CymaBay Therapeutics, Inc. (NASDAQ:CBAY) Q4 2022 Earnings Conference Call March 16, 2023 4:30 PM ET
Paul Quinlan – General Counsel
Sujal Shah – Chief Executive Officer
Chuck McWherter – President, Research & Development and Chief Scientific Officer
Lewis Stuart – Chief Commercial Officer
Dan Menold – Vice President, Finance
Conference Call Participants
Yasmeen Rahimi – Piper Sandler
Steven Seedhouse – Raymond James
Kristen Kluska – Cantor Fitzgerald
Ed Arce – H.C. Wainwright
Jay Olson – Oppenheimer
Julian Harrison – BTIG
Good day ladies and gentlemen and welcome to CymaBay’s Fourth Quarter and Full-Year 2022 Financial Results and Business Update Conference Call. [Operator Instructions] 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 CymaBay website at www.cymabay.com.
And now, I would like to turn the call over to Mr. Paul Quinlan, General Counsel at CymaBay. Thank you Mr. Quinlan. Please proceed.
Thank you operator, and good afternoon everyone. I hope that you have had a chance to review the press release we issued announcing our fourth quarter and full-year 2022 financial results and business updates. You can access that release on our website under the Investors tab.
Joining me on the call today are Sujal Shah, Chief Executive Officer; Chuck McWherter, President of Research & Development and Chief Scientific Officer; Lewis Stuart, Chief Commercial Officer; and Dan Menold, 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 CymaBay’s expected future performance, business prospects, events or plans, including clinical plans, regulatory approvals, funding and repayment schedules, anticipated timelines and data release dates, cash runway and planning for manufacturing and commercialization are forward-looking statements as defined under the Private Securities Litigation Reform Act of 1995.
Although CymaBay 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. CymaBay 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 CymaBay’s 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 of CymaBay and any recording or rebroadcast is expressly prohibited without the written consent of CymaBay.
At this time, I’d like to turn the call over to Sujal.
Thank you, Paul. Good afternoon and thank you for joining us today. We finished 2022 with significant progress in our Phase 3 program for seladelpar in patients with primary biliary cholangitis or PBC. In parallel, we were establishing our readiness for its commercial manufacturing and also creating our pre-launch infrastructure and go to market plans.
Importantly, we delivered through presentations and publications on our foundational commitment to understand the science of seladelpar’s potential for action on disease, improvement in symptoms, and confirming its effects after long-term treatment on serum biomarkers linked in the literature to improve transplant-free survival.
We didn’t rest on our laurels with those 2022 accomplishments. We came fast out of the blocks in 2023 with licensing Japan rights to seladelpar providing significant upfront cash, followed closely by a significant capital raise at a favorable valuation. By the end of January, we had strengthened our balance sheet by over $125 million to meet our planned operating cash needs 12 months beyond top line Phase 3 RESPONSE results expected in the third quarter of 2023.
In short, we’ve set the stage to execute on our 2023 objectives to potentially transform the company by placing us on the doorstep of an NDA submission. And if successful, approval of our first product. Our prepared remarks today will be focused on key business updates centered around substantial advancements in the company’s clinical development program of seladelpar for patients with PBC, organizational growth and focus necessary to bring seladelpar to patients, and financial position to support value creation for all of our stakeholders.
At the core of our clinical activities, our two active global clinical trials, RESPONSE and ASSURE that are part of one of the most robust development programs ever conducted for patient with PBC.
I’ll ask Chuck McWherter, our Chief Scientific Officer and President of Research and Development to start the call today with an overview of our clinical accomplishments over the past year, including presentations made at DDW, EASL, and AASLD last year and the latest progress on development activities.
In addition to clinical progress, the past year was importantly defined by critical infrastructure and organizational growth necessary to enable the transition of our seladelpar clinical program to a commercial effort aimed at improving the lives of patients with PBC.
I will speak today about our business development efforts that led to our partnership with Kaken in Japan; CMC, regulatory, and quality priorities to enable NDA filing; and balance sheet growth positioning us with a cash runway beyond key catalysts in the second half of this year.
I will ask Lewis Stuart, our Chief Commercial Officer to also outline critical progress in pre-commercial planning that kicked-off in 2022 and will continue through this year. We’ll end today’s call with Dan Menold, our VP of Finance, who will provide an overview of our financials during the fourth quarter and full-year 2022 before taking questions. Chuck?
Thank you, Sujal. We made tremendous strides in 2022 marked by important accomplishments in our clinical development program and multiple data presentations made at three key medical meetings. The progress we made reflects our commitment to bring seladelpar to patients with PBC, through well-designed studies to understand its efficacy and safety.
We believe that understanding the mechanistic underpinnings on the observed improvements and studies to date in markers of cholestasis, liver injury, inflammation, and pruritus is vital to gain the confidence of all our stakeholders, including the medical, regulatory, payer, investor and most importantly, patient communities.
In addition, we organized and streamlined the oversight of our R&D function and decision making. We recruited seasoned talent in clinical development and operations, biometrics, manufacturing, regulatory and quality, and medical affairs. Filling out our R&D capabilities, while simultaneously executing on seladelpar in development, was an imperative to enable meeting our goals in 2023.
As the Omicron variants created a significant drag on the execution of clinical research across the globe, we mounted an aggressive on the ground White-Glove recruitment effort for RESPONSE, our global Phase 3 registration study of seladelpar in PBC. The CymaBay team hit the road conducting face-to-face interactions with personnel from about 70 sites, with site visits and focused mid-study investigator meetings.
We provided hands-on solutions for recruitment with two-way communication that we believe visibly demonstrated our commitment to our worldwide network of investigators. By the end of July 2022, the study enrolled 193 patients meeting the eligibility criteria of an inadequate response or intolerance to ursodeoxycholic acid, patients were randomized 2:1 to daily oral seladelpar 10 milligrams or placebo. We expect to report top line data from this study in the third quarter of this year.
In 2022, we also made significant progress advancing the ASSURE open-label extension study that today includes over 200 patients from our prior clinical studies and from response taking seladelpar once daily. Inclusive of these two ongoing studies and across our entire development program, we expect to have over 600 unique PBC patient experiences, majority of which will have had anywhere between 1 years to 3 years of experience on seladelpar by the time we plan to apply for regulatory approval.
We believe that another significant aspect to ASSURE is that a majority of sites along with a significant proportion of patients from prior studies elected to participate in it, providing us encouragement regarding their prior experience with seladelpar. We had significant presence at three major medical meetings in 2022.
At the annual Digestive Disease Week held in San Diego last May we’ve had an oral presentation in the Presidential plenary session on the impact of seladelpar on predicted survival after two years of treatment. We also had two posters that received conference poster of distinction awards.
