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spk09: Good day, ladies and gentlemen, and welcome to the SEMA Bay's first quarter 2022 financial results and business update conference call. At this time, all participants are in a listen-only mode. Following the formal remarks, we will open the call up 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. Now I'd like to turn the call over to Mr. Paul Quinlan, General Counsel at CIMA Bay. Mr. Quinlan, please proceed.
spk10: Thank you, operator, and good afternoon, everyone. I hope that you've had a chance to review the press release we issued announcing our first quarter 2022 financial results and business update. You can access that release on our website under the Investors tab. Joining me on the call today are Sujal Shah, Chief Executive 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 trial enrollment dates, cash runway and planning for commercialization are forward-looking statements as defined under the Private Securities Litigation Reform Act of 1995. Although the company believes that the expectations reflected in such forward-looking statements are based upon reasonable assumptions, actual outcomes and results are subject to risks and uncertainties and could differ materially from those forecast due to the impact of many factors. The company assumes no obligation to update or supplement any forward-looking statements, whether as a result of new information, future events, or otherwise, except as required by applicable law. Participants are directed to the cautionary statements set forth in today's press release, as well as the risk factors set forth in CIMA-based quarterly and annual reports filed with the SEC for factors that could cause actual results to differ materially from those anticipated in the forward-looking statements. This conference call is the property of SEMA Bay, and any recording or rebroadcast is expressly prohibited without the written consent of SEMA Bay. At this time, I'd like to turn the call over to Sujal.
spk13: Thank you, Paul. Good afternoon and thank you for joining us today. As it is less than two months since our 2021 year-end call, our updates today will be brief as we turn our attention in the second half of this year to key milestones in our unwavering journey to bring Celadelpar to patients with primary biliary cholangitis, or PBC. Our phase three development program for Cell at LPAR in PBC includes ongoing NDA-enabling PK studies, ASURE, a long-term safety study to complete a comprehensive patient safety database, and RESPONSE, our second phase three efficacy and safety study to support marketing approval. We believe this program is the most extensive program for any investigational drug currently in development for the treatment of PBC. These clinical studies draw from the extensive experience we gained from our prior phase two and phase three development, where data have continued to support the potential for Celadalpar to address many of the unmet needs faced by patients with PBC. Results we previously shared from our 52-week open-label Phase II study in over 100 PBC patients dosed with Celadalpar were published last month in the Journal of Hepatology. The opportunity to have these data featured in one of the world's preeminent medical journals for liver diseases elevates Celadalpar's visibility as a differentiated drug candidate for patients with PBC. We continue to believe Celadelpar has the potential to address three important unmet needs for patients with PBC. First, many patients need therapies with improved activity against the disease, as exhibited in the incomplete responses commonly observed in their liver lab tests for cholestasis and liver injury. These tests include levels of alkaline phosphatase, bilirubin, and transaminases, biomarkers that have been associated with histological progression and poor outcomes for patients with PBC. We believe that offering patients an improved biochemical response and especially the opportunity to achieve biochemical normalization should be the aspiration of therapy in PBC. Second, many patients with PBC suffer from significant burden of symptoms, including puritis. Currently approved therapies have not addressed this need, and the only approved second-line treatment, abetacolic acid, has been associated with new onset or exacerbation of puritis. A therapy that can provide symptom relief would improve patients' lives, potentially improving acceptability and adherence to therapy. Lastly, PBC patients encompass a spectrum of disease stage ranging from those without cirrhosis to those with compensated cirrhosis, including with portal hypertension. A leading treatment option should be safe across this spectrum of non-cirrhotic and compensated cirrhotic stages of disease. These data, along with data from our prior Phase III enhanced study that we have presented at past medical meetings, continue to excite and motivate investigators and their patients to participate in our ongoing clinical studies. Central to our clinical development program for Cell at LPAR and PBC is response. Our second global Phase III registration study targeted to enroll 180 PBC patients who have had an inadequate response to or are intolerant to first-line treatment, ursodeoxycholic acid. Since our last call, we have made steady progress toward completing enrollment. However, the COVID-19 pandemic continued to have an impact on screening and enrollment at clinical sites globally. A cycle of implementing then easing restrictions as variants emerged and subsided and lingering resource issues at clinical sites have been primary factors affecting our projected timeline for response. Timelines for enrollment have also been affected by our suspension of activities in Ukraine and halting of further enrollment in Russia. Our efforts to mitigate the delay have included increased in-person visits with investigators at their sites, additional investigator meetings for US, Latin American, and European investigators, implementation of patient referral initiatives, and activation of additional sites. This has resulted in consistent progress over the past few months, despite ongoing global challenges. We now have over 150 sites activated across 26 countries. As we approach what we project to be the final month of screening, we have greater visibility into monthly metrics and now forecast completion of enrollment occurring in the third quarter. We remain confident in our ability to execute given our extensive clinical and operational experience with Celldell PAR development in PBC globally. Importantly, we continue to expand the clinical experience with Celadelpar