of which have been selected for late breaking presentations.
Nearly a third having been oral presentations.
This year, we published the results of the 52 week Phase II study of Sel at El <unk> in PBC in the journal of Herpetology, one of the foremost journals in the therapeutic area.
A secondary analysis.
Reporting improvements in pruritus sleep and fatigue was published in liver International Another journal known for publishing results at the forefront of herpetology.
This past June we continued our commitment to sharing results with three presentations at the easel sponsored international liver Congress in London.
The first presentation was a poster describing research led by purpose or Bettina Hansen.
The leader of the Global PBC study group the group best known for proposing blood tests for Alpine phosphatase and bilirubin levels that are used at surrogates by FDA and EMA as endpoints for approval in PBC.
The poster titled Celadon, <unk> treatment of patients with primary biliary cholangitis for two years improves the globe PVC score and Purdue predicts improved transplant free survival, Utah.
We utilized a validated risk assessment tool called the globe score.
It examine treatment response to sell adult par over a two year time period, and 50 patients with PBC.
The patients were selected based on having an incomplete response or intolerance to frontline therapy with U D C. A.
The main result was at the addition of sell at El <unk>.
Led to a predicted reduce risk for liver transplantation or death with a hazard ratio of <unk> 66, compared to no prior treatment with Philadelphia.
The improvement in globe score and predicted survival did not depend on a patient's age.
However, and analysis of subpopulations of higher risk patients by globe score revealed that patients while of all ages improved the.
The younger patients at high risk tended to have greater improvements.
This suggested the potential for greater impact by treating earlier in disease with sell at El par.
In an oral presentation by our collaborator Professor burner Schnabel Professor of Medicine at the University of California, San Diego. He described an elegant set of studies, establishing that sell Adele part.
Through <unk> delta to suppress bile acid synthesis by Upregulation of FGF 21 in hepatocytes.
This explains the ability of sell it out part to suppress toxic bile acid that accumulate in the liver because of cholestasis.
Importantly, this research establish it that suppression of bile acid synthesis is via an entirely different pathway than that of FX <unk> agonist.
Such as El caliber.
Which is the only second line treatment for PBC approved today.
FGF 19, released by intestinal cells must then travel to deliver to assess its effects on bile acid suppression.
The involvement of FGF 21 may be one of several reasons why the <unk> mechanism.
To have the ability to produce favorable biochemical responses associated with improvement in cholestasis.
The last presentation with a poster from the <unk> research team.
<unk> and the effect of <unk> on fibrosis, and mouse livers subsequent to enter it caused by repeated low dose treatment with carbon tetrachloride.
Our approach was to allow fibrosis to become established for five weeks before initiating treatment for three weeks with cell Adele par or vehicle.
However, unlike some other fibrosis models, we continue to administer the carbon tetrachloride installed throughout the subsequent three week treatment period.
Sell Adele par unlike comparator FX, our ore THR beta agonist was able to reduce fibrosis in the face of continued injury.
Molecular analysis using RNA seek methods was able to establish that sell Adele part treatment changes the signature of genes associated with injury and fibrosis.
This is the third animal model in which we have seen that sell at El par was able to reduce levels of established fibrosis and we believe that this is consistent with other parts of the effects on fibrosis that were observed in patients with Nash.
We continue to utilize cutting edge methods to examine the translation of effects of sell it up on gene transcription to understand its pharmacology and patients.
As you can appreciate we are committed to sharing results of our clinical and mechanistic research and we expect to participate in the <unk> meeting this fall and other major medical meetings going forward.
As we advanced cell at El par through late stages of development. We are also committed to understanding strategies to maximize the number of patients that may benefit from treatment.
I hand, the call now to our Chief commercial officer to Stewart to discuss our early pre commercial plans.
Louis.
Thank you Chuck.
With our clinical team focused on response or lean commercial team worked diligently throughout last year to conduct a global PVC market assessment.
With a specific focus on the U S, Canada, Europe , Japan and China.
Throughout our primary research we were gratified by the reception from health care providers, who reviewed the sell of Dell par target product profile.
The strong preference for solid Revpar as a next generation PBC treatment has been consistent across all targeted global geographies.
It is clear from our market research and expert advisers.
There remains significant unmet needs for enhanced biochemical response and symptom improvement of PVC.
Beginning of 2022, our focus turned to several U S based pre commercial initiatives designed to inform our go to market strategy.
We began by mapping out the estimated 25% to 30000 patients in the U S that we believe make up the second line U S market.
Our analysis demonstrates an immediate opportunity in non cirrhotic patients that have an incomplete response to UTC.