One presented a pooled analysis of patients with compensated cirrhosis and the other examine the effect of seladelpar on biochemical response and safety in patients with prior experience with obeticholic acid and fibrates.
At the EASL conference held in London last June, one of our main meeting highlights was an oral presentation by our collaborator, Professor Bernd Schnabl from The University California San Diego. He described studies established in the seladelpar acts through PPAR delta to suppress bile acid synthesis by upregulation of FGF21 in hepatocytes. This result explains at least in part, its anti-cholestatic effect.
Importantly, his research established that seladelpar suppression of bile acid synthesis is via an entirely different pathway than that of FXR agonists, such as Ocaliva. Additional presentations at this meeting reported comparable safety and efficacy in a pooled analysis in patients with and without compensated cirrhosis. And a detailed mechanistic investigation, of seladelpar’s ability to reverse established fibrosis in mouse injury models, where it was found to provide greater FX than either an FXR agonist for a thyroid hormone beta receptor agonist. Both of which are in active development for fibrotic liver disease.
Traditionally, flagship meeting for us is the Liver Meeting hosted by the American Association of Liver Disease. Held in November of last year in Washington DC, we had two new presentations of clinical results for seladelpar in PBC. The first was a poster reporting on a post-hoc pooled analysis of lipids from the seladelpar open-label Phase 2 and Phase 3 ENHANZE studies in PBC.
Dyslipidemia is a common feature in PBC and so we were interested in understanding how lipids were affected by seladelpar treatment in PBC patients. Changes in lipids were analyzed for 373 patients with PBC receiving daily oral treatment with placebo, 5 milligram or 10 milligrams of seladelpar at 1, 3, and 6 months. The majority of these PBC patients had dyslipidemia with 77% being above normal total cholesterol levels, and 54% with elevated LDL cholesterol levels.
Seladelpar treatment resulted in dose dependent decreases in total cholesterol and LDL cholesterol. And these changes were significant for those taking seladelpar 10 milligrams versus placebo. Interestingly, these effects were similar for the approximately 25% of patients on a background lipid therapy, compared to those who were not. Metabolic risk is a common characteristic in this population and the profile of seladelpar seen thus far is encouraging in this aspect.
A second clinical presentation was made by the CymaBay research team describing an analysis of the Serum Metabolome of 160 patients completing three months of treatment in the ENHANZE study. This analysis found broad dose dependent changes in the unbiased survey of 1,474 metabolites. Seladelpar was found to increase serum markers of mitochondrial and peroxisomal fatty acid beta oxidation, indicated by increase in carnitine, and acyl carnitines and decreases in dicarboxylates and significant reductions reduced serum levels of inflammatory lipid mediators, including long chain fatty acids, mono and diacylglycerol, eicosanoids, Ceramides and Sphingomyelins.
Measured in our target PBC population, these results provide clinical evidence of seladelpar’s impact on mitochondrial function, as well as reductions in the serum of known inflammatory mediators. In 2022, two important peer-reviewed publications of results from the Phase 2 52-week dose ranging study of seladelpar in adult patients with PBC receiving seladelpar as add-on therapy to first line ursodeoxycholic acid or as monotherapy to the patients intolerant to UDCA were published.
The first paper published in the Journal of Hepatology with the Lead Author Professor Chris Bowlus describes the treatment response and patients enrolled with a minimum serum alkaline phosphatase level of 1.67x the upper limit of normal or 194 units per liter. And these patients were on average in excess of 318 units per liter. Seladelpar was studied at 2, 5, or 10 milligrams for 12-weeks, after which doses could be increased up to 10 milligrams if needed to improve treatment response. Cirrhosis was present in 21% of patients and 71% had pruritus at baseline.
At week 52, the composite biochemical response of ALP and bilirubin rates in patients initially randomized to 5 milligrams and 10 milligrams were 53% and 67%. ALP normalization rates in these cohorts were 13% and 33% respectively. The pruritus visual analog scale was also decreased in the 5 milligram and 10 milligram cohorts. There were no treatment related serious adverse events and four patients discontinued due to adverse events.
A companion paper appeared in print and liver international last year reporting the effects of seladelpar treatment in this study on patient reported symptoms of pruritus, sleep, and fatigue through one-year of treatment. In patients with moderate to severe pruritus, substantial improvement in pruritus was seen in 58% and 93% of patients in the 5 milligram and 10 milligram cohorts respectively.
After one-year, patients reporting the improvement substantially outnumbered those who worsened in the total 5D itch scale and PBC-40 itch and fatigue domain questionnaires. Improvement in sleep disturbance at one year was reported in 81% of the 5 milligram cohort and 78% of the 10 milligram cohort in those patients with baseline itch related sleep disturbance by the 5D itch score with similar results using the PBC-40 sleep questionnaire.
Seladelpar treated patients had significant reductions of 46% in the 5 milligram cohort and 31% in the 10 milligram cohort in the serum bile acid precursor C4 and reductions of up to 38% in serum bile acids. Improvements in liver biochemistry and patient reported symptoms were generally confirmed at three months in the Phase 3 placebo controlled ENHANZE study, which we have now submitted for publication.
Finally, I want to recognize our medical affairs team as we increased our effort to broaden engagement and scientific exchange with PBC key opinion leaders, our other healthcare providers and advocacy groups. Sujal?
Thank you, Chuck. We made great strides supporting our overall goal to bring seladelpar to patients with PBC, along with the important progress in clinical development that Chuck highlighted. I’ll walk through a number of areas of progress that are vital to our future success.
First, our business development activities have been focused on evaluating potential partners who can help us bring seladelpar to patients around the world, particularly in geographies outside the U.S. and Europe where additional development beyond our ongoing clinical studies will be required.
In January, we were thrilled to announce our partnership with Kaken pharmaceutical company to develop and commercialize seladelpar for patients with PBC in Japan. Kaken is a recognized leader in pharmaceutical industry in Japan with a strong history of scientific and medical innovation and a clear focus on improving the quality of life for patients.
In exchange for the exclusive license to develop, commercialize, and market seladelpar in Japan for PBC, CymaBay received an upfront payment of $34.2 million and will receive potential milestone payments totaling up to [JPY17 billion] [ph] approximately $128.4 million at current exchange rates for the achievement of certain regulatory and sales milestones in addition to [20-plus percent] [ph] net effective royalties.
Kaken will be responsible for development, regulatory approval, and commercialization of seladelpar in Japan. There are currently no approved second-line treatments for PBC in Japan. We could not have found a better partner who shares our values and our passion for the potential of seladelpar to significantly improve care and quality of life for patients with PBC and are excited to see this work advance.
