CymaBay Therapeutics, Inc.
Q2 2020 Earnings Call Transcript

Published: 11 Aug 2020

[Operator:]

Greetings. And welcome to CymaBay Therapeutics’ Second Quarter 2020 Earnings Conference Call. At this time, all participants are in a listen-only mode. A question-and-answer session will follow the formal presentation. [Operator Instructions] As a reminder, this conference maybe recorded. I would now like to turn the conference over to your host, Dan Menold, Vice President, Finance. Please proceed, sir.

[Dan Menold:]

Thank you, Operator, and good afternoon, everyone. I hope that you’ve had a chance to review the press release we issued announcing our second quarter 2020 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 Dr. Chuck McWherter, Chief Scientific Officer; and Klara Dickinson, Chief Regulatory and Compliance Officer. Sujal will provide an update on recent progress and plans on the development program for seladelpar, as well as brief summary of our financials before we open the call up 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 and anticipated timelines and data release dates, and cash runway 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:]

Good afternoon and thank you for joining us. Given our discussion of ENHANCE data and plans for continued development of seladelpar in PBC just last week. Our prepared remarks today will be brief and will focus on four specific topics, key achievements in the first half of the year, planned development activities, upcoming milestones and summary financials. Over the past two months, we have experienced quite a reversal of fortunes triggered by the conclusion of an in depth, rigorous and independent analysis and review of safety data in the second quarter from a Phase 2 study of seladelpar in patients with nonalcoholic steatohepatitis or NASH. First, the FDA lifted all clinical holds across all three liver diseases, in which seladelpar had ongoing clinical studies that were halted late last year, namely NASH, primary biliary cholangitis or PBC and primary sclerosing cholangitis or PSC. FDA took this action in short order, following receipt of CymaBay’s admission of complete responses for each indication that included an independent report from a panel of some of the world’s most renowned hepatal pathologist [ph] and hepatologist expert in NASH and drug-induced liver injury and the supporting data package that led to their unanimous conclusion that there was no clinical, biochemical or histological evidence of seladelpar related liver injury in the NASH Phase 2 study and that pending FDA review, clinical development of seladelpar should resume. Then barely over a week after the FDA lifted all clinical holds of seladelpar, we unblinded and reported positive topline results from ENHANCE, a global Phase 3 study of seladelpar in patients with PBC that was terminated early, in which the amended primary and two key secondary endpoints were met with statistical significance. For patients on seladelpar 10 milligram, the results included a nearly 80% response on our primary composite endpoint and accepted regulatory approval endpoint versus 12.5% on placebo, almost 30% response on ALP normalization versus zero on placebo and a meaningful and significant placebo-controlled effect on reducing pruritus, a key clinical symptom of PBC all in just three months. In addition, seladelpar appeared to be safe and well-tolerated in this study. We believe these data continue to support the potential for seladelpar to be a breakthrough therapy for patients with PBC. And I’ll remind you that in the U.S. seladelpar has breakthrough therapy designation from the FDA and in Europe, prime access designation from EMEA for PBC. The full details of this data were discussed last week and a recording of the call is available on our website. The full set of data from this study are being reviewed in detail and will serve to inform design considerations of a new Phase 3 study. We believe the results from ENHANCE, results from previous Phase 2 studies and our growing safety experience with seladelpar in patients with PBC have the potential to support a smaller overall study focused on comparing seladelpar 10-milligram with placebo. We are confident that once finalized and approved by regulatory authorities both in and outside of the United States, the global Phase 3 study will be one that we can utilize our experience to enroll and execute expeditiously. We are moving quickly to finalize the design of this study, submitted to regulatory agencies and begin study startup activities that will continue through the remainder of this year, with the expectations that enrollment in a new Phase 3 study is likely to begin in the first quarter of 2021. We also hope to have the opportunity to present data from ENHANCE at an upcoming medical meeting, potentially at AASLD in November. In addition to the Phase 3 study, we plan as quickly as feasible to reinitiate the long-term study also terminated last year. This will provide the more than 100 patients previously treated with seladelpar in the study to once again receive treatment with seladelpar while allowing us to continue building the safety database in support of an NDA. We intend to allow all PBC patients previously enrolled in a seladelpar study the opportunity should they qualify and have