<unk> or have discontinued treatment with a better coal to gas at which make up nearly 60% of the second line target population.
In addition.
We estimate there are up to another 15000 cirrhotic patients on first line treatment.
Whereby over half experienced a partial to incomplete response to <unk>.
And could be a distinct population for sale of Dell par second line therapy, particularly given the black box warnings for a better kovac asset in this population.
Another important consideration across the spectrum of both UTC, a complete and incomplete responders.
Are the over 15000 patients who experienced moderate to severe pruritus and may look to sell a dell par for symptom improvement.
Overall, our segmentation analysis shows <unk> product profile could be a preferred choice for the great majority of these distinct patient segments.
In the second quarter, we conducted patient centered research examining their journey with PBC.
And we're encouraged by both patients and the families active engagement in their overall care.
Furthermore, we are excited about the overall knowledge of PBC patients and their willingness to learn about new potential treatments.
As expected they.
We're very descriptive of the symptoms they endure providing distinct details regarding the severe pruritus fatigue annual brain fall that is such a significant part of their everyday lives.
Along with their healthcare provider they consistently monitor key biochemical markers and are constantly anxious about their overall liver health.
At Sema Bay, we believe that we can provide patient and caregiver education.
Add to the conversation around quality of life issues.
And become a trusted source of information alongside the great work of advocacy groups like the PVC PVC.
PVC Foundation Canadian TBC group and others, we are engaged with globally.
This past quarter. We also conducted a market access landscape evaluation, along with primary market research with payers to identify both opportunities and barriers across the spectrum of <unk>.
Health plans examining both commercial and government coverage.
We will utilize these initial findings to inform <unk> value proposition and overall payer and patient support services strategy.
Lastly, <unk> briefly highlighted we're planning to hold a virtual investor day on September 22nd where.
While we will be providing a more detailed review of the global market opportunity for <unk> included in this agenda will be a clinical review by Dr. Chris Cowardly, one of the foremost global experts on the treatment of PBC.
We're excited to share more with you on the commercial planning work, we continue to conduct and we will keep you informed of details about the event in the coming weeks.
I'd like to now turn the call over to Dan <unk>, Vice President of Finance for a review of our financials in the second quarter.
Dan.
Thank you Louis.
As others on the team have highlighted during the second quarter, we continued to make additional enrollment progress and our assure study and last week, we announced completion of enrollment of 193 patients and the response study thus achieving a key milestone in our PBC development plan.
We also continued to advance other required clinical activities associated with our response for sure and other NDA, enabling clinical studies, which are necessary to complete our late stage development of Philadelphia and PVC.
And finally, we made progress in manufacturing development as well as in medical Affairs, and commercial where we continued efforts to plan for a potential future launch of <unk> in PBC.
Turning to a brief review of our second quarter financial position and operating results, our cash cash equivalents and investments totaled $178 million.
As of June 32022.
We believe this cash on hand is sufficient to fund our current operating plan through 2023.
Our net loss for the quarters ended June 32022, and 2021 was $27 1 million and $23 2 million or <unk> 31, and.
<unk> 34 per share respectively.
Net loss for the six months ended June 32022, and 2021 was $54 9 million and $40 8 million.
<unk> 60, <unk> 59 per share respectively.
Net loss was higher in the quarter and six months ended June 32022, compared to the corresponding periods in 2021, largely due to an increase in clinical trial operating expenses associated with the ongoing late stage development of cell Adele part NPV.
As well as an increase in non operating interest expense accretion related to the adding worth development financing arrangements.
In particular, our operating cost increases were primarily driven by an expansion of our clinical site activation and patient enrollment and other clinical trial activities associated with response to assure our two active global late stage clinical trials in PBC and higher employee compensation associated with the <unk>.
<unk> of additional personnel to support the overall PVC development program.
We expect our operating expenses to increase in the future as we continue to execute on our clinical development manufacturing and commercial readiness plans for PVC.
Let me now hand, the call back to Sudhakar.
Thank you Dan.
In addition to our primary focus with <unk> and PBC.
The phase Iia proof of Pharmacology study of <unk> 2982 continued to enroll patients in the second quarter.
Challenges related to the COVID-19 pandemic continue to impact the pace of enrollment in this study but.
But we believe our partners who are fully funding and conducting this trial can drive towards completing enrollment by the end of this year.
As a reminder, <unk> 2982 is a GP or 119 agonists discovered and developed by <unk>.
And although this trial is being fully funded by the Leona EM and Harry B Helmsley charitable Trust.
We retain all rights to <unk> thousand 982.
The product concept being investigated for Mdx 2982 in the current study is as an agent to potentially prevent or minimize hypoglycemia in patients with type one diabetes.