Key activities related to CMC, regulatory and quality functions are all crucial as our clinical development program progresses. Our teams have been ensuring that we are prepared to quickly file for regulatory approval should we confirm the efficacy and safety profile of seladelpar in our ongoing clinical studies. And to supply seladelpar should we be successful at gaining regulatory approval.
These efforts are vital to our overall success and remain on-track for us to accomplish our objectives as the program progresses. Another very important work stream has been pre-commercial planning.
I’ll hand the call now to Lewis Stuart, our Chief Commercial Officer to outline key initiatives in this area. Lewis?
Thank you, Sujal. In 2022, our commercial focus was on assessing seladelpar’s global market opportunity while conducting foundational market research and analysis within prioritized to region geographies. Our global market evaluations included both primary and secondary research across all key stakeholders, including PBC patients, while also examining healthcare providers perceptions of current PBC treatment versus seladelpar’s target product profile.
It was equally important that we conduct market access landscape research in the U.S., Europe, and Japan as a means for defining the value proposition, reimbursement strategies, and optimal coverage pathways for each regional geography. As you may recall in September, we held a PBC Analyst Day, where I shared a summary of our findings, highlighting insights from our U.S. based research.
As I mentioned during our last earnings call, these global insights from patients, healthcare providers, and payers have aided in the development of our core strategic imperatives with the goal upon approval of achieving widespread patient access to seladelpar.
In Q4 2022, we developed our initial global go to market strategy. And today I would like to share some of the essential themes from these plans. CymaBay’s commercial vision, will be driven by a laser focus on PBC and its stakeholders, utilizing a high touch engagement model that is supported by scientific rigor and innovation.
Our partnership with healthcare professionals is to support this pursuit of an enriched quality of life, coupled with the potential to demonstrate improved health outcomes, but their PBC patients. Our success in achieving this vision begins with the science of seladelpar, and its potential for resetting the ideal goals for PBC treatment with a greater portion of patients experiencing biochemical normalization, along with the alleviation of symptom burden.
Our research shows that these new goals could significantly expand the second-line market opportunity, while improving each stage of a PBC patient’s overall treatment journey. Furthermore, our previous Phase 3 clinical study results from ENHANCE gives us confidence in seladelpar’s promise of becoming an optimal solution for changing the future PBC treatment paradigm.
You will recall that in ENHANCE we observed higher biochemical responses and normalization rates for ALP and ALT, significant improvements in moderate to severe pruritus demonstrating these, as well as other efficacy and safety measures in both non-cirrhotic and compensated cirrhotic patients.
A second theme to seladelpar’s success will be maximizing patient access and compliance. Our U.S. market access landscape research reveals payers preference for seladelpar’s target product profile over that of obeticholic acid. Other analysis indicates consistent coverage of OCA in recent years, reflecting our confidence in seladelpar experiencing similar if not improved coverage.
Moreover, the recent announced drug coverage enhancements for Medicare eligible patients could provide tremendous relief in out of pocket cost, including in many cases the elimination of monthly co-pays. Our development of a high-touch service model will be designed to support each patient’s access to seladelpar, as well as their overall treatment experience.
A third strategic theme of our go-to-market plans will be to maximize seladelpar value in the U.S. by leveraging local expertise through partnerships in ex-U.S. prioritized regions. The recent announcement of our collaboration with Kaken in Japan is an example of this endeavor and we are actively engaged in partnering discussions for other markets, including Europe.
Let me now turn the call over to Dan to summarize our financials for the fourth quarter and full-year 2022. Dan?
Thank you, Lewis. As others on the team have highlighted, during 2022, we focused our resources on executing the patient treatment phase of the fully enrolled response study and continuing enrollment of the ASSURE study. We also continue to advance other required clinical and regulatory activities necessary to complete our late stage development of seladelpar in PBC.
And finally, we made further progress in manufacturing, as well as in medical affairs and commercial where we continue to plan and prepare for potential future launch of seladelpar in PBC.
From a financial perspective, we finished the year with a strong balance sheet with cash, cash equivalents, and investments totaling $135.5 million as of December 31, 2022. We further enhanced our cash position in January 2023 following the receipt of a $34.2 million upfront payment from our Kaken collaboration and the completion of a $94.2 million public equity offering.
Overall, we believe that our year-end cash and investments on-hand together with the upfront Kaken payment and equity offering proceeds received in January 2023 will be sufficient to fund our operating plan through the third quarter of 2024.
I will now turn to a review of our fourth quarter and full-year operating results. Research and development expenses for the quarters ended December 2022 and 2021 were $16.2 million and $18.4 million respectively. Research and development expenses in the quarter ended December 2022 were lower than 2021, primarily due to the completion of the enrollment phase of the RESPONSE trial in July 2022 and lower spending in other Phase 1 NDA enabling clinical studies.
Research and development expenses for the years ended December 2022 and 2021 were $68.0 million and $64.5 million, respectively. Overall, these expenses were higher in 2022 due to a $5.6 million in internal costs, which rose to $26.4 million as we added research and development personnel to support our late stage clinical studies in PBC. This increase in internal costs was partially offset by a slight decline in external development costs related to our CROs, CMOs, and other clinical and preclinical study vendors.
Specifically, these external development costs decreased by $2.1 million to $41.6 million, due primarily to the completion of enrollment of the RESPONSE trial and lower spending in other clinical studies during 2022. As we continue to progress late stage development of seladelpar 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 December 2022 and 2021 were $7.2 million and $6.1 million respectively, and for the years ended December 2022 and 2021 were $25.1 million and $23 million respectively.
General and administrative expenses in the quarter and year ended December 2022 were higher than the corresponding periods in 2021, due primarily to the hiring of additional personnel to support our corporate growth.
Overall, our net loss for the quarters ended December 2022 and 2021 was $26.6 million and $26.5 million or $0.30 and $0.34 per share respectively and net loss for the years ended December 2022 and 2021 was $106 million and $90 million or $1.21 and $1.27 per share respectively. Net loss for the full-year 2022 was higher than 2021, due primarily to an increase in research and development and general and administrative expenses, as well as an increase in net interest expense related to our Abingworth development financing agreement.
Overall, we expect our operating expenses to increase in the future as we continue to execute our development plans for seladelpar and PBC.
Let me now hand the call back to Sujal.
Thank you, Dan. We could not be more excited about the year ahead of us at CymaBay. While we are proud of our recent accomplishments, we have much more to do ahead of us, as we maintain our laser focus on being an innovator and a leader in improving the lives of patients with PBC.
