CymaBay Therapeutics Inc. (CBAY) Q1 2022 Earnings Call Transcript

CymaBay Therapeutics Inc. (CBAY 0.03%)
Q1 2022 Earnings Call
May 12, 2022, 4:30 p.m. ET

Contents:

• Prepared Remarks
• Questions and Answers
• Call Participants

Prepared Remarks:

Operator

Good day, ladies and gentlemen, and welcome to the CymaBay's first quarter 2022 financial results and business update conference Call. [Operator instructions] Please be advised that the call will be recorded at the company's request. It is also being webcast live on the investors section at the CymaBay website at www.cymabay.com. Now, I'd like to turn the call over to Mr.

Paul Quinlan, general counsel at CymaBay. Mr. Quinlan, please proceed.

Paul Quinlan -- General Counsel

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 Menold, VP, finance.

Following our prepared remarks, we will open the call for Q&A. Before we begin, I'd like to remind everyone that statements made during this conference call, including the Q&A session relating to CymaBay's expected future performance, business prospects, events or plans, including clinical plans, regulatory approvals, funding and repayment schedules, anticipated timelines and 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 CymaBay's quarterly and annual reports filed with the SEC for factors that could cause actual results to differ materially from those anticipated in the forward-looking statements. This conference call is the property of CymaBay, and any recording or rebroadcast is expressly prohibited without the written consent of CymaBay. At this time, I'd like to turn the call over to Sujal.

Sujal Shah -- Chief Executive Officer

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 seladelpar to patients with primary biliary cholangitis, or PBC. Our phase three development program for seladelpar in PBC includes ongoing NDA-enabling PK studies; ASSURE, 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 seladelpar to address many of the unmet needs faced by patients with PBC. Results we previously shared from our 52-week open-label phase two study in over 100 PBC patients dosed with seladelpar 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 seladelpar's visibility as a differentiated drug candidate for patients with PBC.

We continue to believe seladelpar as 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 pruritus. Currently approved therapies have not addressed this need and the only approved second-line treatment obeticholic acid has been associated with new onset or exacerbation of pruritus, 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 three ENHANCE 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 seladelpar in PBC is RESPONSE, our second global phase three 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 U.S., 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 months 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 seladelpar development in PBC globally. Importantly, we continue to expand the clinical experience with seladelpar 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 seladelpar, there are approximately 140 patients in this study taking seladelpar daily. This level of investment underscores our commitment to collect data on the long-term safety and durability of efficacy of seladelpar. We believe this is fundamental to our success in seeking approval and eventually in marketing seladelpar.

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 seladelpar 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, seladelpar will be featured in three abstracts presented at the annual Digestive Disease Week held in San Diego from May 21 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 Seladelpar Treatment of Patients with Primary Biliary Cholangitis for two years improves the GLOBE PBC score and predicts improved transplant-free survival. Supports that long-term treatment with seladelpar 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 Mr.

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 seladelpar in PBC patients with compensated liver cirrhosis. The second presentation by Dr. Elia Guam Hussain, assistant professor at the University of Toronto Center for Liver Disease, describes an analysis of the efficacy and safety of seladelpar in PBC patients who have had prior treatment with obeticholic acid or fibrates. We look forward to these presentations and further engagement with many of the key experts supporting our ongoing work with seladelpar 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 MBX-2982 in a two-period crossover pharmacology study using a hypoglycemic clamp technique to evaluate the levels of counter-regulatory glucagon release under conditions of low blood sugar. MBX-2982 is a GPR119 agonist discovered and developed by CymaBay. It has completed five previous clinical studies, including in subjects with prediabetes and type two diabetes.

The product concept being investigated for MBX-2982 in the current study is as an agent to potentially prevent or minimize hypoglycemia in patients with type one 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.

CymaBay 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 period. 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 seladelpar and report top line data from RESPONSE in 2023. We believe we are well positioned to weather the pressures of the global market, as well as those facing the biotech industry today. Before taking questions, I'll ask Dan to review our first quarter financials. Dan?

Dan Menold -- Vice President, Finance

 Thank you, Sujal. As Sujal has highlighted, in the first quarter of 2022, we continue 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 seladelpar in 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 seladelpar in PBC.

Overall, our cash, cash equivalents and investments totaled $193.4 million as of March 31, 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 31, 2022, was $27.8 million or $0.32 per share compared to a net loss of $17.6 million or $0.25 per share in the quarter ended March 31, 2021.

Net loss was higher in the quarter ended March 31, 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 seladelpar in PBC, 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, 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.

Sujal Shah -- Chief Executive Officer

Thank you, Dan. It has been a long road toward bringing seladelpar 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 seladelpar has the potential to advance care for PBC patients in a way that is differentiated relative to very few options that exist today. Seladelpar 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 seladelpar to advance the care of PBC patients around the world. We're now happy to take questions. Operator?