In addition to safety and Tolerability. The primary goal of the study is to evaluate the levels of counter regulatory glucagon release under conditions of low blood sugar.
We look forward to providing more updates on the progress of this study in the coming months.
It's been another eventful quarter at Sema base, and which we are proud of accomplishing key milestones and more importantly excited about the news flow that lies ahead.
We believe the potential for solid Elkhart to meaningfully improve the lives of patients with PBC represents one of the most compelling and derisked late stage opportunities in our industry.
Our goal has always been to put sell Adele par in the hands of as many patients that may benefit globally should we be successful at completing the development program and registering solid L bar.
As part of this we continue to evaluate alternatives to partner with parties in geographies outside the U S.
Where there would be an opportunity to significantly create additional value.
<unk> remains one of the only late stage opportunities in this area that remains fully unencumbered.
With a strong balance sheet high quality investors experienced internal team and partnerships with the best experts in PVC around the world.
We couldnt be in a better position to continue creating value for all of our stakeholders, including patients who were focused on every day.
We're now happy to take questions operator.
Thank you ladies and gentlemen at this time, we'll be conducting a question and answer session.
If you'd like to ask a question you May press star one on your telephone keypad.
A confirmation tone will indicate your line is in the question.
You May press Star two if you would like to remove your question from the Q.
Participants equipment, it may be necessary to pick up your handset before pressing the star.
Our first question comes from the line of yes, yes.
Romney with Piper Sandler. Please proceed with your question.
Hi team congratulations again on the enrollment completion, a number of questions maybe the first question.
Are you able to shed some light whether you have had a chance to look at the baseline demographics treatment response.
Maybe help us understand how much it's aligned with the enhanced study that's question one.
Question, two if maybe you're right a reminder, on the powering assumption out their response study.
And then the third question asked.
Have you started to interact with the FDA in regards to what a post marketing requirement may look like I know, we have seen from competitor trials Fad.
Let's see bow controlled studies and post marketing might not be feasible.
And thank you so much for taking our questions.
Thank you I appreciate the question.
I'll start off and perhaps ask the team to elaborate on some of these points I think first of all with respect to response.
We've talked at length in the past about how this is largely I'd like to say, a rinse and repeat.
What we.
Fully enrolled and enhanced and executed in the enhanced prior phase III study, we're really looking at the same patient population. The same optimal 10 milligram dose of cell Adele par and the same primary end same two key secondary endpoints of course on a blinded fashion, we have the ability to see some of the high level of baseline demographic.
By simply tell you, yes, I mean, we wouldn't expect to see anything really all that different from what we've seen in over 100 patients enrolled in our prior phase II open label study as well as the 265 patients that we enrolled in enhanced so you would see likely very comparable alpine phosphatase levels.
In particular at baseline and again I think the overall demographics would be very consistent with what we've seen before.
Now your second question has to do with in terms of a reminder, around response powering I think when you look at the enhanced data in particular that we shared three months data on the primary composite endpoint used to register on calibre that would be the registration endpoint for sell at del Mar a particular.
This is the end point in which in order to be a responder a patient has to drop their alpine phosphatase level below 167 times, the upper limit of normal with at least a 15% drop in alkaline phosphatase and normal bilirubin and as you may recall the data data that we've previously presented at medical.
<unk> meetings within even just three months of treatment. We saw that 10 milligrams of <unk> resulted in about a 78% response rate on that primary endpoint.
First is about 12, 5% for those patients in placebo and that included just about 55 patients per arm. So on the primary endpoint that P value was less than 0.0001, and so it's a long winded way for me to tell you that on the primary endpoint with a 100.
93 patients randomized in response to to one sell it out of our 10 milligrams or placebo we are highly overpowered.
Demonstrate that type of an effect.
Okay.
On the key secondary endpoint with respect to alpine phosphatase normalization, so well over 90% in each of those cases.
Our target initially for 180 patients and our response was largely built around some of the assumptions relative to how many patients with moderate to severe edge. We believe we would be able to enroll in the response phase III study and so the 180 target largely filled.
An assumption around 80% at least 80% powering to show a 20% benefit or two point benefit on the impact of cell Adele par on the numerical rating scale for worst imaginable.
And the 24 hours prior period again that key secondary endpoint is largely what drove the total target in terms of patients in response.
Finally, as I think you've asked us a little bit about our dialogue with the agency with respect to.
Phase four outcome study of course approval on this primary endpoint in response as a surrogate as a surrogate endpoint is based on subpart H approval and so we do have to commit to.
Two phase <unk> outcome study, we've had in fact years of dialogue with the agency around various types of study design.