We have assembled a committed and talented team here at CymaBay to bring our Phase 3 program to completion and submit for regulatory approvals, but also to begin key initiatives in medical affairs pre-commercial planning and life cycle management. We also continue to invest in understanding seladelpar’s effects in PBC and believe there is more to its potential benefits that have yet to be fully appreciated.
Having worked with healthcare providers and patient advocacy groups in PBC since 2015, we believe we are well-equipped to be an innovator in this disease for years to come. We are grateful for their partnership as we approach a transformational year ahead at CymaBay for all of our stakeholders, most importantly patients.
We’re now happy to take questions. Operator?
Thank you, sir. [Operator Instructions] And our first question comes from the line of Yasmeen Rahimi with Piper Sandler. Please proceed.
Good afternoon team, and congrats on all the great progress, and we’re really looking forward to the data. Few questions for you. One of the feedback we have been getting as we speak with PBC [indiscernible] is how the entire PBC community is moving forward towards alkaline normalization rather than [1x 6, 7] [ph] the upper limit. So, I would love to ask the question with that, have you – what does your market research say in terms of, you know, what percentage of the physician community are moving forward towards that goal? And then maybe some color on how the guidance is written or if they’re going to be updated because obviously that will substantially increase the market size? So, that’s sort of bucket 1.
Bucket 2 is, Sujal, I’m certain that strategic interests have been high and will continue to be high and a question that we’re getting is, how do you weigh the pros and cons of M&A before or versus after data? And then the third one is, for Chuck in regards to the Glove service that was provided through RESPONSE, we recognized that that really helped expedite the enrollment, but could you, maybe put in context how dose measures reduced heterogeneity and maybe ensure really a success, further success, some of the nuances? Sorry for the long question, and I’ll jump back into the queue. And thank you for taking them.
Thank you for the questions. Yes. Let me start-off and of course I’ll ask Chuck to add as well. Your first question was around treating patients to normalization with respect to biochemistries and particularly alkaline phosphatase, a liver enzyme that’s been associated with progression of disease and a reduction of which has been associated with reducing the progression of disease and particularly improving transplant free survival.
In terms of our discussions, yes, I think as we’ve had conversations with many of the healthcare providers and particularly the thought leaders in the field globally, there’s no question that as potential agents like seladelpar where in our clinical studies to date, we’ve seen anywhere from 30% to 40% of patients enrolled in our prior studies between 1 years and 2 years of treatment actually experienced normalization of alkaline phosphatase.
There’s no question that there’s a push now to think about treating patients really to normal biochemistry. It’s not something that [HCPs] [ph] I would tell you have been able to really focus on in the absence of potential treatment alternatives that bring a good proportion of patients to normalization. The historical data sets that have been gathered among many of the databases, global PBC study group, but others as well, you know do in fact point to an increased benefit with respect to transplant free survival not only when you bring alkaline phosphatase levels lower, but when you actually bring them into the normal range.
So, this association is one in which I think there’s much greater appreciation from healthcare providers. And over time, we think a greater appreciation from payers and the community at large. And we think this is one of the potential advantages that seladelpar has.
Chuck, anything to add?
No, I think that’s a pretty good summary, Sujal.
So, I think the other part of your question then the second part of it, yes, was around – the pros and cons around M&A. First, let me be clear. We’re really building CymaBay to have all of the functional talents and experience to bring this drug to patients ourselves.
We are committed to this path forward in PBC as we talked about in some of the prepared remarks. We’re committed to better understanding the effects of seladelpar on the disease even beyond what we know today. And in that path forward, we certainly believe we have not just the internal resources, the relationships with key healthcare providers, but really the balance sheet and investors to allow us to accomplish this objective as we think being able to bring seladelpar to as many patients that may benefit as something we can execute upon ourselves and firmly believe this is the greatest path to creating significant value.
That’s how we think about operating the company. When it pertains to strategic interest, obviously, we have a fiduciary responsibility that we do not ignore recognizing the potential benefits of either partnership or M&A are absolutely always part of our calculus. In terms of partnership, I will at least say this.
The Kaken partnership in Japan is one in which we firmly believed it will now accelerate the path forward. This is an area in which there’s additional clinical activities required to bring seladelpar potentially to patients with PBC in Japan. With the balance sheet we have today, with the response study and the overall program that we have today, we think that we have the ability to register seladelpar in the U.S. and potentially in Europe as well on our own.
And we’ll continue to evaluate partnerships, particularly outside the U.S. over time, but we’re in this position where we can execute on the near term objectives here as we get to data. And we’ll think very closely about those alternatives that may present themselves to us thereafter.
Yes. And just to get to your question, Yas, about the outcome or the benefit that we saw in terms of the outreach that we made. We sent team members across North America, Europe, Middle East, even to Asia for the site visits we held, the investigator meetings. The impact of that, Yas, to the enrollment, but also it’s about relationship.
It’s – we’re able to get feedback real time in terms of the clinical experience that physicians have. And what I think you may be getting at this, what do we think in a qualitative sense this is going to translate into? It’s really, I think increasing the probability of high quality data. We have relationship if there’s findings that need to be discussed, if there’s cleaning and locking the database, being having them be responsive, responding to us, having the ability to reach-out directly to them and importantly, being efficient in the process. Not letting things drag out.
I think that’s really the implications in my mind from having so many different contacts with clinical sites in our study. I think for a rare disease, this is really important.
Thank you so much for all the great color.
And the next question comes from the line of Steven Seedhouse with Raymond James. Please proceed with your question.
Great. Thanks for taking the question. It seems to us that in addition to the primary endpoint, there is some secondary effects of the drug, including on pruritus of course where you could really differentiate seladelpar from other competitors [Technical Difficulty] [ph] market potentially. So, I had a couple of questions about those and I just wanted to, sort of drill down into them.
So, the first is just on like the quality of life measures fatigue and sleep disturbance. So, the PBC-40 scoring system, are you measuring these as secondary endpoints? Do you have any expectations for demonstrating improvement on those? And then same question basically for liver function test ALT and AST, is this something you’ll quantitatively look to show benefit on in RESPONSE?
Yes. Thank you for the questions, Steve. Maybe Chuck, you want to give some commentary?
Yes. So, I think it’s a very good observation, Steve. Appreciate that. As you may know from our Liver International paper, which was an – and as you may know from our Liver International paper, which was an open label study, we did show improvements in those measures in the PBC-40 the sleep disturbance domain, as well as in the [indiscernible] sleep measures as well. And then on fatigue, in that study that was a paper diary driven assessment in enhanced and now in RESPONSE, we’re also measuring those as well as you – that’s the answer to your question. But we’re using that electronic diary. So, we’ll collect that data at frequent intervals.