in the Assure long-term open-label study. We have now begun to roll over patients completing response into Assure. Together with patients that entered into Assure from prior studies with Celadelpar, there are approximately 140 patients in this study taking Celadalpar daily. This level of investment underscores our commitment to collect data on the long-term safety and durability of efficacy of Celadalpar. We believe this is fundamental to our success in seeking approval and eventually in marketing Celadalpar. In addition to fueling our ongoing clinical efforts, Our prior experience has provided us rich data sets that have been featured at major medical meetings since we began development of CellDelPAR for patients with PBC in 2015. Through the remainder of this year, we are excited about multiple opportunities to feature data and analyses at upcoming GI and hepatology congresses. In two weeks, Celadalpar will be featured in three abstracts presented at the annual Digestive Disease Week held in San Diego from May 21st to the 24th. The first is an oral presentation in the Presidential Plenary Session by Professor Bettina Hansen from the University of Toronto. The presentation, entitled Celadalpar Treatment of Patients with Primary Biliary Cholingitis for two years improves the GLOBE PBC score and predicts improved transplant-free survival, supports that long-term treatment with Celadalpar was associated with improved prognosis, and supports an emerging view regarding the promise of earlier intervention in disease. Two additional oral poster presentations will also be made. The first by Dr. Stuart Gordon, Professor of Medicine at Wayne State University and Director of the Division of Hepatology and GI Research at the Henry Ford Health System, describes a pooled analysis of phase two and three data on the efficacy and safety of Celadalpar in PBC patients with compensated liver cirrhosis. The second presentation by Dr. Aliya Ghulam Hussain assistant professor at the University of Toronto Center for Liver Disease, describes an analysis of the efficacy and safety of Celadalpar in PBC patients who have had prior treatment with abetacolic acid or fibrase. We look forward to these presentations and further engagement with many of the key experts supporting our ongoing work with Celadalpar in PBC. Before I ask Dan to review our first quarter financials, let me provide a brief update on our second clinical program. Last year, AdventHealth initiated patient dosing of MBX2982 in a two-period crossover pharmacology study using a hypoglycemic clamp technique to evaluate the levels of counterregulatory glucagon release under conditions of low blood sugar. MBX2982 is a GPR119 agonist discovered and developed by CIMA Bay. It has completed five previous clinical studies, including in subjects with prediabetes and type 2 diabetes. The product concept being investigated for MBX2982 in the current study is as an agent to potentially prevent or minimize hypoglycemia in patients with type 1 diabetes. The study is being conducted by AdventHealth Translational Research Institute in Orlando, Florida, and is fully funded by the Leona M. and Harry B. Helmsley Charitable Trust. SEMA Bay retains all rights to MBX 2982. In addition to safety and tolerability, the primary endpoints are maximal glucagon release and glucagon area under the curve for MBX 2982 versus placebo treatment periods. These results will guide our decision on whether to pursue further development for hypoglycemia associated with diabetes. This 28-day study is targeted to enroll up to 29 participants. We are projecting to have these data prior to year end if recent progress in enrollment continues in the coming months. Turning our attention to financial results for the first quarter, we have remained diligent with managing our expenses and focusing our activities where we have near-term opportunities to create significant value. The current market environment has been as challenging as we have seen in our industry over several years. The capital we raised last year gives us a balance sheet that allows us to advance our global clinical activities for CELADELPAR and report top line data from response in 2023. We believe we are well positioned to weather the pressures of the global markets, as well as those facing the biotech industry today. Before taking questions, I'll ask Dan to review our first quarter financials. Dan?
spk04: Thank you, Sujal. As Sujal has highlighted, in the first quarter of 2022, we continued to make additional progress on our PBC development plan objectives. In clinical development, We made advances in our ongoing efforts to enroll and treat PBC patients and to conduct other required clinical activities in our response, assure, and other NDA-enabling clinical studies that are necessary to complete our late-stage development of Celadalpar and PBC. We also made additional progress in manufacturing development, as well as in medical affairs and commercial, where we began early-stage efforts to plan for a potential future launch of Celadalpar and PBC. Overall, our cash, cash equivalents and investments totaled $193.4 million as of March 31st, 2022, and included $25 million of third tranche funding received from Abingworth in the first quarter of 2022. We believe this cash on hand together with additional committed capital available to us under the Abingworth Financing Agreement is sufficient to fund our current operating plan through 2023. I will now turn to a brief review of our first quarter operating results. Net loss for the quarter ended March 31st, 2022 was $27.8 million or 32 cents per share compared to a net loss of $17.6 million or 25 cents per share in the quarter ended March 31st, 2021. Net loss was higher in the quarter ended March 31st, 2022 compared to the corresponding period in 2021 largely due to an increase in clinical trial activities associated with the ongoing late-stage development of Celladelp RMPVC, as well as an increase in accretion of interest expense related to the Abingworth Development Financing Arrangement. In particular, operating cost increases were primarily driven by an expansion of our site activation, patient enrollment, and other clinical trial activities associated with Response and Assure, our two active global late-stage clinical trials in PBC, and higher employee compensation associated with the hiring of additional personnel to support the PBC development plan. We expect our operating expenses to increase in the future as we continue to execute on our clinical development, manufacturing, and commercial readiness plans for PBC. Let me now hand the call back to Sujal.