Questions & Answers:

Operator

[Operator instructions] Our first question comes from the line of Yasmeen Rahimi with Piper Sandler. Please proceed with your question.

Emma Nesson -- Piper Sandler -- Analyst

Hi. This is Emma on for Yas. Thanks 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 3Q '22? What percent of total patients are fully enrolled at this junction? Second, we are certain you are getting M&A interest on partnering seladelpar 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 seladelpar data that you'll be presenting that we've not yet seen and the significance of this new data set?

Sujal Shah -- Chief Executive Officer

Appreciate the question, Emma. I'll answer the first two, and I'll ask Chuck to provide some additional context on the presentations at DDW. So I think as most folks know, as I mentioned in the remarks, we've been 100% focused on advancing seladelpar for patients with PBC. And over the last year, have done everything in our control effectively to deal with the pressures that we face relative to the pandemic and additional competition for patients.

As mentioned, one of the biggest challenges has been 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 a typical 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 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 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 toward the completion of enrollment. Now, these are projections, but again, this is an indication in which we have been experiencing development of seladelpar 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 the study and a view toward what's necessary to complete enrollment really as a guide toward 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, seladelpar, 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 seladelpar, 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 seladelpar 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 derisked profile of seladelpar in PBC, to ultimately execute on a strategic plan that creates the greatest value. And as I mentioned, put seladelpar in the hands of as many patients globally as possible. So those types of discussions remain ongoing. And I would simply say that we're very excited, frankly, about the opportunities to partner potentially to really bring seladelpar to patients globally.

We certainly, again, have it within our vision to bring seladelpar 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.

Emma Nesson -- Piper Sandler -- Analyst

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 seladelpar data that you'll be presenting that we may not have seen yet and the significance of the new data set?

Chuck McWherter -- Chief Scientific Officer

Yes. This is Chuck. I'd be happy to take that question. Yes, we are 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 take your interest to really go see something that would -- I think it's going to be quite interesting. This -- we're using the GLOBE score, which is a validated prognostic risk tool that 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 that GLOBE score changes suggest, that there's been an improvement in event-free survival in those patients treated for two years with seladelpar. And so, what's different here? Why is this important? While 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 from 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 would be a continuous variable.

If you get a large change, but they're not below that 1.67, you've really establish that they've had an improvement in their outlook and their outcome. 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 seladelpar might be directed once it hopefully gets to the market.

Emma Nesson -- Piper Sandler -- Analyst

Thank you very much.

Operator

Thank you. Our next question comes from the line of Steven Seedhouse with Raymond James. Please proceed with your question.

Steven Seedhouse -- Raymond James -- Analyst

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 Ocaliva ex U.S. rights basically being sold somewhere between $400 million 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 CymaBay?

Sujal Shah -- Chief Executive Officer

Yes, I appreciate the question, Steve. And I think as we've continued to progress with our own development, we're certainly anchored by our ability to carry forward and complete the development program for seladelpar, 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 seladelpar in 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 obeticholic acid outside the U.S. for a little over $400 million to Advent 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. This is something that we believe is absolutely an opportunity for seladelpar to really capitalize on.

And so, as we've progressed, it's always been an important priority for us to evaluate a host of different strategic alternatives. And so, I'd simply say that the fact that we've talked a bit more about it really positions us in a position to think about, as I said, capitalizing on the right alternatives for us as we move forward.

Steven Seedhouse -- Raymond James -- Analyst

All right. 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.

It was expanded a little bit on March 21, 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 MBX-2982 in first half of this year? And if that sort of reporting of data is actually in your hands or in your partner Advent? Thanks.

Sujal Shah -- Chief Executive Officer

Yes. Happy to answer those two questions. 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.

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 seladelpar. 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 wash-out for those patients that have been on prior treatment, specifically obeticholic 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, here again, we've seen some positive trends recently in enrollment in that phase twoa study. You mentioned correctly the study is being run by AdventHealth and fully funded outside of CymaBay, 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 all of the parties involved, inclusive of CymaBay. 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.

Steven Seedhouse -- Raymond James -- Analyst

Thanks, Sujal. Appreciate all the detail.

Sujal Shah -- Chief Executive Officer

Thank you, Steve.

Operator

Our next question comes from the line of Patrick Dolezal with LifeSci Capital. Please proceed with your question.

Patrick Dolezal -- LifeSci Capital -- Analyst

Hi. Thanks for taking the question. 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, 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-commercialization, preparations, whether you've engaged the physician community or payers and kind of what the response has been thus far, if so?

Sujal Shah -- Chief Executive Officer

Yes, Patrick, I appreciate the question. 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 seladelpar. And so, we're unwavering in our level of focus and completing enrollment in 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 seladelpar as really being the most extensive program in PBC in development to date.