And I think they are secondary endpoints. They’re not statistically powered, but I do expect that they’ll be something that we’ll be very interested to see what the impact to seladelpar to see if we can see a consistent pattern. We’ll just have to wait and see.
The only other thing I’d add to that Steve is, from a broad perspective with respect to the program overall, even as we approach top line data in RESPONSE, we’re very focused in continuing to understand these effects in PBC patients even beyond the Phase 3 study. So, of course measuring pruritus, collecting PBC-40 and understanding the potential effects of seladelpar on fatigue and sleep disturbance and even looking at the effect of seladelpar on liver enzymes, including ALT in particular, I think a support for how anti-inflammatory this mechanism is.
These are all areas in which we continue to dig and continue to invest resources because we do agree with you. These may be very significant differentiating features, not just from existing treatments for patients with PBC, but potentially from other treatments that are in development currently as well. And so, you’re going to continue to see us invest in these areas in particular.
And as we’ve done really since 2015 when we first started developing seladelpar for patients with PBC, anything that we learned through this additional work, we would look to share at medical meetings and eventually publish as we have done historically.
That’s great. I just want to ask about the pruritus endpoint as well, obviously given how important that is and you guys may be able to separate yourself from the pack there. So, just specifically on how it’s – first, I’m curious if you can share like the proportion of patients in the study you expect to qualify for the analysis based on the baseline NRS greater than or equal to 4 criteria?
And then, this is measured I believe is a weekly average at a 6-month time point. And I’m just curious, logistically how that works, if that’s sort of the weekly average of every measurement from day 0 to month 6, or is this around month 6 or is there some grace period where you let patients get to steady state and then start measuring? Just be curious to know that in terms of trying to handicap the outcome here at the 6 month analysis? Thanks.
Yes. Thanks for the question. As you know, we’ve have quite a bit of experience now, Steve, in measuring this. The electronic diary has the patients enter their NRS and at certain intervals other quality of life measures daily. So, the NRS is collected daily and the baseline is defined as an average that’s taken over the run-in period. Then throughout the first 6 months, they continue to answer every day. And I can say that at least in the ENHANZE study, the compliance was very high.
So, patients are very good about entering their data. And the recall period is, what was their itch like in the past 24 hours in the last day. So, they collected daily through 6 months and the 6 month time point is the average of the last 7 days. And of course, then we have all the other data along the way, which is highly supportive, gives a kind of sensitivity analysis and really confirms that will confirm that the validity of the results collected at the end. And that was – this is the same methodology that we used in the ENHANZE study the same instrument, the same electronic device.
And then the only other thing to add there Steve is, historically in north of 100 patients in our open label Phase 2 study and the 265 patients randomized in our ENHANZE study, we’ve seen about 30% of patients have an NRS of 4 – about approximately 4 or greater at baseline. This is that moderate to severe age population pre-specified to measure this secondary endpoint. We expect to see a similar proportion in this study as well.
Awesome. Thanks so much, guys. Appreciate it.
And the next question comes from the line of Kristen Kluska with Cantor Fitzgerald. Please proceed with your question.
Hi, good afternoon. Thanks for taking my questions. So, the first, I saw that the global PBC study group is having its 10-year anniversary meeting next month. And one of the debates listed in the program was around normal ALP, which you touched on earlier in Q&A. But one of the other debates listed that caught our eye is just on whether starting a second line therapy should be conducted at 6 months or before? So, I was wondering what your thoughts on this might be, especially now that physicians might be getting closer to having another therapy if you are successful? And then anything else at this conference or event that you’re focused on given you’re very close to the data now?
Yes. Thank you for the question. Kristen, yes, we’re all very excited. Many of us will be in attendance. It’s going to be a great meeting. In terms of when should patients be treated, I think that there has historically been this somewhat arbitrary time point at one-year where you try UDCA for a year and some of the thinking was well maybe for some patients, it takes a little bit longer than others.
Increasingly, there’s been a lot of research that’s challenged and examined this. And in particular, I know that there’s been work-out of the global PBC study group that has said that even at diagnosis, if you have a level that is right around 2x upper limit at normal, there is no reason to wait, at least not wait for a full-year. And so, I know that there was a manuscript that was prepared.
I don’t know if it’s been published yet, but it really shows that the benefit versus the risk, especially for a drug like, for some of the second line therapies should be taken into consideration. The second part of your question?
Is there anything else at the conference or event that you’re keenly focused on?
Yes. So, I think you’re going to see a lot of discussion from these thought leaders who are – many of which sit on the guideline committees. So, we expect to hear a lot about different risk considerations that should influence what guidelines say and when treatment is started? And how risk is measured? So, I think alkaline phosphatase normalization as you’ve already mentioned is going to be a key consideration.
There are other risk strata that are increasingly and quite often being discussed. Higher risk bilirubin, which means bilirubin levels that are in the normal range, but at the higher end of it. So, between [0.6x and 1x] [ph] upper limit at normal is recognized as carrying greater risk for progression so patients can be low or below that 0.6x upper limit to normal, along with normal alkaline phosphatase levels, it seems that they can be put into a situation where their risk is the same as healthy subjects.
I think for us, the excitement is really the opportunity to meet with all these leaders and understand where the field is going. And I think you’re going to see a strong desire to adjust treatment guidelines. There was just a paper in alimentary pharmacology and therapeutics from the group looking at the globe score and normal alkaline phosphatase levels, recommending that normal levels should be the goal. So, this is the second important paper that’s been published that’s supporting this.
The only other thing I’d add, Kristen is, not just at this meeting for the 10-year anniversary of global, but I think increasingly in a lot of our interactions at advisory panels and throughout the course of this year, the discussion around real world data and generating real world evidence. And so, this is another area in addition to thinking about seladelpar specific impacts on disease burden, quality of life, and symptom burden for patients.
We’re committed also to thinking about the opportunities we have to generate real world data and real world evidence as seladelpar progresses potentially towards registration and commercialization if we’re successful in the program. So, these are also topics I think that we expect to have continued discussion around at this meeting and others.
Thank you for that. And with the milestone of now having over 200 patients in ASSURE, do you have an update in metric, excuse me, in terms of the number of patients that have passed 1, 2 and 3 years on drugs? Thank you again.
I’ll say this. You know ASSURE as it was set up, first brought back patients that had previously been on seladelpar. I think at least 50 of which that were potentially eligible that had been on treatment for at least 2 years from our prior clinical studies, north of 100 patients that had been on the drug for a year and then various time points even earlier from our prior ENHANZE study.
So, it’s a bit discontinuous for some of those patients as we had stopped and then restarted the program. And so by the time we started ASSURE, I think as Chuck had mentioned, there’s a good number of patients certainly with over a year of experience and even two years, particularly as you combine those two different periods for patients.