spk13: Thank you, Dan. It has been a long road towards bringing Selladelpar back to patients with PBC, and we are as committed as we have ever been to seeing the process through to completion. Our teams have worked tirelessly against the backdrop of a global pandemic and a market environment that has put pressure on our entire industry. Our focus has been on managing the things we can control. which we believe has positioned us well to create significant value for patients and our stakeholders. In recent months, we have seen strategic interest in PBC that we believe underscores the significant unmet needs facing patients today. We believe Celadelpar has the potential to advance care for PBC patients in a way that is differentiated relative to very few options that exist today. Belladelpar is now one of the only late stage opportunities in this area that remains fully unencumbered. As we look to close out enrollment in response in Q3, we expect to have multiple opportunities to highlight important data sets at upcoming medical meetings throughout this year. We also plan to host an investor day before year end to highlight our vision for positioning CeladalPAR to advance the care of PBC patients around the world. We're now happy to take questions. Operator?
spk09: Thank you. 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 your line is in the question queue. You may press star 2 if you'd like to remove your question from the queue. Four participants using speaker equipment may be necessary to pick up your handset before pressing the start keys. One moment, please, while we poll for your questions. Our first question comes from the line of Yasmeen Rahimi with Piper Sandler. Please proceed with your question.
spk06: Hi, this is Emma on for Yaz. Thank you for taking our questions. We have three for you. First, could you kindly provide us some commentary on how confident you are about finishing response enrollment by 3Q22? What percent of total patients are fully enrolled at this junction? Second, we are certain you are getting M&A interest on partnering Salel Depart in PBC. Could you walk us through at what junction you think it is most appropriate to pull the trigger? And third, congrats on securing three DDW presentations, including the presidential plenary session. Could you please kindly tell us if there are any new aspects of the Salel Depart data that you will be presenting that we've not yet seen and the significance of this new data set? Thank you.
spk13: Appreciate the questions, Emma. I'll answer the first two, and I'll ask Chuck to provide some additional context on the presentations at DDW. So, you know, I think as most folks know, as I mentioned in the remarks, you know, we've been 100% focused on advancing Celadal PAR for patients with PBC, and over the last year have done everything in our control effectively to deal with the pressures that we've faced relative to the pandemic. And and additional competition for patients. As mentioned, one of the biggest challenges has been, you know, the waxing and waning of restrictions in various geographies at different periods in time. Now, the positive is over the last few months, we've now started seeing very steady and consistent progress. So, it gives us a greater ability to now predict the completion of enrollment than we had previously over the last year. I'll remind you that first patient randomized in response occurred in April of last year, so we're a little over 12 months from the first patient coming into the study. It's not atypical as we reach a crescendo in the number of sites activated and as broad of a program as we have in response across 26 countries around the world, you know, to start to see an increase in that enrollment, and what's not atypical absent some of the challenges presented by the pandemic is to start seeing a meaningful acceleration as you get to a critical mass of number of sites. I think that's one of the things that's been different with the backdrop of the pandemic, harder to see consistent acceleration. But as I mentioned, we've started to see several months of very consistent, steady enrollment. That gives us the ability now to project towards the completion of enrollment. Now, these are projections But again, this is an indication in which we have been experiencing development of Celadal PAR since 2015, strong relationships with sites globally. We've done this before. We've fully enrolled a prior phase three study. So we're quite confident in execution and how we need to do what we need to do over the course of the coming months. with this greater visibility to the timeline really comes this vision and view around completing enrollment in the third quarter. We don't tend, Emma, to provide any percentage around enrollment. But again, I think I would take the comments just given where we are in this study and a view towards what's necessary to complete enrollment really as a guide towards the confidence that we have in executing and completing enrollment in the third quarter. Much greater visibility today than we had even several months ago. Now, you talked a little bit about M&A and partnering interest in this space as well. Obviously, in the last six months, we've seen two separate transactions in the PBC space. And as I mentioned, again, in the prepared remarks, CELA Delpar, we believe, is really one of the only fully unencumbered late-stage assets in PBC. Now, our development program, as extensive as it has been, and the program inclusive of both Assure and Response, we believe will provide us with the opportunity to register CeladalPAR, not just in the U.S., but also in Europe. And so we certainly have the balance sheet and the wherewithal to execute through completion of the program, but it's the principle of ours to always evaluate strategic interest as an alternative to ultimately putting CeladalPAR in the hands of as many PBC patients globally as we possibly can. And I think we are sitting in a very strong position ultimately to capitalize on the meaningful amount of interest we've seen in the space, the highly differentiated and de-risk profile of Celadalpar and PBC to ultimately execute on a strategic plan that creates the greatest value. And as I mentioned, put Celadalpar on the hands of as many patients globally as possible. So those types of discussions remain ongoing. And I would simply say that, you know, we're very excited, frankly, about the opportunities to partner potentially to really bring Celadelpar to patients globally. We certainly, again, have it within our vision to bring Celadelpar to patients throughout the U.S., but this is an important global strategy for us, so we'll continue to evaluate ongoing discussions with various parties.