A little bit about others in the field, having challenges recruiting patients into what ultimately can be long term placebo controlled trials in order to evaluate and have enough events to demonstrate clinical benefit our dialogue with the agency has really centered around more.
Novel approaches and what we've seen with other sponsors that dialogue continues today and at the point in time in which we complete that dialogue with the agency, we will share that publicly as we approach the completion of the phase III development program and eventually initiation of a phase four outcome study I will say as mean that.
We have sponsors also recognize the importance of continuing to generate real world data registry data around the effects of our potential treatment alternative for patients with PBC versus those that are not on our treatment and we've seen others at least <unk>.
<unk> that data set very hard to see if that dataset alone is enough for a full approval I think it's important and incumbent upon sponsors like Sema Bay to really devote time and resources to generating data sets that can potentially point to this outcome results multiple different strategies.
On behalf of patients is thats, a key commitment to regulators.
Thank you so much tangible and again I cannot be so yeah Im happy for you on enrollment completion, that's we're getting.
Getting closer and closer each month to the data and thank you again.
Yeah, absolutely. Thank you guys.
Our next question comes from the line of Steve Statehouse with Raymond James. Please proceed with your question.
Thank you good afternoon I wanted to ask.
I appreciate the rundown of the market research you guys have been doing it's very helpful. I wanted to just ask about in response.
Are you comfortable with the sort of sampling you have of the different market segments you outlined.
And able to generate enough data in each of those ultimately to service a label or detailing to those segments of the market.
Yes, sure I'll start off and I'm going to ask Lewis to actually provide some additional color I think Steve clearly the first objective is in the patient population with the most significant unmet need the second line setting of course are patients who are largely incomplete or inadequate.
Anders to you'd ECA effectively highlighting alpine phosphatase levels biomarkers of cholestasis that are associated with greater risk of progression that population of course included in our response study are those that have alkaline phosphatase levels above 167 times, the upper limit of normal as you wish.
No.
That clearly is a strategy to get sell Adele par again on the market potentially for these patients and most significant unmet need.
We do see more broadly is an impact of reducing as a point estimate the percent reduction in alkaline phosphatase and patients almost independent of baseline levels of alkaline phosphatase. So the types of effects. We see in these patients that have al class above 167 times, the upper limit of normal.
We would expect to see similar percent reductions for those patients that still have elevation above the upper limits of normal that might feed in to how we think about future opportunities to expand the addressable patient population and perhaps Lewis I can ask you to add any additional color I think as I mentioned before.
One of the critical areas that we focus on certainly this biochemical response, but we would also put a focus on two other critical segments I mentioned I think that the notion of being able to address both non cirrhotic in cirrhotic patients and being able to have data to support that I think will be a very important differentiator and then probably.
One of the most important areas that we know patients really discuss consistently just this issue around provider supply.
Audio of life, and I think the opportunity toward Jeff symptom improvement will be a really important consideration as well.
And what about the what about patients that have discontinued oce in.
The marketplace. It sounds like you've done research on that and it's a very significant chunk of patients. So.
Are you going to have.
And data from response to speak to those previously exposed to or not.
Are these like even pre specified subgroup analyses for instance of the study.
Yes, another great question, Steve So in our experience even in our prior phase III study enhance we did have patients that discontinued treatment with OCA about coal to gas and we expect.
And know that we have patients even in response that have discontinued treatment with OCA as well. So we will continue to gather that data and actually have opportunities to share more of it as you know, we typically only share dataset when theres a meaningful proportion of patients that can actually provide some potential conclude.
And around that impact, but again, we've seen meaningful responses in patients and sell at El par even those that not only are inadequate responders to <unk>, but those that are also just.
This continued prior treatments such as <unk>.
And just to add in terms of numbers.
The manufacturer for our own marketplace for second line is about 30% to 35% we have seen of course with that 35%.
<unk> number of patients who discontinued therapy with OCA and we've looked at those numbers, we think that.
Probably there was about another five to 7000 patients that might benefit from selling therefore immediately who have actually discontinued therapy. So we believe that it's a very important segment for consideration upon immediate approval.
Yes.
Okay last question I, just wanted to check in on.
The number of volunteers for biopsies in the study or are you satisfied that you have enough to check the box with the FDA. There I know that was a feature of this study.
Yes. Thank you Steve we do we do believe that we have a good proportion of patients that have volunteered for biopsy in this trial based on our prior discussions with the agency.
Perfect. Thanks, so much for taking the questions.
Thank you.
Our next question comes from the line of Ed Arce with H C. Wainwright. Please proceed with your question.
Hello, everyone. This is Thomas Yip asking.
Sure.