We now of course have patients rolling over from RESPONSE. So, at the time that we would expect effectively to look to file and register seladelpar, successful in response. There are many of those patients that are going to be even to the one-year time point and beyond as well, but we’ve not specifically provided numbers. I simply would tell you that when we think about the only other approved second-line treatment today, obeticholic acid, the numbers of patient exposures will have in totality, as well as those number of patients to one-year and even two-years of treatment, we believe will be even greater than the numbers that were there of obeticholic acid when it was registered.
Great. Thank you again.
And the next question comes from the line of Patrick Dolezal with LifeSci Capital. Please proceed with your question.
This is [Sebastian] [ph] on for Patrick. Just a couple from us. As it relates to pruritus, seladelpar has shown a pretty clear positive signal. Just curious if you have any evolving thoughts on the etiology of pruritus in PBC and seladelpar’s ability to modulate specific [indiscernible]. Specifically, we’ve seen data on C4 and bile acids, but have you looked at autotaxin, IL-31, or others?
Yes. Thank you for that question. It’s a great question. We have a lot of interest terms of understanding the mechanism by the effects. As you’ve mentioned, we did see correlations between baseline pruritus intensity and bile acids, as well as those patients who had a reduction in pruritus. There was also a correlation with reductions in specific bile acids. Our view at the moment is that inflammatory cholestatic disease is connected with both bile acid levels and the impact of inflammation on those.
The [indiscernible] per se have not specifically been identified, but we’re currently very active in trying to understand what the [indiscernible] might be and what the treatment effects, as seladelpar might – where the anti-pruritic effects are coming from.
Great. And just one follow-up. So, on the competitive side, it looks like Intercept is going to be submitting its post-marketing study and real world data to the FDA to fulfill post-marketing requirements. Could you just walk us through any potential implications of a full-approval for Ocaliva? Thanks so much.
Yes. I appreciate the question. So, our expectation is the same just based on their public statements. Of course, we know that their committed Phase 4 outcome study cobalt was terminated early. It didn’t show benefit. However, Intercept has obviously generated some data looking at real world evidence. It’s hard for us to really speculate what the regulators will determine.
I think one thing, if – I think specific to your question, if there is an assessment from regulators around full approval, you know at the basis of that, I would say, is a support for the endpoints themselves, the biomarker of cholestasis, namely alkaline phosphatase, and normalization of bilirubin as being somewhat validated to being tied to improvements and outcomes for patients with PBC.
And so, obviously based on what we see with seladelpar, I think that would be a strong support for what we might also see as we continue to explore the potential of seladelpar to then be tied to improvements in outcomes. These are things that we have to continue to commit to, but I think the essence of your question, if for some reason there was a full approval, I think fundamentally it supports the surrogate endpoint that we’re using in response.
The only thing I would add to that, it’s not really clear what the likelihood of that would be, but if it were to happen, I think there’s no doubt that there’s still a significant unmet need in this population. First of all, patients on obeticholic acid, don’t get to those lower levels of alkaline phosphatase, but about half of the time. And so, you would have to believe that patients getting a benefit and outcome wouldn’t be part of that subpopulation.
Obviously, there’s the issues with respect to itch. And then there’s a question of the safety and the visibility of using it in patients with compensated cirrhosis, at least those with evidence of portal hypertension. They’re currently contraindicated in the label. So, there would still be significant needs that need to be addressed and we think that seladelpar would be a potential solution for patients who have those needs.
And the next question comes from the line of Ed Arce with H.C. Wainwright. Please proceed with your question.
Great. Thanks for taking my questions and congrats on the recent deal with Kaken. Three for me. First, probably for Lewis. I appreciate all the discussion around your pre-launch infrastructure and your go to market plan. I’m wondering in particular some comments you made about patients in a market research you’ve recently done that show they prefer seladelpar’s profile over Ocaliva. Wondering if you can provide some more commentary there in particular, obviously symptomatic relief?
And then secondly, obviously, competitive PPAR compound with Phase 3 data is expected soon. Given the totality of all of the data, especially the recent data, on [indiscernible] PPAR that you reviewed in your prepared remarks, how would you view profile overall in terms of the key factors of clinical differentiation, versus that compound? And then lastly, I acknowledge this is still quite early, but in terms of pricing, my question is, how – just talk us through your thoughts here, how do you balance the need to allow for broad unencumbered patient access with the desire to capture the full clinical value, if for example, the key secondary endpoints are shown to be strongly positive? Thanks so much.
Appreciate the questions, Ed. And maybe I’ll start-off and Lewis can add on the first question here with respect to some of the work that we’ve done, very early work. It’s work that continues on today from a market research perspective and we’ll continue through the readout of response as we have confirmation, if you will, potentially of the target product profile that we believe seladelpar may have if we are successful and look to register.
When we look specifically at seladelpar versus obeticholic acid. First, I think it’s important for me to point out that anything I described to you here doesn’t come from head-to-head data, but from cross study comparisons. So, with that important caveat, what we’ve seen thus far in what we believe are similar patient populations is the ability for seladelpar to bring a greater proportion of patients to goal as it pertains to alkaline phosphatase below 1.67x the upper limit of normal and normal bilirubin whether we’re looking at 3 months or 12 months or beyond.
We also see a greater proportion of patients generally that are actually experiencing normalization, which we’ve talked quite a bit about already. And then as you mentioned, some potential favorable effects that could be, we think very significant with respect to effects on reducing pruritus symptom burden and therefore potentially improving quality of life for patients. That’s a differentiator not just from obeticholic acid, but even from first-line treatment with ursodeoxycholic acid, which has never been shown to actually reduce itch.
And then finally, just thinking about overall safety. Now, we continue to evaluate safety. It’s necessary for us to continue to do that through our development program and beyond, but the potential to have good safety across population of disease, non-cirrhotic patients, as well as compensated cirrhotic patients is also a potential differentiator. And so, this is really the overall profile put in front of HCPs, even payers when we think about some of the market research that we’ve done that have highlighted some of this potential preference for an agent like seladelpar again if we’re successful through development and gaining registration.
So, I think there’s a number of areas of differentiation efficacy, tolerability, as well as potentially safety that we think positions seladelpar quite well.
I think the only thing I would add to Sujal’s comments would be really some of the market research we’ve done with the payers and being able to really describe the target product profile and to really see their response with respect to the value proposition. And I think it’s very, very clear they see a preference to seladelpar to obeticholic acid, but more importantly, I think we got really good insights around how they really see the pricing process and really that, you know this would certainly be at par at least to current pricing that we see for obeticholic acid. But more importantly, I think is the patient co-pays are going to, I think be much more supportive of them gaining access to medicine.