That's where we're grounded because we know as derisked and differentiated as the profile for seladelpar 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 CymaBay 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 seladelpar 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. A 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 have to be the right timing and the right opportunity. So again, I wouldn't take away our focus from seladelpar in 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. With respect to just the inputs that we've had from a pre-commercial perspective, 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.

Data demonstrating anti-cholestatic benefits of seladelpar, anti-inflammatory benefits of seladelpar as well, importantly, as effects on improving 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, we'll 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've mentioned, in north of 300 PBC patients that we've dosed with seladelpar 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.

Patrick Dolezal -- LifeSci Capital -- Analyst

Thanks, Sujal. Appreciate it.

Sujal Shah -- Chief Executive Officer

Thank you, Patrick.

Operator

Our next question comes from the line of Ed Arce with H.C. Wainwright. Please proceed with your question.

Ed Arce -- H.C. Wainwright -- Analyst

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 acceleration to the end to some degree of over enrollment. And is that something you'd actually be interested in? Secondly, with regards to the ASSURE 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 filing and you're looking at, I think, a total of 500 patients in that study, do we some 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 MBX-2982, and specifically, the maximum glucagon release and the area under the curve that you mentioned.

Any sort of benchmarks that you're looking for, either qualitatively or quantitatively? And then lastly, for Dan, the fourth question, is just the financials looking throughout this year. Is it reasonable to expect that while we would see a steady increases in R&D through the year, the G&A should be relatively flat? And thank you for answering my questions.

Sujal Shah -- Chief Executive Officer

Absolutely, Ed. I think I've got all that here written down. If I miss anything, you can catch me up here. First of all, with respect to enrollment in 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, projecting enrollment timelines is always a bit tricky and always carry 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 we 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 ex U.S. European investigators. We've been largely across North America, Latin America, Europe and APAC, well over a majority of sites that we've visited ourselves at CymaBay, not just our CRO, but CymaBay 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 in 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 seladelpar. 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 two open-label study or our prior phase three ENHANCE study. That's where much of that population comes from. You also mentioned the number of $500 million.

I'm not sure quite what that refers to. We don't expect to see that many patients from Azure. Again, we had north of 300 patients that have been dosed with seladelpar 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, had -- was really around initial efficacy and response around expectations with MBX-2982 in the proof of pharmacology study. And here, I'll again ask Chuck to jump in and give you some context around this study.

Chuck McWherter -- Chief Scientific Officer

Yeah. Hi, Ed. So I think the basic design that we used was 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 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 levels that we induced with the hyperinsulinemic clamp.

Sujal Shah -- Chief Executive Officer

And then I'll ask Dan to answer the questions around financials through the rest of this year.

Dan Menold -- Vice President, Finance

Sure. Yes. Thanks for the question. 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 toward ultimately toward data.

So we're going to be very watching our costs as we move forward.

Ed Arce -- H.C. Wainwright -- Analyst

Thanks for taking my questions, guys. Appreciate it.

Sujal Shah -- Chief Executive Officer

Thanks.

Operator

Our next question comes from the line of Jay Olson with Oppenheimer & Company. Please proceed with your question.

Jay Olson -- Oppenheimer and Company -- Analyst

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 more -- have more color on. Is there a projection to complete the enrollment in 3Q based on your currently active 150 size were you need to run or you need to open additional sites as opposed that we see in the past few months? And on the M&A, just wondering what's your view on U.S. and ex U.S.

PBC market for seladelpar. Do you see that as like separate opportunities or it's like one package? And also, if you can comment on whether the cash run rate projections also include the investment in building the commercial infrastructure and also prelaunch preparation? Thank you.

Sujal Shah -- Chief Executive Officer

Yes. Thank you for the question. So 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. 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 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 somewhat independently. The goal within CymaBay is clearly to get seladelpar 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. 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 seladelpar 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. Then finally, you asked a little bit about cash runway.

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 last -- 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 nondilutive sources of capital, as well as a host of other vehicles that we've deployed in the past as well.

So 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 NDA -- post-NDA filing approval and launch. We certainly would look to file the NDA as quickly as possible post top line data. All of that, of course, is already embedded in our projections.

Jay Olson -- Oppenheimer and Company -- Analyst

Great. Thanks for the color.

Operator

Thank you. Our next question comes from the line of Kristen Kluska with Cantor Fitzgerald. Please proceed with your question.

Rick Miller -- Cantor Fitzgerald -- Analyst

Hi, everyone. This is Rick on for Kristen. Thank you for taking our question. We've just got one here.

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 subset of T-cells with high cytokine production and greater proliferation potential, respectively. Given the potential role for seladelpar and 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.

Sujal Shah -- Chief Executive Officer

Thank you for that question. I'll ask Chuck to give some comments here, Chuck?