First congratulations on the response study has completed enrollment.
So first first question regarding the response study.
Yes.
What are your expectations.
Our response study.
Orders to the property.
And also for key secondary endpoints.
LP conversation and also our prices.
Yes. Thank you for that question Thomas I think one thing to highlight is in our prior experience not only in the enhanced first phase III study conducted but again also in our phase two open label study that included just north of 100 patients enrolled we've seen a very consistent.
Response on percent decrease in alkaline phosphatase on the actual magnitude of alpine phosphatase reduction and how those reductions actually translate to the primary capital Phase II study in fact through 12 months of treatment. We saw just under 80% of patients actually meet that primary end.
Very consistent with what we saw at three months and enhanced <unk>.
Were gratified that even as we've shared some data sets for patients that have gone beyond one year of treatment. We continue to see in fact improvement in alkaline phosphatase reductions and in particular, even normalization of alkaline phosphatase going from about 40% to 50%.
30%, I'm, sorry, 40% between year, one and year two so we've seen a very consistent continued response across our prior studies.
And we'll see what we see of course in response as I highlighted it really is the same patient population. We studied in these prior trials. It's why we think this program is particularly derisked at this stage.
Patient would be to see something similar to what we've seen in the past.
Great. Thanks, Thanks for that.
Perhaps.
Another question.
Sure.
Sure.
Can you discuss what's the rough percentage of patients are for a response and also so far.
The longer treatment duration.
Patients in the study.
Yes, let me ask Chuck to give you some color, particularly on the second part of that question Yeah. Thank you Thomas.
<unk> assure began enrollment basically in.
February of last year. So the first patient to come in have come from our legacy studies. The low dose study that we published in the journal of Herpetology as well as from enhanced those patients have been accruing throughout that period right up.
To date.
And the lion's share almost all of the patients so far are coming from those legacy studies.
As you know, we announced that we began enrollment in response.
Basically in April of last year, and so we do now have a handful of patients who have completed the first year of treatment and are rolling over into into the into the <unk> study, we would expect based upon our prior experience we had really good patient retention.
And quite a significant amount of interest to participate in extension studies and so we would expect really most of those patients in response to coming to assure so.
In total this means that we're looking at.
A very large data set with a considerable amount of treatment experienced by the time, we take the data to submit.
For an NDA and we think thats really going to be helpful to regulators that need to reach a decision.
Based upon safety, but also efficacy the biochemical response, the durability and looking at the symptom relief as well.
Fantastic. Thank you for taking my questions.
So the readout next year.
Our next question comes from the line of Christian <unk> with Cantor Fitzgerald. Please proceed with your question.
Hi, good afternoon, everybody. Thanks for taking my question and let me also add my congrats on achieving full enrollment in response.
Rethought publication from the study that suggested that pruritus is observed in more patients than previously thought with PVC over 80%. So I know you were talking about some market metrics or patients who either don't respond or have tolerability issues with other therapies, but in light of some of these statistics how are you thinking.
Being an upfront second line drug.
Maybe I'll start and then Louis Ken.
Take a crack at it from the perspective of a market I.
I think I do agree that we.
Continually.
Good feedback about the importance of pruritus in the population.
Just to share a little bit related to your question our team visited over 70 clinical sites.
In terms of trying to kind of help with recruitment for response and I can tell you that time and again anecdotally we had significant comments from investigators from study coordinators in particular from physicians assistants nurse practitioners that are involved in this study.
Their patients and the need for something to address <unk> pruritus and I think youre seeing this increasingly in the literature that you alluded to and you may have heard some of the recent.
Round table symposia at.
Eagle as well as at Asl D. We're leading experts really began the discussion about the importance for physicians, who are the target audience for these presentations.
More attention to symptoms one of the issues really relates to patient care.
<unk> tend to talk about something that can only be shared by the way. They feel there's nothing currently that can be measured directly. It is only a symptom and not assign and this can be very discouraged hygiene for patients.
And I'll turn it over to Louis I think it represents a real opportunity for us to highlight that and kind of help with the entire field change that dialogue because sell at Elkhart initially seems to have.
Really nice effect on pruritus, and so thats something that will.
Important to understand and to take advantage of.
And Chuck Couldnt be more.
More profound in this description as we talked and interviewed a number of patients during our patient journey work.
We spent a considerable amount of time listening to them describe how really really difficult their daily life.
Really managing the symptom score that that'd be pruritus, whether it'd be sleep disturbance not being able to see particularly at night time, where the pruritus really becomes a lot more exacerbated and then of course, the fatigue that either is an inherent part of certainly their disease, whether theyre just not getting.
A lot of fleet because of the aging and are very very tired.