And I think more importantly, certainly seladelpar’s product profile, combining that with in what we’ll see as we head into 2024, 2025 on both the commercial and the Medicare eligible side really provides a great opportunity to have less headwinds for patients to gain access to the medicine.
And then, Ed, you asked also a question around differentiation, I think relative to Elafibranor, which is in a Phase 3 study for patients with PBC, as well currently. A couple of things to highlight here. As we’ve talked already about our program as being quite robust, over a thousand patients screened in our clinical studies, our expectation by the time we would look to potentially register seladelpar would be to have north of 600 unique patient exposures. So, we’re quite confident in the profile of seladelpar to date.
We look to response to really confirm the profile that we’ve seen in a significant proportion of patients to date, all based on the things that I’ve already described. Elafibranor is a mixed PPAR alpha delta in Phase 3 for PBC, a Phase 2 study that enrolled 45 patients out to 12-weeks of treatment. 15 patients at the 80 milligram dose that they’re studying in their Phase 3 trial. So, a very relatively limited data set versus what we’ve generated for seladelpar to date.
What we’ve seen at least even in that data set is comparable alkaline phosphatase lowering, but we think there’s certainly a potential for seladelpar to differentiate on its anti-inflammatory effects, potentially differentiate on its anti-pruritic effects, as well as potentially safety. I think those three things very hard to generate any, sort of a conclusion based on the small Phase 2 study conducted with Elafibranor to date.
We’ll have to look to their Phase 3 study in order to make a better comparison of those. But we certainly believe that seladelpar is uniquely situated as a potent selective PPAR delta agonist, a mechanism that may very well carry significant advantages versus the mixed PPAR alpha delta of Genfit’s elafibranor.
Great. That’s very helpful. Thank you so much.
And the next question comes from the line of Jay Olson with Oppenheimer. Please proceed with your question.
Hi, thanks for taking the question. Congrats on the deal with Kaken. Can you please describe the market opportunity for seladelpar in Japan in terms of the patient numbers and reimbursement dynamics? And then if you could please also talk about the search criteria you used to identify Kaken as an ideal partner? And then lastly, do you have any plans to pursue other ex-U.S. partnerships besides Japan? Thank you.
Thanks for the questions Jay. I’m going to start with second part of your first question and then turn it to Lewis to talk specifically about patient numbers in Japan and the potential opportunity there. And then I’ll come back and end it with how we’re thinking about other geographic licensing opportunities. First of all, in terms of our search criteria, we’re looking for a number of things.
First of all, partner that shares in our enthusiasm around the potential for seladelpar to really accelerate patient care in PBC. Again, on the heels of, all of the specific characteristics we’ve been talking about today, having a partner obviously with experience in commercializing in specific geographies, in this case Japan, and really a history of advancing care for patients and being focused on quality of life for patients.
I think these are some of the core things that Kaken represents. And as I mentioned, we couldn’t have found a better partner that shares our enthusiasm for this opportunity. And in Japan, a country in which there are no second line treatment alternatives, we believe Kaken again as we do believes that there is a significant opportunity clearly here for seladelpar.
So, making sure we have the right partner with the right experience and the right enthusiasm is one. And then of course, a partner that’s aligned with how we think about the potential economic benefits of seladelpar. Obviously things like patient access are critically important to us. The differentiation that seladelpar may offer patients in other geographies as well.
It’s quite important and how those things tie to economics that then allow us to redistribute some of the capital. In this case, non-dilutive capital that we can continue to put forth into the program globally is the other key part of the consideration. So, we are excited to have a number of parties that conducted diligence, a number of parties I would tell you that checked the box on some of these areas.
And in the end, Kaken was really the best-in-class as it pertains to all of the areas that we’ve looked for. In terms of the overall market opportunity in Japan, I think this is an area that, in particular, Kaken is continuing to invest. I think very appropriate for them to continue to do some work here. And I think they will continue as our partner to really be able to establish how that market opportunity may present itself in Japan.
Certainly, I think Lewis can speak to just the overall prevalence numbers perhaps. And then again, I’ll come back and talk more specifically about other ex-U.S. strategies.
Thanks, Sujal. So there are about 30,000 to 35,000 PBC patients in Japan. One of the unique things about Japan is, it’s actually designated PBC as an intractable disease. And that really creates an opportunity for much better co-pays for the patients, they have a very full throated approach at allowing patients irrespective of income to have ability to get the drug and have access to the medicine.
We would anticipate somewhere between [indiscernible] patients that would be second-line opportunity, but there just still needs to be a great deal of work done on this. And I know Kaken is going to be doing some of that work.
And then finally, Jay, I know you asked about how we think about other geographies. And it’s always been our objective to bring seladelpar to patients globally. We’re committed obviously to bring seladelpar to patients in the U.S. We continue to explore those opportunities outside the U.S. RESPONSE is a study that we believe will allow us to register both in the U.S. and in Europe. And I think I’d simply tell you today, given the balance sheet, given the resources inside the company, we’re not really in an urgency.
We continue to have dialogue, but we’ll get on the other side of data, most likely and think about the right partner and the right level of economics to maximize those things really as we think about global opportunity for seladelpar with other potential partners.
Okay, great. Thank you. Look forward to that.
And the next question comes from the line of Julian Harrison with BTIG. Please proceed with your question.
Hi. Thank you for taking my questions. And apologies, I got on a few minutes late. So, hopefully, this is not already discussed. But I’m wondering if you could comment specifically on how significant you expect pruritus to be as a motivating factor for a second-line PBC patients to possibly try other treatment options when others become available?
And then PBC is clearly [front center] [ph] for now, but I’m curious if there’s anything in the primary [sclerosis and cholangitis] [ph] space that [you wouldn’t have] [ph] been before pursuing development of seladelpar more formally in that additional indication? Thanks.
Thanks for the questions, Julian. We think pruritus is critically important. First of all, it’s a direct impact on the quality of life for patients and we’ve done a significant amount of work with patient advocacy groups spending a significant amount of time in front of patients. The literature suggests as many as 70% of patients will experience pruritus in the course of their disease and again in our clinical studies, which we think is quite reflective of potentially quite reflective of the broader population, at least 30% in our trials have had moderate to severe itch.
It’s the type of itch that really never goes away even with scratching. Cholestatic itch is quite different than dermatologic itch as patients describe it affecting their ability to work, affecting their ability to be in public. So, there are some very significant elements to itch beyond this simply being plaguing, but having a broader impact overall on quality of life for patients.
And so, we think having the potential ability to reduce itch again is a critical factor. It clearly also ties to the potential for patients to stay on treatment and have significant compliance. The intention with the drug potentially like seladelpar is to reduce cholestatic markers of disease, inflammatory markers of disease, key elements that we think are related to disease progression.