spk06: Thank you. Thank you very much. And the last one about the DDW presentations, could you kindly tell us if there's any new aspects of the soil-to-par data that you'll be presenting that we may not have seen yet and the significance of the new data set?
spk01: Yeah, Emma, this is Chuck. I'd be happy to take that question. Yeah, we were very, very excited to get selected for the presidential plenary section. And what we're presenting here, I do have to respect the embargo for DDW, so there's limitations in what I can tell you, but I do hope I can pique your interest to really go see something that I think is going to be quite interesting. This, we're using the GLOBE score, which is a validated prognostic risk tool, but basically comprised of five factors, age, alkaline phosphatase levels, bilirubin levels, platelet count, and albumin. And all of those are factors that are known to be related to risk of progression. And this continuous score system is now being used to not just identify the risk for progression, but to look at treatment response. And so the story in the presentation is that the data suggests, the GLOBE score changes suggest that there's been an improvement in event-free survival in those patients treated for two years with Celadelpar. And so what's different here? Why is this important? Well, the GLOBE score is a continuous variable, and it's basically an online tool that's available. The physician can type in the patient's numbers and get a prediction for risk. It's different than it's used for regulatory approval, which has also been validated, in the sense that it makes more scientific sense. If you have a patient whose alkaline phosphatase level is close to the regulatory threshold of 1.67 and they change by a very small amount, it doesn't make sense that there's really been that much of a change in the risk. On the other hand, the GLOBE score, being a continuous variable, if you get a large change but they're not below that 1.67, you've really established that they've had an improvement in their outlook and their outcomes. And so we believe that while we'll continue to anchor on the regulatory endpoint for approval, we think the GLOBE score, this continuous score system, will likely become part of medical practice, and it may be incorporated into future clinical research. So I think we're really paving the way there. And I think if you're able to attend the session, for those in the audience that can, I think you're going to see some analysis that looked at different aspects of the patient population and give us some real insights into where Celadelpar might be directed once it hopefully gets to the market.
spk06: Thank you very much.
spk09: Thank you. Our next question comes from the line of Steven Seedhouse with Raymond James. Please proceed with your question.
spk03: Good afternoon. Thank you for taking the question. Sujal, you are speaking More about sort of strategic interest and how you're thinking about that than I've heard you in the past. And it's pretty interesting given what we just saw with Ocala, the ex-U.S. rights basically being sold somewhere between 400 and 500 million, depending on milestones coming through. So I wanted to ask just with that peg in the ground, what do you think of that price? And how are you thinking about the ex-U.S. value and opportunity and best way to capitalize on that for CIMA Bay?
spk13: I appreciate the question, Stephen. You know, I think as we continue to progress with our own development, we're certainly anchored by our ability to carry forward and complete the development program for CELADELPAR, not just in the U.S., but for registration, as I mentioned, even in Europe. But clearly, as we do more work, and we'll look forward in the second half of this year, as mentioned, to share a bit more of the market research and commercial strategy that we're putting together to prepare ourselves upon potential success for Celadel, part of the development program. But we're really excited about opportunities we see, A, to deliver a solution, if you will, to patients that meet a significant number of consistent unmet needs today, as well as an opportunity to really expand the addressable patient population. I think some of what we've seen With other transactions, you mentioned the sale of the rights to betacolic acid outside the U.S. for a little over $400 million to Advans Pharma, I think really underscores what we believe to be an opportunity, again, to expand addressable patient population here specifically in that transaction outside the U.S. You know, this is something that we believe is absolutely an opportunity for Cell at LPAR to really capitalize on. And so as we've progressed, you know, it's always been an important priority for us to evaluate a host of different strategic alternatives. And so I'd simply say that, you know, the fact that we've talked a bit more about it really positions us in a position to think about, you know, as I said, capitalizing on the right alternatives for us as we move forward.
spk03: All right, I appreciate that. A couple of sort of more housekeeping questions. I wanted to ask, because I noticed the inclusion-exclusion criteria entry for response on clintrials.gov was expanded a little bit on March 21st, I would say, but it just looked like it was adding more details to clarify what was already there. So I wanted to ask if there's been any material changes to inclusion-exclusion criteria in that study. And then second, I want to know if you expect data for MBX2982 in first half of this year and if that sort of reporting of data is actually in your hands or in your partner admin. Thanks.
