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spk06: Good day, ladies and gentlemen, and welcome to SEMA Bay's fourth quarter and full year 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 investor section at the SEMA Bay website at www.semabay.com. And now I would like to turn the call over to Mr. Paul Quinlan, General Counsel at CIMA Bay. Thank you, Mr. Quinlan. Please proceed.
spk13: 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 Sujul Shah, Chief Executive Officer, Chuck McWhorter, President of Research and Development and Chief Scientific Officer, Louis Stewart, Chief Commercial Officer, and Dan Minold, 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 CIMA Bay'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 CIMA Bay 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. CIMA Bay 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 CIMA Bay'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 CIMA Bay, and any recording or rebroadcast is expressly prohibited without the written consent of CIMA Bay. At this time, I'd like to turn the call over to Sujal.
spk10: Thank you, Paul. Good afternoon, and thank you for joining us today. We finished 2022 with significant progress in our Phase III program for CELDELPAR 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 CeladalPAR'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 sell at LPAR, 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 three 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 Cell at LPAR for patients with PBC, organizational growth and focus necessary to bring Cell at LPAR to patients, and financial position to support value creation for all of our stakeholders. At the core of our clinical activities are two active global clinical trials, Response and Assure, that are part of one of the most robust development programs ever conducted for patients 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 ASLD 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 Celadal PAR 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 catalyst in the second half of this year. I will ask Louis Stewart, 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 Minold, our VP of Finance, who will provide an overview of our financials during the fourth quarter and full year 2022 before taking questions. Chuck?
spk02: 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 Celagapar 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 in 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 cellular parts 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 three registration study of Celad Alpar in PBC. The CIMA Bay 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 two to one to daily oral Celadal part 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 Celadalpar 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 one to three years of experience on Celadal PAR 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 Celadal PAR. We had significant presence at three major medical meetings in 2022. At the annual Digestive Disease Week held in San Diego last May, we had an oral presentation in the presidential plenary session on the impact of Celadalpart 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 examined the effect of Celadalpar on biochemical response and safety in patients with prior experience with abetacolic 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 Bernard Schnabel from the University of California San Diego. He describes studies established in the cell at LPAR acts through PPAR-Delta to suppress bile acid synthesis by upregulation of FGF21 in hepatocytes. This result explains, at least in part, its anticholestatic effect. Importantly, his research established that cell at LPAR suppression of bile acid synthesis is via an entirely different pathway than that of FXR agonists such as Ocaliba. 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 Cella del Par's ability to reverse establish fibrosis in mouse injury models, where it was found to provide greater effects than either an FXR agonist for a thyroid hormone beta receptor agonist, both of which are in active development for fibrotic liver disease. Traditionally, the flagship meeting for us is the liver meeting hosted by the American Association of Liver Disease. Held in November of last year in Washington, D.C., we had two new presentations of clinical results for Celadalpar and PBC. The first was a poster reporting on a post hoc clove analysis of lipids from the Celadalpar Open Label Phase II and Phase III enhanced studies in PBC. Dyslipidemia is a common feature in PBC, and so we were interested in understanding how lipids were affected by Celadalpar treatment in PBC patients. Changes in lipids were analyzed for 373 patients with PBC receiving daily oral treatment, placebo, 5 mg or 10 mg Celadalpar 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. Celadalpar treatment resulted in dose-dependent decreases in total cholesterol and LDL cholesterol. and these changes were significant for those taking Celadopar 10 mg 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 Celadopar seen thus far is encouraging in this aspect. A second clinical presentation was made by the SEMA Bay research team describing an analysis of the serum metabolome of 160 patients completing three months of treatment in the enhanced study. This analysis found broad dose-dependent changes in the unbiased survey of 1,474 metabolites. Speladelpar was found to increase serum markers of mitochondrial, and paroxysomal fatty acid beta oxidation, indicated by increases in carnitine and acyl carnitines, and decreases in dicarboxylates, and significantly reduced serum levels of inflammatory lipid mediators, including long-chain fatty acids, mono and diacylglycerols, eicosanoids, ceramides, and sphingomyelins. Measured in our target PBC population, These results provide clinical