And when you can have a drug that can potentially also reduce pruritus, it suggests potentially better compliance long-term that could have a significant impact on overall liver health for patients. So, these things are all tied together and at the fundamental element of it, we think pruritus is going to be a key potential differentiator for seladelpar.
Yes, the only other thing I would add is that in rare diseases and the successful marketing really hinges in many ways on activation of patients. And so the ability to be able, if confirmed in our studies and ends up in the label, the ability to communicate that directly to patients to get them activated, to have an opportunity to be aware that finally, there could be a treatment available to deal with this symptom. I think it’s going to be important part of our marketing strategy.
And then, Julian, the second part of your question, I think was geared towards potential other therapeutic areas of development for seladelpar and you mentioned specifically PSC. That’s certainly an indication we’ve thought quite a bit about and have talked a bit about in the past as well. Based on what we see with seladelpar in terms of its actions on cholestasis inflammation, the known effects we saw on reducing fibrosis and NASH patients, a mechanism in addition to these effects on pruritus that we’ve just talked about a mechanism for which we think there could very well be significant opportunity in PSC.
Today, we’re clearly focused on a near term objective to create very near term value in PBC. And I think as we continue to have discussions internally and with thought leaders, at some point if we progress forward in PSC, we’ll have more detail to share there as it pertains to endpoints and study design, but today we’re continuing to be very focused.
Okay, great. Thanks.
And the next question comes from the line of Thomas Smith with SVB Securities. Please proceed with your question.
Hi, everyone. This is Mike on for Tom. Thanks for taking our questions. On the back of the Kaken deal, can you talk about what steps from a clinical development standpoint will be needed in order for seladelpar to get to market there? And how quickly you think that could happen? And then separately, do you plan to provide numerical values on some of the secondary endpoints and specifically [to write it] [ph] as part of the initial data in 3Q? Thanks.
Well, thanks for those questions. With respect to Kaken, we’re off to a very good start. We formed execution sub teams. We’re collaborating. The tech transfer process is ongoing. In terms of the overall clinical development plan, of course, it’s Kaken’s responsibility. I will say, because it’s known that in Japan, typically, you’ll have to establish what the exposure is in Japanese subjects. And then we typically bridge to a global Phase 3 study using an efficacy study in Japanese patients.
In terms of the timing, I think it’s a little bit early for us, [we’re] [ph], as I’ve mentioned, just currently engaged with the joint steering committee, as well as these execution sub teams. But we’re really encouraged. Things are off to a really good start. We have really strong relationships. They’ve put very large team onto this. They’re really going through the data with a fine [tooth comb] [ph]. They’re asking lots of questions. We’re able to enable them with the specific information, they’re asking about potential next steps.
It just leaves us all with a very encouraging set of circumstances that we found a partner that really wants to work together to take advantage of our knowledge of the drug and the disease and their knowledge of the Japanese pharmaceutical landscape, the development and the regulatory consideration. So, I think it’s going well. As we move forward, perhaps we’ll get greater clarity on the timelines, but we’re not in a position to share those right now.
And then I know the second question was around top line data expectations. Our expectation is to share both the primary endpoint and the two key secondary endpoints that top line data readout, obviously at that point will have more of an overall safety summary as well. But it is certainly our intention to share alkaline phosphatase normalization, as well as the effect on itch in the patients with moderate to severe itch at baseline, the two key secondary endpoints in the study.
Got it. Thanks very much.
And our next question is from the line of Mayank Mamtani with B. Riley. Please proceed with your question.
Hey, team. This is [indiscernible], asking a couple of questions for Mayank. Thanks for taking them. Just to start-off, but I think this is touched on briefly, but could you give us a little bit more of your thoughts around how you’re thinking about your outcome study both from a design and timeline perspective knowing that we might see a full approval [indiscernible] by one of your peers?
Yes. Happy to take that question. Of course, we’re seeking an accelerated approval based upon surrogate that are reasonably likely to predict outcome of Subpart H approval pathway as you know and we have a post approval commitment to document outcomes. We’ve been engaged for quite some time even back in the enhanced study days in thinking through the various approaches that we might use.
We’ve had extensive set of interactions with the FDA. We’ve shared study documents. We’ve got their feedback. We’ve adjusted that. We’ve generally gained alignment on what we’ll need to document in terms of conducting a clinical outcome study. We’re not yet ready to share that quite yet for a number of considerations, but we would expect as we get close we’ll be – you’ll be learning from us all the specifics around study design, duration, number of patients, what it’s going to look like, how long we think it’s going to take.
Okay, great. Thank you. And then maybe for Sujal, if you could just talk about how you’re thinking about, I guess, the session planned from the CMO side of things as we get closer to the readout. And as you’re thinking things like post-marketing requirements?
Yes, it’s a great question. Look, I think a few important things to point out. With respect to our team internally, we don’t believe we have any gaps as it pertains to executive leadership in the clinical function. Obviously, Chuck, in the end of last year, expanded role from our Chief Scientific Officer to our President of both research and development has really been our internal de facto clinical expert ever since we launched into PBC in 2015. And so, his depth of knowledge and obviously relationship with HCPs across the globe and PBC have really been I think a cornerstone for us, and a foundation for us inside the company.
We’ve also assembled, I would tell you, just great execution leads in operations, clinical operations, clinical development, medical affairs, and biometrics. A team of individuals that have built a team below them to really execute and don’t believe we have any risk as we get to potential top line data in the third quarter as we look to even register seladelpar in – on the heels of potential success in the development program as well.
So, fundamentally, I’ll tell you, we don’t have any gaps. They don’t see any risk. We’ve just got a tremendous team up and down the organization across functions. Obviously, our goal is to continue to develop the team broadly, including in the CMO function over time, but I think very important for us to now find an individual that complements the team that exists here today.
And really can serve us as we think about the next iteration of the company in this transformation potentially from development stage to commercial.
Excellent. That’s really helpful. Thanks for taking our questions and looking forward to the data in the third quarter.
Absolutely. Thank you.
There are no further questions at this time and I’d like to turn the floor back over to Sujal Shah for any closing comments.
Well, thank you all once again for joining us today. As we approach top line data readout and RESPONSE in the third quarter, our activities and presence at medical meetings with healthcare providers, patient advocates, and many others that will play a key role in getting seladelpar to patients, all of these will continue to accelerate. It’s going to be an exciting and busy year ahead and we look forward to sharing updates with you along the way. Thank you.
This concludes today’s conference. You may disconnect your lines at this time. Thank you for your participation and have a great day.
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