Say when we look at the numbers. If you go back whether you are a complete responder, whether youre a partial responder, whether youre an incomplete responder all of those patients whether they are on UDC, a or a combination therapy.
Many of them really suffer from this moderate to severe pruritus I would also point out of course that cirrhotic patients also have.
These symptoms as well so it is a considerable issue and.
We're very very encouraged by what <unk> could do to really support this particular population.
And Chris the only other thing that I would add.
Is that we are incredibly encouraged that solid el par as a potential treatment alternative has this effect on biochemical markers of disease that may in fact improve longer term outcomes for patients as well as this impact on improving clinical symptoms of course, there are various other approach.
<unk> is.
Being studied towards specifically addressing <unk> in PBC patients.
The real opportunity here with <unk> is to have a single agent and a very simple manner for both training physicians of course as well as patient taking a singular.
Treatment alternative that actually does both can be quite compelling we believe.
Okay. Thanks, I appreciate that.
Have your recent conference. This year you took your data and cut it in a lot of different ways showing that the results are quite consistent across different parameters.
Curious from a physician perspective, and the audience you've presented in front of it theres any component in particular that really stood out to them that you think are going to be instrumental should this be approved in your commercial conversation. Thanks again.
Well, thank you Christian.
I would maybe highlight the ability.
<unk>.
To achieve in a biochemical response safely.
Cross different stages of disease.
And this has been as I mentioned in the study visits site because it's rather that is something thats been mentioned time and time again, that's anecdotal of course, but really the ability to see it and not just patients without cirrhosis, but those patients who have compensated cirrhosis.
Compensated cirrhosis this portal hypertension and that latter category now of course has been excluded from from the approved second line therapy is no longer available that is something that I think is has the potential to be an attractive feature.
Feature because if you think about it.
Patients progress in their progressive different rates with different risk factors.
It would certainly be comforting to know that you can use use it in a patient without cirrhosis. If their disease progressed, you wouldn't be getting into dangerous territory. So we think thats something thats going to be really important to document. We've got a good data set so far and of course that we will seek to confirm that.
With response, which.
Also allowed for patients with compensated cirrhosis.
Perhaps Chris and I will ask Dennis to add any of his thoughts having also been with US had easel. Most recently along with us at our AD boards in terms of impact and responses from many of the medical community.
Sure. Thanks Rachel.
I think obviously biochemical response efficacy as well as pruritus improvement are very important features.
A good drug.
And then as well perceived by the prescribers and physicians.
Other side of the coin of course is safety and Tolerability and I think thats been probably not something thats been talked about very often but probably something that we need to emphasize because this is something that patients worry about as well as physicians.
Not only with respect with Tolerability and not having knowing side effects or debilitating side effects, but also with respect to patients who can have the compensating events such as.
Cirrhosis or other complications of cirrhosis and there seems to be a little bit of a halo effect in that that we've studied cirrhotic patients in the past and we're continuing to study these patients and it appears so far that the <unk>.
<unk> is being well tolerated in these patient groups.
Prescribers recognize that these are sick patients that can have the compensating decompensation events at any given moment.
So they don't want to use a drug that could they could.
Add to that risk.
I think we have a drug and fell about par that that can mitigate some of these risks we will see if the data supports that but I think thats. Another factor that prescribers appreciate that and worry about that I think hopefully we can meet with our database.
Thank you.
Our next question comes from the line of my ankle Pantani from B Riley Securities. Please proceed with your question.
Good afternoon, Deane, thanks for taking our questions and congrats on over enrolling this fund so just maybe a quick follow up for Dennis.
Could you comment on the response screening failure rate I was just curious how much of those.
Also in <unk>.
Adequate responders on meeting this clinical trial data help outlaws bilirubin.
Comp is it could you just comment on that and then I will follow up for Chuck.
Sure so our.
Screen failure rate has been very consistent from our prior experience.
As you can imagine there are a huge list of inclusion exclusion criteria for any of the study.
The response study design was almost identical to that of enhance.
We predict that going in what our screen failure rate would be and it turned out to be pretty much online with what we actually saw.
It's not inconsistent with general other clinical trials that you may see.
They range from anywhere from 40% to 60% screen failure rate, sometimes it can go up to 75% or 80% depending on the.
On the on.
On the inclusion and exclusion criteria and how much how much demand there is for these type of.
Comorbidities in biochemical responses or biochemical status.
So <unk>.
<unk> results of course are usually the most common cause for exclusion meeting exclusion and Thats. What we saw in this in this response screening effort as well.
So thats very consistent with what we've what we've seen in the past and consistent with other trials that we've been conducting we've conducted.