evidence of Celadopar'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 II 52-week dose-ranging study of Celadopar in adult patients with PBC receiving Celadopar as add-on therapy to first-line ursodioxycholic acid or as monotherapy, that the patients intolerant to UDCA were published. The first paper, published in the Journal of Hepatology with the lead author, Professor Chris Bolas, describes the treatment response on patients enrolled with a minimum serum alkaline phosphatase level of 1.67 times the upper limit of normal, or 194 units per liter. And these patients were on average in excess of 318 units per liter. Celadalpar 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 and 10 milligrams were 53% and 67%. The 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 in Liver International last year reporting the effects of Celadopar treatment in the 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 and 10 milligram cohorts, respectively. After one year, patients reporting improvement substantially outnumbered those who worsened in the total 5D itch scale and PBC40 itch and fatigue domain questionnaires. Improvement in sleep disturbance at one year was reported in 81% of the 5mg cohort and 78% of the 10mg cohort in those patients with baseline itch-related sleep disturbance by the 5D itch score, with similar results using the PBC40 sleep questionnaire. Cell-at-all part-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 III placebo-controlled enhanced study, which we have now submitted for publication. Finally, I want to recognize our medical affairs team as we increase our effort to broaden engagement and scientific exchange with PBC key opinion leaders, our other healthcare providers, and advocacy groups. Sujal?
spk10: Thank you, Chuck. We made great strides supporting our overall goal to bring Cell at LPAR 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 Celadal PAR 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 Celadelpar 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 Selladelpar in Japan for PBC, SEMA-Bay received an upfront payment of $34.2 million and will receive potential milestone payments totaling up to 17 billion yen, approximately $128.4 million at current exchange rates for the achievement of certain regulatory and sales milestones, in addition to 20-plus percent net effective royalties. Kaken will be responsible for development, regulatory approval, and commercialization of Celadelpar 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 Celadelpar 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 Celadalpar in our ongoing clinical studies and to supply CELADELPAR 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 Louis Stewart, our Chief Commercial Officer, to outline key initiatives in this area.
spk16: Louis? Thank you, Sujal. In 2022, our commercial focus was on assessing Philadelphia's global market opportunity while conducting foundational market research and analysis within prioritized 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 CellaDelpar'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 CelaDelPAR. 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. CBA'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 for their PBC patients. Our success in achieving this vision begins with the science of Celadilpar 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 three clinical study results from Enhance gives us confidence in Celadelpar's promise of becoming an optimal solution for changing the future PVC 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 Cellidelpar's success will be maximizing patient access and compliance. Our U.S. market access landscape research reveals payer's preference for Cellidelpar's target product profile over that of a betacolic acid. Other analysis indicates consistent coverage of OCA in recent years, reflecting our confidence in CellaDelPAR 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 costs, including in many cases, the elimination of monthly copays. Our development of a high touch service model will be designed to support each patient's access to CellaDelPAR, as well as their overall treatment experience. A third strategic theme of our go-to-market plans will be to maximize Sela del Par value in the U.S. while leveraging local expertise through partnerships in ex-U.S. prioritized regions. The recent announcement of our collaboration with 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.
spk01: Dan? Thank you, Louis. 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 continued to advance other required clinical and regulatory activities necessary to complete our late-stage development of Celadelpar and PBC. And finally, we made further progress in manufacturing, as well as in medical affairs and commercial, where we continued to plan and prepare for a potential future launch of Celadelpar and 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 31st, 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 I NDA-enabling clinical studies. Research and development expenses for the years ended December 2022 and 2021 were $68 million and $64.5 million, respectively. Overall, these expenses were higher in 2022 due to a $5.6 million increase 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 Celadelpar and PVC, 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 30 cents and 34 cents 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 Sella Del Par and PBC. Let me now hand the call back to Sujal.
spk10: Thank you, Dan. We could not be more excited about the year ahead of us at SEMA-B. 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 SEMA Bay to bring our Phase III 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 Celadalpar'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 SEMA Bay for all of our stakeholders, most importantly patients. We're now happy to take questions. Operator?