spk13: Yeah, happy to answer those two questions. You know, I think not atypical in a global protocol-like response to see some amendments throughout the conduct of the study. I think the most significant of which recently has come out of some of the work we've done in renally impaired patients You know, this lowered the GFR threshold for exclusion criteria for patients. That obviously makes it easier for some patients to enroll into the study because we didn't see as much of an effect in that study from Celadalpar. So that was a positive and, again, opens up the opportunity for some patients that come across that threshold to enroll into the study. There's also a shorter period for washout for those patients that have been on prior treatment, specifically abetacolic acid and or fibrates historically. And so again, that just helps us at least offer up an opportunity for patients to come into the study more quickly, again, if they're eligible to enroll. So I think those were probably the two most significant that we believe certainly have helped us and will continue to help us completing enrollment in response. With respect to MBX 2982, you know, here again, we've seen some positive trends recently in enrollment in that Phase 2A study. You mentioned correctly the study is being run by AdventHealth and fully funded outside of SEMA Bay, but we retain the full rights to the program. We certainly will be involved with those groups in actually sharing and publicizing the data, so you should expect to see that come from you know all the parties involved inclusive of sema bay and we're really excited about the potential for that study to complete enrollment in the coming months so that in fact we can be in a position to share that data before year end thanks i appreciate all the detail thank you thank you our next question comes from the line of patrick dolezal with lifestyle capital please proceed with your question
spk05: Hi, thanks for taking the questions. I guess on the topic of business development, I'm curious how you're thinking about pipeline expansion, if at all. And if so, would there be a focus on earlier stage assets or would you ever consider a more transformative transaction, you know, such as a merger kind of with a later stage company in a similar space perhaps? And then the second question is just really on pre-commercial pre-commercialization preparations, whether you've engaged the physician community or payers, and kind of what the response has been thus far, if so.
spk13: Yeah, Patrick, I appreciate the questions. You know, look, I think we're grounded first and foremost by near-term opportunity to create value for patients, of course, for our shareholders as well. And so the center of that is execution on Celadalpar. And so we're unwavering in our level of focus in completing enrollment and response, executing on the global clinical program that's inclusive of Assure, a study that we think adds to our phase three development program and our prior history of development to really position Celadalpar as really being the most extensive program in PBC in development today. That's where we're grounded because we know as de-risked and differentiated as the profile for Celadalpar is today, that the greatest amount of value in the near term will be created off of us really executing well on that program. So that's first and foremost our priority. There's no question that as we think about future opportunities to create value, we've certainly built teams here at SEMA Bay with extensive experience from research to clinical operations and clinical development, regulatory, quality, CMC. And as we add that final leg, if we're successful with Celadal PAR around commercial, We certainly believe we have the infrastructure internally and expertise to capitalize on additional opportunities. You talked a little bit about opportunities in similar spaces. Of course, there's a depth of experience here inside the company around inflammation and fibrosis. Tremendous amount of focus, obviously, here today, near term in liver and GI. But we certainly could envision ourselves opening up and expanding to other differentiated opportunities. I think they'd have to fit well. with our areas of focus and internal expertise. And it'd have to be the right timing and the right opportunity. So again, I wouldn't take away our focus from CELADELPAR and the near-term opportunity to create value. But certainly as we think beyond that, we believe we're well positioned to continue to feed pipeline and growth opportunities longer term. That's absolutely an inherent thought process of ours as we continue to progress. You know, with respect to just the inputs that we've had from a pre-commercial perspective, you know, we've started to do a fair bit of market research. We've talked to physicians. Obviously, we've been closely involved with experts in the PBC community globally for many years. But we've continued to gather these data at internal advisory meetings. We've gathered a fair bit of market research data. That continues today, Steve. I'd say we've been seeing a tremendous response, and much of it is anchored, again, on the significant amount of data that we've collected to date. You know, data demonstrating anticholestatic benefits of Celadalpar, anti-inflammatory benefits of Celadalpar, as well, importantly, as effects on improving, you know, key clinical symptoms of disease, including fatigue, as well as, importantly, pruritus. That profile, I think, is at the center of the positive response that we see from The medical community, the payer community will continue to do that work. And ultimately, the final data set, should it really support the profile we've seen with the drug thus far? As I'll mention, in north of 300 PBC patients that we've dosed with Celadalpart to date, many of which have actually gone even out to two years of treatment, we're excited about this opportunity from a commercial perspective. And again, I think you'll see us share a lot more of that insight as we complete enrollment in the third quarter and we get to the later part of this year.
spk05: Thanks, you Joel. Appreciate it. Thank you Patrick.
spk09: Thank you. Our next question comes from the line of Ed Arcee with HC Wainwright. Please proceed with your question.
spk02: Hi everyone. Thanks for taking my questions and congrats on the progress with enrollment in the face of multiple challenges here lately. Four questions for me, if I may. Firstly, on enrollment of response, could you tell us how many patients have been enrolled? Now that you're looking at less than 30 additional to get to full enrollment, we see an acceleration the end to some degree of over-enrollment, and is that something you'd actually be interested in? Secondly, with regards to the ASURE study, the long-term open-label study, I think you said there were 140 patients now rolling over from response. Just wanted to confirm that. And more broadly, as it's part of the NDA filings, and you're looking at, I think, a total of 500 patients in that study, submit the data that's available at the time of filing. Thirdly, I wanted to ask about the initial efficacy and response that you're looking at from MDX 2982. And specifically, the maximum glupigon release and the area under the curve that you mentioned, and any sort of benchmarks that you're looking for, either qualitatively or quantitatively. And then lastly, for Dan, the fourth question is just on the financials looking throughout this year, is it reasonable to expect that while we would see steady increases in R&D through the year, the GNA should be relatively flat. And thank you for answering my questions.