Got it thank you and Chuck of coming away from the Eagle.
Ed.
Much of this anti fibrotic component.
Do you intend to study further.
I also ask I mean.
Ask it for a couple of reasons.
Your comments on cirrhotic population from a safety standpoint is interesting but also.
Getting to that outcome is confident in converting the accelerated approval to full approval.
Is there.
And evaluation more you could do to understand how good overnight fibrotic drug. This is giving you a national votes.
Yes. Thanks for that question I think that's really important.
Trying to build upon.
And science.
What we learned in the Nash study and take that and apply it.
A little bit different of course, we do have biopsy in this study and we may learn a bit there around.
The effects on fibrosis.
It's a relatively.
Short term, it's a year and of course, there won't be.
Every patient.
We will have a biopsy there is an emerging approach so that was just recently.
Published in the journal of Herpetology, that's getting increasing attention, which looks at liver stiffness using.
Fiber scan methodology, which is basically transient elastography.
Thats been correlated with histological stage of disease. So this was a paper.
Led by Christophe Corpus show, and we're including fiber scan measurements.
Both response and assure and we're very interested in understanding how these might be used in clinical research is potential markers for outcomes.
Perhaps.
Currently the case, but in the future it might be that regulators might consider them.
But also in medical practice.
Scan technology as more and more are being widely available it's really part of general practices large Gi practices obviously.
University of academic medical centers, but even so Britain with hospitals and the like.
And yes.
It's also being extensively used in Nash, so we're able to kind of ride the tailwind.
For its wide availability.
We think that looking at liver stiffness as.
To confer effects on fibrosis.
Lack of progression.
Looking at cereal.
Minutes or even hopefully regression.
Could be a wave of the future and that could be important for a drug like <unk>.
Has anti fibrotic effects.
Thank you and my final question is about the open label hepatic impairment study Youre running.
Can you just provide us update on that in and just confirm are you just exploring that then mid dose level of <unk>.
Lower doses of that.
Now, let me ask Dennis to provide you. Some additional color here. This is obviously a study as you mentioned hepatic impairment study in patients with PBC. So that we can better understand particularly safety, but also efficacy in more advanced patients and these are those patients that have either child Pugh a car.
<unk> cirrhosis, and a small subset of patients with child, Pugh B and C. D compensated cirrhosis and so perhaps I'll, let Dennis give you just some high level on this mine like this is an ongoing study and so the point at which we complete the trial we'd share updates in terms of data from the trial, but Dennis perhaps you can give a little bit more color around the trial itself.
Sure. Thanks for the question, Matt. Thanks also through Gopro the preamble.
As usual is exactly right you have a patient that were looking for in the study, it's an ongoing study, which for which we don't really make.
Too much detailed comments suffice to say these patients are rare patients because EBIT, especially CPB patients and then EPA patients with.
Portal hypertension pension are also fairly rare.
Making progress in recruiting patients into the study and activating additional study sites we.
We do have.
Fairly long timeline before we have to complete the study.
So we are planning to be able to include this database into the NDA. We are testing 10 milligram dose, but we remain we maintain the flexibility of going to a lower dose if we see.
<unk> metabolism, and pharmacokinetic exposure in patients with advanced cirrhosis, which would require a lowering of the doses. So we do have that flexibility and we'll let you know how that goes once we finish the study.
Thanks for taking our questions.
Thank you Mike.
Our next question comes from the line of Patrick <unk> with lifestyle. Please proceed with your question.
Hi, This is Corey on for Patrick Congrats on the enrollment and thanks for taking our questions.
First one from US you recently had some great data regarding Philadelphia has effect on globe score.
Obviously, Philadelphia has a strong potential for a differentiated label in regard to pruritus, but is there eventually and opportunity for <unk>.
That might include outcomes for globe score in to what degree do regulators and clinicians gift.
Give credence to globe.
Given that its a predictive metric.
Yes, Thank you Corey.
So the globe score is a continuous measure of risk that's been validated to predict outcomes. This is based on work from the global PBC study group.
It includes the elements that go into it are age and then laboratory parameters, which wouldn't be alkaline phosphatase and bilirubin platelets in albumin levels and those are all liver parameters to it.
Really speak to the health of the liver overall and so the value of it in clinical research is typically used in medical practice. If there is a there is a web page you can go to in a position Ken just input.
The parameters based on the laboratory results.
Get a get an idea of what's going on with the patient maybe you look at there is these measures serially so with typically used to kind of.
PVC specific risk assessment, so the the <unk>.
Many physicians can make some medical judgments.
Any anything that needs to be done any adjustments to treatment. The way that we are using it as is.