spk06: Thank you, sir. We will now be conducting a question and answer session. If you would like to ask a question, please press star 1 on your telephone keypad. A confirmation tone will indicate that your line is in the question queue. You may press star two if you would like to remove your question from the queue. For participants using speaker equipment, it may be necessary to pick up your handset before pressing the star keys. One moment, please, while we poll for questions. And our first question comes from the line of Yasmine Rahimi with Piper Sandler. Please proceed.
spk08: Good afternoon, team, and congrats on all the great progress, and we're really looking forward to the data. A few questions for you. One of the feedbacks we have been getting as we speak with PBC doctors is how the entire PBC community is moving forward towards alkaline normalization rather than one times six, seven, the upper limit. So I would love to ask the question with that, 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 one. Bucket two is, so Joel, I'm certain that strategic interest has 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 recognize that that really helped expedite the enrollment, but could you maybe put in context how those measures reduced heterogeneity and maybe ensured 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.
spk10: Thank you for the questions, Yaz. 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 the 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 Celadalpar, where in our clinical studies to date, we've seen anywhere from 30 to 40 percent of patients enrolled in our prior studies between one and two years of treatment actually experience normalization of alkaline phosphatase. There's no question that there's a push now to think about treating patients really to normal biochemistries. It's not something that HCPs, 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 Selladelpar has. Chuck, anything to add? No, I think that's a pretty good summary. So I think the other part of your question, then the second part of it, Yaz, is around the pros and cons around M&A. You know, first, let me be clear. We're really building SEMA Bay 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 Celadalpar 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 CELADELPAR to as many patients that may benefit is 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 interests, 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. You know, 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 Celadalpar 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 CELDELPAR 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.
spk03: Yeah, and just to get to your question, Yaz, about, you know, the outcome or the benefit that we saw in terms of the outreach that we made. You know, we sent team members across North America, Europe, Middle East, even to Asia for these site visits. We held the investigator meetings. The impact of that, yes, to the enrollment, but also it's about relationships. 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, 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 the clinical sites in our study. I think for a rare disease, this is really, really important.
spk08: Thank you so much for all the great color.
spk06: And the next question comes from the line of Steven Seedhouse with Raymond James. Please proceed with your question.
spk15: Great. Thanks for taking the question. You know, it seems to us that in addition to the primary endpoint, there's, you know, some secondary effects to the drug, including on pruritus, of course, where you could really differentiate teledelpar from other competitors on the market potentially. So I had a couple 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, you know, the PBC40 scoring system. Are you measuring these as secondary endpoints? Do you have any expectations for demonstrating improvement on those? Same question basically for liver function tests, ALT and AST. This is something you'll quantitatively look to show benefit on in response.
spk10: Yeah, thank you for the question, Steve. Maybe, Chuck, you want to give some commentary?
spk03: Yeah, so I think it's a very good observation, Steve. Appreciate that. As you may know from our Liver International paper, which was an open-label study, we did show improvements in those measures in the PBC40, the sleep disturbance domain, as well as in the 5DH sleep measures as well. And then on fatigue, in that study, that was a paper diary-driven assessment. In HANCE and now in response, we're also measuring those as well, that's the answer to your question. But we're using an 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 Selladel part to see if we can see a consistent pattern. We'll just have to wait and see.
spk10: The only other thing I'd add to that, Steve, is, you know, from a broad perspective with respect to the program overall, even as we approach top-line data and response, we're very focused in continuing to understand these effects in PBC patients even beyond the Phase III study. So, of course, measuring puritis, collecting PBC40, and understanding the potential effects of Celadalpar on fatigue and sleep disturbance, and even looking at the effects of Celadalpar on liver enzymes, including ALT in particular, You know, 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 Celadalpar for patients with PBC, anything that we learn through this additional work, we would look to share at medical meetings and eventually publish as we have done historically.
spk15: That's great. I just want to ask about the paritis endpoint as well, obviously, given how important that is. And, you know, 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 four criteria. And then – This is measured, I believe, as a weekly average at a six-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 zero to month six, or is this around month six, 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 six-month analysis. Okay.