spk13: Absolutely, Ed. I think I've got all that here written down. If I missed anything, you can catch me up here. You know, first of all, with respect to enrollment and response, we've not indicated specifically the number of patients that are randomized into the study. I think you mentioned a number of less than 30 If I read that correctly or heard that correctly, what we did mention is that we've got 150 sites activated, so not specifically patients randomized, but 150 sites across 26 countries around the world. I'd simply tell you this, you know, projecting enrollment timelines, you know, is always a bit tricky and always carries some risk. And I think that challenge is no more so than today, given the backdrop of the pandemic, as we've talked about on prior quarterly calls, as well as today. Where we sit today is at a point in time where now we have at least a consistent level of data over the last three or four months. If all we do is maintain that consistent level of enrollment, then we project the study to be enrolled in Q3. Clearly, internally, our objective is to try to accelerate enrollment. We've talked a little bit about the fact that one of the key activities over the last two months has been for various members of our team to be face-to-face at investigator sites. We've actually been face-to-face with almost 80% of our SQS European investigators. We've been largely across North America, Latin America, Europe, and APAC well over a majority of sites that we visited ourselves at SEMA Bay, not just our CRO, but SEMA Bay representatives. There's no question that that level of engagement takes commitment, but clearly we think will generate results. So we're actively involved with every site, actively working through the needs of sites to try to get this study enrolled as quickly as possible. And all of our initiatives are anchored around trying to accelerate that level of enrollment. But we're certainly, as I mentioned, quite positive around what we've seen recently over the last few months. And again, if we just maintain that consistent level of enrollment that we've seen the last three months going forward, we do expect this study to complete enrollment in the third quarter. Now, you also asked a bit about Assure, where we do have about 140 patients now on the Assure long-term study. a study that, again, just gives us a tremendous amount of data, both safety as well as long-term efficacy of Celadalpar. Importantly, the first sets of patients completing response, I mentioned the first patient into the study was April of last year, so clearly we're beyond the 52-week treatment period. And I'm happy to say that we've already started rolling over those first sets of patients that came into response into Assure. The vast majority of that 140, however, are patients that have been in prior clinical studies, either our Phase II open-label study or our prior Phase III enhanced study. That's where much of that population comes from. You also mentioned the number 500. I'm not sure quite what that refers to. We don't expect to see that many patients from Assure. Again, we had north of 300 patients that had been dosed with Celadalpar even as we started response. We're excited to see almost half of those already come into the Assure study. I think ultimately beyond response and Assure, We do have a commitment because approval in PBC occurs from an accelerated subpart H approval pathway to commit to a long-term outcome study. Again, we're in the final stages of agreement with regulators around what we think will be a very novel approach to that outcome study relative to what we've seen historically in PBC. And so we'll have more to share on that as that process is finalized, and as we, again, complete enrollment and eventually complete the response phase three clinical study, but that's yet to come, and we're completing that dialogue with the agency as we speak. Your third question, I think, was really around initial efficacy and response around expectations with MBX2982 in the proof of pharmacology study. And, you know, here I'll, again, ask Chuck to jump in and give you some context around this study.
spk01: Yeah. Hi, Ed. So I think the basic design that we used was, you know, a good one in the sense that we are also including healthy subjects. So the healthy subjects will give us a good benchmark for what, you know, what we expect from the mechanism in terms of its ability to elaborate glucagon. And, of course, then that is related to its ability to restore normal glucose levels from the low blood glucose levels that we induce with the hyperinsulinemic clamp.
spk13: And then I'll ask Dan to answer the questions around financials through the rest of this year.
spk04: Sure, yeah. Thanks for the question. You know, without a doubt, as you noted, we will be focused on executing the development, the R&D, Our investments there are unwavering. We'll be spending for the completion of Response and Assure and other NDA enabling studies. With respect to G&A, it will be largely flat throughout the year. We really want to be thoughtful through this time of completing our enrollment and really thinking through that and the trajectory ultimately towards data. you know, watching our costs as we move forward.
spk02: Thanks for taking my questions, guys. Appreciate it. Thanks, Ed. Thanks.
spk09: Thank you. Our next question comes from the line of Jay Olson with Oppenheimer & Company. Please proceed with your question.
spk08: I'd like to follow up one on the response study and the other probably on the M&A front. So for the response study, I just want to confirm we have more colors on. Is your projection to complete the enrollment in 3Q based on your currently active 150 sites where you need to run or you need to open additional sites at a pace that we've seen in the past few months? And on the M&A, I'm just wondering what's your view on US and S-US PVC markets Do you see that as like separate opportunities or it's like one package? And also, if you can comment on whether the cash runway protection also include the investment in building the commercial infrastructure and also pre-launch preparation. Thank you.