Our variable to examine treatment response and it has several advantages I think over the categorical variables the one.
Ones that for example, regulators who are using right now we've either respond or don't respond.
And that doesn't really give a lot of granularity so very much a blunt interest instrument, especially in clinical research so having a continuous variable allowance for finer gradation and judging risk and also for examining treatment differences between the two groups. So that's another powerful.
Measure I think that at the moment as far as our program is concerned we're.
Using a precedented endpoint.
And EMA accept it we're not going to change that.
The globe score is.
The exploratory parameter we can use it to tease out differences for example between post hoc analysis between subsets I would say, though that this paper that I mentioned earlier from Christophe corporate show.
As proposed combining the liver step this was fiber scan with the globe score as a potential for regulators to use as an outcomes measure in studies were.
We're not prepared to do that quite yet, but I think thats could be a direction that the field goes it could be quite important so personally I am quite excited about the globe score I think it gives you a lot of insight and information. If you had an opportunity to see our presentation you can see the different ways, we can dissect the parameters there.
Response, and also it was encouraging that through two years almost every patient had a response had an improvement I think 94% of patients at.
Of the 50 patients at two years improve their <unk> scores.
That's something to pay attention to.
Got it and last one from US given that response has enrolled about 193 patients across about 160 active sites, how does the distribution of patients across sites.
<unk> to that of enhance and are there any regions or sites that are particularly enriched or deficient for patients.
That's a good question Corey, perhaps I'll just answer that one and if there's anything I Miss Dennis can add onto it not dissimilar from enhanced first of all the majority of patients of course come from the U S. Given the site distribution in the number of sites we have in the U S.
But I actually think we have very good representation globally in Europe .
In Asia as well as in particular in this case South America.
So there were certainly some countries in which we saw more of a contribution and enhanced.
Countries in fact in response that May in fact have been impacted more so by COVID-19 restrictions across the 18 months that we are enrolling response.
Those restrictions perhaps were lighter in some other regions and we continue to build in terms of relationships. There are many overlapping sites from our prior enhanced study, but there are many new sites and relationships and partners that we build even with respect to response and so I think we actually had very good distribution across all of those.
<unk> in particular, Europe , Asia, and particularly South America. In addition to again the majority of patients coming from the U S.
Excellent.
That's all we have congrats again and thanks for taking our questions.
Thank you.
Our next question comes from the line of Thomas Smith with <unk>.
B Securities. Please proceed with your question.
Yes, hi, everyone. This is Mike on for Tom. Thanks for taking my question as you start to think about the transition to commercial operations, what kind of information do you hope to present timber your upcoming virtual Investor day.
Typically on some of the initial learnings that you've found.
What metrics do you expect to track.
Move forward with the launch.
Yes. Thank you for the question, Yes, we're looking forward to September I think one of the things we want to try to do is take a bit more of a global view to all the planning that we've done and share some of the data that we have on both U S. Ex U S. Geographies. We also are examining the payer landscape here in.
The U S. We've already done some work in Europe , we'll share a little bit of that to.
You want to just talk a bit about both the commercial and government coverage landscape here and what we can expect around those issues and I think the other thing I'll say is we are hoping that our go to market strategy formation that will stand up here in the second half of the year will go also to inform both not just our commercial.
Commercial work, but also obviously, our medical affairs focus as well so I think the way we will look to measure and evaluate things sure. We'll have a lot to do with our engagement with Kols and and how we'll go about engaging payers here in the pre commercial setting to really begin to articulate our value proposition.
So more to come on a lot of that but we're really.
Getting into a bit more detail here in the next few weeks.
Understood. Thanks, very much for all the color.
Thank you.
There are no further questions in the queue I would like to hand, the call back to management for closing remarks.
Thank you operator, as we look ahead to the remainder of the year. We will continue to focus on execution of response and all of the ongoing active studies being conducted to prepare ourselves for future regulatory submissions.
So the efficacy and safety data in our ongoing studies reflect what we've observed in our prior phase II and phase III studies, we believe cell Adele bar as we've mentioned has the potential to significantly improve the lives of patients with PBC.
I think it bears repeating we continue to believe the development program remains one of the most robust and derisked in this indication today we.
We see many opportunities ahead of us to unlock near term and long term value from sell at alpine and PVC and look forward to sharing future updates as we make progress.
We look forward to sharing more about our story and this opportunity during our virtual Investor day on September 22nd that Lewis spoke about.
I'd like to thank everyone. Once again for joining our call today and we look forward to speaking to you again very soon.
Ladies and gentlemen, this does conclude today's teleconference. Thank you for your participation.
You may disconnect your lines at this time and have a wonderful day.