spk03: Yeah, thanks for the question. As you know, we 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 six months, they continue to answer every day. And I can say that at least in the enhanced study, the compliance was very high. So patients are very good about entering their data. And the recall period is, you know, what was their itch like in the past 24 hours in the last day. So they collected daily through six months. And the six-month time point is the average of the last seven 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 the validity of the results collected at the end. And this is the same methodology that we used in the enhanced study, the same instrument, the same electronic device.
spk10: And then the only other thing to add there, Steve, is historically, in north of 100 patients in our open-label phase two study and the 265 patients randomized in our enhanced study. We've seen about 30% of patients have an NRS of four, about approximately four 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.
spk15: Awesome. Thanks so much, guys. Appreciate it. Yeah. Thank you.
spk06: And the next question comes from the line of Kristen Kluska with Cantor Fitzgerald. Please proceed with your question.
spk09: 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 six 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?
spk03: Yeah, thank you for the question, Kristen. Yeah, we're all very excited. Many of us will be in attendance. It's going to be a great meeting. You know, in terms of when should patients be treated, I think that there is – 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 it's right around two times upper limit and normal, there's 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 some of the second-line therapies, should be taken into consideration. The second part of your question?
spk09: Is there anything else at the conference or event that you're keenly focused on?
spk03: Yeah, so I think you're going to see a lot of discussion from these thought leaders, 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 0.6 and one times upper limit of normal. is recognized as carrying greater risk for progression. If patients can be lower below that 0.6 times upper limit of 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 that's, 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.
spk10: 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 is the discussion around real-world data and generating real-world evidence. And so this is another area, in addition to thinking about cell at LPAR-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 CELADELPAR 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.
spk09: Thank you for that. And with the milestone of now having over 200 patients in Assure, do you have an updated metric, excuse me, in terms of the number of patients that have passed one, two, and three years on drugs? Thank you again.
spk10: I'll say this. You know, Assure, as it was set up, you know, first brought back patients that had previously been on Celadelpar and I think at least 50 of which that were potentially eligible that had been on treatment for at least two 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 enhanced 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 Celadal PAR if 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, you know, the only other approved second-line treatment today, abetacolic acid, the numbers of patient exposures we'll 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 for abetacolic acid when it was registered.
spk09: Great, thank you again.
spk05: Thank you.
spk06: And the next question comes from the line of Patrick Dolezal with LifeSci Capital. Please proceed with your question.
spk11: This is Sebastian on for Patrick. Just a couple from us. As it relates to pruritus, cell delpar has shown a pretty clear positive signal. Just curious if you have any evolving thoughts on the etiology of pruritus in PBC and CellDelPAR's ability to modulate specific pruritogens. Specifically, we've seen data on C4 and bile acids, but have you looked at autotaxin, IL-31, or others?
spk03: Yeah, thank you for that question. It's a great question. We have a lot of interest in 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 pruritogens per se have not specifically been identified, but we're currently very active in trying to understand what the pruritogens might be and what the treatment effects of celadalpar might, where the antipuritic effects are coming from.
spk05: Great, and just one follow-up.
spk11: 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 OCALDA? Thanks so much.
spk10: Yeah, I appreciate the question. So our expectation is the same just based on their public statements. Of course, we know that their committed phase four outcome study, COBOL, was terminated early and 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, 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, you know, a support for the endpoints themselves, the biomarkers 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 Cell at LPAR, I think that would be a strong support for what we might also see as we continue to explore the potential of Cell at LPAR to then be tied to improvements and 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.
spk03: The only thing I would add to that, you know, 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 abeticolic acid, you know, 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 on an outcome wouldn't be part of that subpopulation. Obviously, there's the issues with respect to itch, and then there's the 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 Solidel part would be
spk05: a potential solution for patients who have those needs.
spk06: And the next question comes from the line of Ed Ars with HC Wainwright. Please proceed with your question.