spk13: Yeah, thank you for the question. So, you know, with respect to response, we do, as I mentioned, expect to complete enrollment in Q3. I think you asked whether or not that's predicated on additional sites. Certainly, we believe that the sites that are activated today can allow us to accomplish the completion of enrollment based, again, on where we are today and what we project into the future. You know, that's one of the things that we actually have at our disposal as well. to mitigate some of the challenges of the pandemic. And so you may very well see even additional sites than what are currently represented on clinicaltrials.gov, you know, once again to ensure that we hit these timelines. But I think fundamentally where we are with our plan, we're confident that the plan will allow us to execute to complete enrollment here in the near term. With respect to M&A U.S. versus ex-U.S., I think we ultimately look at geographies, you know, somewhat independently. The goal within CIMA Bay is clearly to get Celadal PAR to patients globally that can benefit. That includes the U.S., it includes Europe, it includes geographies outside of those jurisdictions, Asia, Latin America. And so I think ultimately we're going to develop a plan and continue to execute on a plan that is likely to involve partners, particularly in geographies outside of where we're based today. You know, clearly the most significant opportunity is in the U.S. alone. There our strategy is to execute and ultimately build our opportunity to commercialize and bring Celadal part to patients on our own. We can certainly do that in regions outside the U.S., but we recognize the challenge that exists there from an infrastructure perspective. And so once again, we're actively involved even today and will continue to be in thinking about potential strategic partnerships that can allow us to do that effectively in a cost-effective manner and still create significant value, obviously, for all of our stakeholders. And then finally, you asked a little bit about cash runway. You know, the cash runway we've provided to date, in fact, doesn't include a commercial launch. So, ultimately, we're expecting our cash to last through the end of next year. Clearly, upon successful top-line data, we believe there's opportunities for us to continue to execute and fund the next stage of development to create value around a variety of different alternatives. Again, we look at financing strategy long-term as being inclusive of potential partnership strategy and various non-dilutive sources of capital, as well as a host of other vehicles that we've deployed in the past as well. You know, we feel as though we have quite a few levers to pull as we continue to move forward, but current guidance around cash running through the end of next year is not predicated upon ultimately post-NDA filing approval and launch. We certainly would look to file the NDA as quickly as possible post-topline data. All of that, of course, is already embedded in our projections.
spk08: Great. Thanks for the callers.
spk09: Thank you. Our next question comes from the line of Kristin Kluska with Cantor Fitzgerald. Please proceed with your question.
spk11: Hi, everyone. This is Rick on for Kristin. Thank you for taking our question. We've just got one here. In a paper that we recently saw published in Frontiers in Immunology, researchers looked at the role of hepatic CD8 T cells in a mouse model of PBC, identifying two distinct subsets of T cells with high cytokine production. and greater proliferation potential, respectively. Given the potential role for celadelpar in inflammation and fibrosis, how are you thinking about its potential role in interacting with resident immune cells in the liver and how that could be associated with PBC pathogenesis? Thank you.
spk13: Thank you for that question. I'll ask Chuck to give some comments here. Chuck?
spk01: Yeah, I just want to make sure I was off of mute. So thank you for that question. And I think, you know, that is a, that publication that you cited is one of a number that have looked at with increasing interest in the roles of various immune cells, whether they be T cells or NK cells and the like in autoimmune liver diseases. The short answer to your question is we're intrigued by it, but we haven't yet developed any data that really indicates to us that we've established one way or another whether it is or is not a role. We did do a study that we presented in abstract at a recent meeting where we looked at its effect in an immune-mediated fibrosis model where we saw that Celadalpart did decrease both liver and renal fibrosis. So that may be one indication that there may be something there. But it's the question of liver immunology is one that's currently continuing to advance. And I think that's something that we'll just have to understand going forward. But it is an area that is interesting.
spk11: Okay. Thank you very much.
spk09: Thank you. Our next question comes from the line of Mayank Mamthani with B. Reilly Securities. Please proceed with your question.
spk07: Hi, this is Yuan An for Mayank. Thank you for taking our questions. Since you are now close or near enrollment completion, do you have a sense of what portion of the patients have biopsy taken?
spk13: Yeah, thank you for that question. So, of course, in a blinded fashion, we are able to see how many patients have in fact, volunteered for biopsy. I think we talked a little bit in the past around the fact that biopsy in this study is still voluntary for patients. They're not required to have a baseline and then a 52-week paired liver biopsy. We're, of course, encouraging patients to do so. We're required to share a subset of those with the agency. And so it is a number we're able to track. And once again, we're confident in our ability to deliver on what our agreement has been with the agency. We've talked a little bit about the fact that in the past, In our enhanced phase three study, about 16% of patients actually volunteered for that baseline biopsy, and our agreement with the agency is something that we think is certainly something we can accomplish in the context of response as well.
spk07: Got it. Thank you for the additional comment. And one more question from us. Can you remind us how your regulatory path in EU might be different than those in U.S.? ? And what about other territories, and how might that inform your BD transactions you might be evaluating right now?
spk13: Yeah, it's a good question. You know, we certainly believe, based on what we've seen historically in the setting of PBC and precedents, as well as guidelines in Europe, as well as the U.S., that response, we believe, will allow us to register sell at LPAR both in the U.S. and in Europe. So from a regulatory perspective, Again, we believe that the primary endpoint in response will allow us to register in both geographies. I think when you think a little bit about other territories, again, the data set we think is supportive. The endpoints we think are supportive. Clearly, there are some geographies, Japan as an example, where you have to have at least, you know, some sets of data to demonstrate PK and potential in that population. So there could be additional work clearly in geographies like Japan and China as well. So there's some specifics, you know, outside of just U.S. and Europe. But fundamentally, we think this data set from response will really support registration in a host of geographies outside the U.S.