Chuck McWherter -- Chief Scientific Officer

Yes, I just want to make sure I was off of mute. So thank you for that question. And I think 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 is or is not a role.

We did do a study that we presented an abstract at a recent meeting where we looked at its affecting an immune-mediated fibrosis model, where we saw that seladelpar did decrease both liver and renal fibrosis. So that may be one indication that there may be something there. But 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.

Rick Miller -- Cantor Fitzgerald -- Analyst

OK. Thank you very much.

Operator

Thank you. Our next question comes from the line of Mayank Mamtani with B. Riley Securities. Please proceed with your question.

Yuan Zhi -- B. Riley Securities -- Analyst

Hi. This is Yuan on for Mayank. Since you now close our near enrollment completion, do you have a sense of what portion of the patients have a biopsy taken?

Sujal Shah -- Chief Executive Officer

Yes. 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've 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 fair liver biopsy. We're, of course, encouraging patients to do so, 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 ENHANCE 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.

Yuan Zhi -- B. Riley Securities -- Analyst

Got it. Thank you for the additional color. 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?

Sujal Shah -- Chief Executive Officer

Yes, it's a good question. 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 seladelpar, 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 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 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.

Yuan Zhi -- B. Riley Securities -- Analyst

Thank you for the additional color. That will be all.

Operator

Thank you. Our final question comes from the line of Thomas Smith with SVB Securities. Please proceed with your question.

Mike Kratky -- SVB Leerink Partners -- Analyst

Hi, everyone. This is Mike on for Tom. 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?

Sujal Shah -- Chief Executive Officer

Yeah. It's a great question. And you talked a little bit about sales starting to plateau, and I presume you're referring to obeticholic acid. When we think about seladelpar, we think there are a number of key opportunities.

First of all, in those patients who are clearly in complete responders to first-line treatment with ursodeoxycholic acid, there's a need for greater efficacy, not just in reducing cholestasis and inflammation but really starting to normalize biochemical response in patients. So that's one thing we think seladelpar is quite differentiated from even obeticholic 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 obeticholic acid can potentially cause or worsen pruritus in patients with PBC. And so, when we look at some of the data sets with a obeticholic acid, clearly, that impacts their opportunity in the market, and we think seladelpar 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 pruritus 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 seladelpar profile, along potentially with safety. We've seen a couple of label revisions for obeticholic 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, we think is yet a third potential differentiator that would support a much more growing opportunity, say, for seladelpar in just a 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.

Mike Kratky -- SVB Leerink Partners -- Analyst

Got it. That's very helpful. Thanks.

Sujal Shah -- Chief Executive Officer

Thank you.

Operator

Thank you. Our next question is a follow-up from Mayank Mamtani with B. Riley Securities. Please proceed with your question.

Yuan Zhi -- B. Riley Securities -- Analyst

Thank you. One more question from us. It seems like one of your peers that have phase three data are slightly ahead of you guys. So we are wondering how are you anticipating that to shift the narrative for what the expectation should be for RESPONSE? And do we know if they will have more severe patients included? Thank you.

Sujal Shah -- Chief Executive Officer

Appreciate the question. So I presume you're referring to the ongoing development of elafibranor in patients with PBC, where we did hear the sponsor referred to completing screening last month. Our projection is with the run-in period that usually goes beyond screening that that study could potentially enroll here in the coming weeks, if not toward the end of this month. 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 in addition to just RESPONSE, the ASSURE data set, we think, gives us a tremendous amount of 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 elafibranor 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 in powering RESPONSE not just for the primary and key secondary end point around biochemical response and normalization of biochemical response but also around treating pruritus that's something that we think we're advantaged around given our prior data sets. So 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 seladelpar quite well against other potential treatment alternatives.

Great. Thank you for taking our questions.

Appreciate it. Thank you.

Operator

Thank you. There are no further questions at this time. I'd like to turn the conference back over to Mr. Shah for any closing remarks.

Sujal Shah -- Chief Executive Officer

I appreciate it. So 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 seladelpar in PBC. We believe we are well positioned with a strong balance sheet and a highly derisked 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.

Operator

[Operator signoff]

Duration: 62 minutes

Call participants:

Paul Quinlan -- General Counsel

Sujal Shah -- Chief Executive Officer

Dan Menold -- Vice President, Finance

Emma Nesson -- Piper Sandler -- Analyst

Chuck McWherter -- Chief Scientific Officer

Steven Seedhouse -- Raymond James -- Analyst

Patrick Dolezal -- LifeSci Capital -- Analyst

Ed Arce -- H.C. Wainwright -- Analyst

Jay Olson -- Oppenheimer and Company -- Analyst

Rick Miller -- Cantor Fitzgerald -- Analyst

Yuan Zhi -- B. Riley Securities -- Analyst

Mike Kratky -- SVB Leerink Partners -- Analyst

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