spk14: Great. Thanks for taking my questions. And congrats on the recent deal with Cochrane. Three for me. First, probably for Louis. 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 showed they prefer Celadalpar's profile over Ocaliva. Wondering if you can provide some more commentary there, in particular, obviously, symptomatic relief. And then secondly, excuse me, obviously competitive PPAR compounds with phase three data is expected soon. Given the totality of all of the data, especially the recent data on celled LPAR that you reviewed in your prepared remarks, how do you view the 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, 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.
spk10: I appreciate the questions, Ed. And maybe I'll start off, and Louis can add on the first question here with respect to you know, some of the work that we've done, very early work. It's work that continues on today from a market research perspective and will continue through the readout of response as we have, you know, confirmation, if you will, potentially of the target product profile that we believe Cellidelpar may have if we are successful and look to register. When we look specifically at Cellidelpar versus abetacolic acid, first, I think it's important for me to point out that anything I describe 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 Celadalpar to bring a greater proportion of patients to goal as it pertains to alkaline phosphatase below 1.67 times your upper limit of normal and normal bilirubin, whether we're looking at three 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, you know, we think very significant with respect to effects on reducing puritis, symptom burden, and therefore potentially improving quality of life for patients. That's a differentiator not just from abetacolic 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 a population of disease, non-cirrhotic patients as well as compensated cirrhotic patients is also a potential differentiator. And so this is, you know, 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 Celadalpar, again, if we're successful through development and gaining registration. So, you know, I think there's a number of areas of differentiation, efficacy, tolerability, as well as potentially safety that we think positions Celadel Park quite well.
spk16: I think the only thing I would add to Sujil'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 sell a Delparte to a betacolic acid. But more importantly, I think we got really good insights around how they really see the pricing process and, and really that, you know, this would certainly be at par at least to current pricing that we see for betacolic acid. But more importantly, I think is that patient co-pays are going to, I think be much more, um, supportive of them gaining access to medicine. And I think more importantly, certainly Celadelpar's product profile compiled with that, combining that with what we'll see as we head into 24-25 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.
spk10: And then, Ed, you asked also a question around differentiation, I think, relative to Elifibrinor, which is in a Phase III study for patients with PBC as well currently. A couple of things to highlight here. You know, as we've talked already about our program as being quite robust, over 1,000 patients screened in our clinical studies. Our expectation by the time we would look to potentially register Celadalpar would be to have north of 600 unique patient exposures. So we're quite confident in the profile of Celadalpar to date. You know, 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. Elifribinor is a mixed PPAR alpha delta in phase three for PBC, a phase two 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 three trial. So a very relatively limited data set versus what we've generated for Celadalpar 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 Celadalpar to differentiate on its anti-inflammatory effects, potentially differentiate on its antipyretic 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 two study conducted with Elifibrinor to date. We'll have to look to their phase three study in order to make a better comparison of those. But we certainly believe that Celadelpar 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 genfits-elafibrinor.
spk14: Great.
spk06: 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. Oh, hey.
spk07: Thanks for taking the question. Congrats on the deal with Kakin. 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 the ideal partner. And then lastly, do you have any plans to pursue other ex-U.S. partnerships besides Japan? Thank you.
spk10: Thanks for the questions, Jay. I'm going to start with the second part of your first question and then turn it to Louis 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, a partner that shares in our enthusiasm around the potential for Cell at LPAR 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 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's a significant opportunity clearly here for Celadalpar. 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 Cell and LPAR. Obviously, things like patient access are critically important to us. The differentiation that CellDelPAR may offer patients in other geographies as well is 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're excited to have a number of parties that conducted diligence, a number of parties I would tell you that 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. You know, in terms of the overall market opportunity in Japan, you know, I think this is an area that in particular Kaken is continuing to invest in. 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 Louis 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.
spk16: Thanks, Sujil. 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, you know, ability to get the drug and have access to the medicine. We would anticipate somewhere between 7,000 and 7,500 patients that would be a second-line opportunity. But there still needs to be a great deal of work done on this, and I know Kakan's going to be doing some of that work.
spk10: And then finally, Jay, I know you asked about how we think about other geographies, and it's always been our objective to bring CeladalPAR to patients globally. We're committed obviously to bring Celadel part of 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 sell at LPAR with other potential partners.