spk07: Thank you for the additional comment. That'll be all. Thank you.
spk09: Thank you. Our final question comes from the line of Thomas Smith with SBB Securities. Please proceed with your question.
spk12: Hi, everyone. This is Mike on for Tom. Thanks for taking our question. Sujal, you talked a little bit about expanding the addressable population in PBC. Just looking at the U.S. market, it seems like sales have started to slow down pretty meaningfully. Do you think that this is a market that should see pretty meaningful growth from now until the time that you get to market?
spk13: You know, it's a great question. And, you know, you talked a little bit about sales starting to plateau, and I presume you're referring to betacolic acid. When we think about Celadelpar, we think there are a number of key opportunities. First of all, in those patients who are clearly incomplete responders to first-line treatment with ursodeoxycholic acid, there's a need for greater efficacy in not just in reducing cholestasis and inflammation, but really starting to normalize biochemical response in patients. So that's one thing. We think Celadalpar is quite differentiated from even abetacolic acid when you look at separate, of course, separate data sets, not head-to-head data. But we think that alone demonstrates an opportunity for us to have significant growth opportunity just in second-line treatment. We think the tolerability is another key element of that. When we think about persistency and adherence to treatment alternatives, We know that abetacolic acid can potentially cause or worsen puritis in patients with PBC. And so when we look at some of the data sets with abetacolic acid, clearly that impacts their opportunity in the market. And we think Celadalpar can be quite differentiated, have a greater level of adherence. And we talk a bit about just tolerability, but clearly actually having a potential benefit on puritis and reducing itch I think patients would argue is actually an efficacy outcome for them. And so those are some of the core elements of the cell at LPAR profile, along potentially with safety. You know, we've seen a couple of label revisions for betacolic acid, particularly in more advanced populations. We've shared some data sets in compensated cirrhotics with and even with portal hypertension and without portal hypertension. And so there's much more work for us to do here. But clearly here, once again, an opportunity to treat the spectrum of disease and the spectrum of the population, you know, we think is yet a third potential differentiator that would support a much more growing opportunity, say, for Cellidelper in just the second-line treatment setting. I think with that profile, certainly we have a tremendous amount of excitement and confidence around potentially expanding market opportunity There's a tremendous amount of data being generated now around the benefit of treating patients earlier with treatments that get them fully to biochemical normalization. So again, patients that might otherwise wait for second-line treatment, opportunities to treat them earlier and improve potential outcomes for patients, we think these are some of the things that can lead to overall expansion of the addressable patient population. So we're excited to continue to explore that. and to continue to see where our data sets would potentially support that growth.
spk12: Got it. That's very helpful. Thanks. Thank you.
spk09: Thank you. Our next question is a follow-up from Mayank Mamtani with B. Reilly Securities. Please proceed with your question.
spk07: Thank you. One more question from us. It seems like one of your peers might have Phase 3 data slightly ahead of you guys. So we are wondering, how are you anticipating that to shape the narrative for what the expectation should be for response? And do we know if they will have more severe patients included? Thank you.
spk13: I appreciate the question. So I presume you're referring to the ongoing development of Elifibinor in patients with PBC, where we did hear the sponsor refer to completing screening last month. You know, our projection is with a run-in period that usually goes beyond screening, that that study could potentially enroll here in the coming weeks, if not towards the end of this month. You know, I think fundamentally we're focused on what we can control. Obviously, we're putting every effort to getting response enrolled as quickly as possible. But I will importantly say that, you know, in addition to just response, the Assure data set we think gives us a tremendous amount of, you know, potential data supporting not just efficacy but also safety in this population. We think this program will still yet be much more extensive than even the development program for Elifibranor in the setting of PBC. These are some of the things that I think will be quite important as we ultimately see the data sets from these two programs currently in phase three. We've also had the benefit of effectively targeting a number of patients and powering response, not just for the primary and key secondary endpoint around biochemical response and normalization of biochemical response, but also around treating puritis. That's something that we think we're advantaged around given our prior data set. So, you know, I think at the end of the day, our push is to get the study enrolled as quickly as we can. but it's also to have the most extensive, expansive quality data set, and we think the latter is something that will certainly position Celadal Park quite well against other potential treatment alternatives.
spk07: Great. Thank you for taking our questions.
spk13: Appreciate it. Thank you.
spk09: Thank you. There are no further questions at this time. I'd like to turn the conference back over to Mr. Shaw for any closing remarks.
spk13: I appreciate it. So, you know, once again, as we approach the second half of the year, we expect to provide multiple updates at major medical meetings and investor conferences through the remainder of this year. Against the backdrop of what has been a very challenging biotech market, we are grounded by the strength of our existing data and ongoing late-stage development that we believe highlight a significant opportunity for CellDelPAR and PBC. We believe we are well positioned with a strong balance sheet and a highly de-risked differentiated lead program to capitalize on creating significant value. We look forward to completing enrollment in the coming months ahead and speaking to you all once again soon.
spk09: Thank you. This concludes today's teleconference. You may disconnect your lines at this time. Thank you for your participation and have a wonderful day.
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