spk07: Okay, great. Thank you. Look forward to that.
spk05: Thank you.
spk06: And the next question comes from the line of Julian Harrison with BTIG. Please proceed with your question.
spk17: Hi. Thank you for taking my questions. And apologies, I got on a few minutes late, so hopefully this was 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 second-line TBC patients to possibly try other treatment options when others become available. And then PVC is clearly front and center for now, but I'm curious if there's anything in the primaries, sclerosing, cholangitis space that you're waiting to happen before pursuing development of CellDelPAR more formally in that additional indication. Thanks.
spk10: Thanks for the questions, Julian. You know, we think puritis 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 puritis in the course of their disease. And again, in our clinical studies, which we think is quite reflective of a, potentially quite reflective of the broader population, at least 30% in our trials have had moderate to severe itch. You know, 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, you know, affecting their ability to work, affecting their ability to be in public. So there are some very significant elements to itch you know, beyond this simply being plaguing, but having, you know, a broader impact overall on quality of life for patients. And so we think having the potential ability to reduce it, again, is a critical factor. It clearly also ties to the potential for patients to stay on treatment and have significant compliance. You know, the intention with a drug potentially like Celadalpar is to reduce colostatic 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 puritis, 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 puritis is going to be a key potential differentiator for cell at LPAR.
spk03: Yeah, the only other thing I would add is that in rare diseases, 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 the symptom I think is going to be an important part of our marketing strategy.
spk10: And then, Julian, the second part of your question I think was geared towards potential other therapeutic areas of development for Cell at LPAR, and you mentioned specifically PSC. You know, 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 Celadalpar in terms of its actions on cholestasis, inflammation, the known effects we saw on reducing fibrosis in NASH patients, a mechanism in addition to these effects on puritis 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.
spk17: Okay, great. Thanks very much.
spk06: And the next question comes from the line of Thomas Smith with SVB Securities. Please proceed with your question.
spk12: Hi, everyone. This is Mike on for Tom. Thanks for taking our question. On the back of the Kalkin deal, can you talk about what steps from a clinical development standpoint will be needed in order for CellaDelPAR 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 Purita as part of the initial data in 3Q. Thanks.
spk03: Yeah, well, thanks for those questions. And, you know, 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, you know, 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 you would typically bridge to a global phase three 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, 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 a very large team onto this. They're really going through the data with a fine-tooth comb. They're asking lots of questions. We're able to enable them with specific information. They're asking about potential next steps. It just leaves us all with a very encouraging a set of circumstances that we've 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 considerations. 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.
spk10: And then I know the second question was around top-line data expectations. You know, our expectation is to share both the primary endpoint and the two key secondary endpoints at top-line data readout. Obviously, at that point, we'll 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.
spk05: Got it. Thanks very much.
spk06: And our next question is from the line of Mayank Mamthani with B. Riley. Please proceed with your question.
spk04: Hey, team. This is Donald Casme asking a couple questions for Mayank. Thanks for taking them. Just to start off with, I think this was 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 package be submitted this year by one of your peers?
spk05: Yeah, happy to take that question.
spk03: Of course, we're seeking an accelerated approval based upon surrogates that are reasonably likely to predict outcome with 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 an 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 our 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, 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.
spk05: Okay, great. Thank you.
spk04: And then maybe for Sujil, if you could just talk about how you're thinking about, I guess, the session plan from the CMO side of things as we get closer to the readout and as you're thinking about things like post-marketing requirements.
spk10: Yeah, 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, you know, his depth of knowledge and obviously relationship with HCPs across the the globe in 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 cell at LPAR on the heels of potential success in the development program as well. So, you know, fundamentally, I'll tell you, we don't have any gaps. I 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.
spk04: Excellent. That's really helpful. Thanks for taking our questions and looking forward to the data in the third quarter.
spk06: Absolutely. Thank you. There are no further questions at this time. And I'd like to turn the floor back over to Sujil Shah for any closing comments.
spk10: 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 CeladelPAR 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.
spk06: 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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