support of their treating physician to participate in our long-term study, in a new Phase 3 study or in any of the other NDA enabling or supported studies we initiate to support registration. For each of these studies, we also plan to incorporate necessary procedures to ensure patient safety in consideration of the current global pandemic involving COVID-19. Turning briefly to seladelpar programs beyond PBC, let me say a few words about PSC and NASH. When we halted development of seladelpar late last year, we had just begun a dose ranging Phase 2 study of seladelpar in patients with PSC, a orphan cholestatic disease that shares some attributes with PBC, but for which key differences can make it a more heterogeneous and complex disease to treat. Many patients with PSC also suffer from inflammatory bowel disease, have significant liver inflammation and fibrosis, and have a significant risk for developing cholangiocarcinoma. We continue to believe the anti-cholestatic, anti-inflammatory and anti-pruritic effects observed with seladelpar in PBC and the potential anti-fibrotic effects of seladelpar warrant exploring its safety and efficacy in patients with PSC. While we will remain highly focused this year on reinitiating the development program for seladelpar in PBC, we will continue to consider how and when we may look to reinitiate our development efforts in PSC and provide updates appropriately. There are currently no approved treatments for PSC and we continue to believe there may be a significant opportunity for us to explore seladelpar in this indication. With respect to our development of seladelpar in NASH, earlier this year we shared topline results for seladelpar on endpoints of NASH resolution and fibrosis in our Phase 2 study. The effects on the two key endpoints accepted by regulatory authorities for registration in NASH was particularly encouraging for the seladelpar 50-milligram dose group versus placebo. For patients in the seladelpar 50-milligram dose group, 26.1% experienced NASH resolution with no worsening of fibrosis and 37% experienced at least 1 point improvement in fibrosis with no worsening of NASH versus 8% and 20% for these two endpoints, respectively, for patients in the placebo group. We believe these data, along with the improvements in lipids, and overall safety and tolerability profile observed for seladelpar in the study and the ease of its administration as an oral agent, position seladelpar well to be combined with other complimentary mechanisms being evaluated in NASH today, particularly those that have demonstrated effects on weight loss and reductions in total liver fat. Given the multifactorial nature of NASH and the significant resources required to establish safety and efficacy in clinical studies, we believe a thoughtful combination strategy and the potential opportunity to advance development through partnerships or collaborations is not only warranted, but would be the most optimal development path forward. We will look to upcoming medical meetings once again, potentially AASLD in November as an opportunity to share the full data from this study, and in parallel, we’ll evaluate the best strategic path forward, while our focus and capital resources remain on re-initiation and completion of the development program for seladelpar in PBC. Finally, I’d like to highlight a brief summary of our key financial highlights from the second quarter. We have concentrated intently on reducing expenses since the end of 2019 and the impact of this effort was particularly evident in the second quarter by the magnitude of our overall cost containment. While still in the midst of our investigation of NASH findings and expert panel review, we had guided to a June 30, 2020, expected cash balance of between approximately $156 million to $161 million. This forecast was based on a six-month expected cash burn of between $30 million and $35 million, incorporating costs associated with termination and close out of contracts and clinical studies, severance benefit payments associated with previously announced headcount reductions and expenses for ongoing operations that were largely focused on the investigation and regulatory efforts that ultimately led to a lifting of the clinical hold for seladelpar, as well as advisory and consulting expenses associated with our ongoing evaluation of strategic options. The financials that we report today reflect the focus and discipline of how we operate our business. We successfully dealt with the unexpected and rapid challenges of the Coronavirus pandemic, delivered on resurrecting the promise of seladelpar for patients and our shareholders, while sharply decreasing the second quarter cash expenditures to $7.3 million. This translates to a total cash burn during the first six months of the year of approximately $22 million greater than 25% lower than the low-end of our prior guidance. While some of this cash savings is due to a temporary delay and the timing of certain clinical trial shutdown costs, a portion also reflects certain cost savings due to the company’s rapid resolution of the clinical hold on the seladelpar program and the completion of our review of strategic options, much sooner than initially planned in our cash forecast. Cash, cash equivalents and short-term investment totaled $168.9 million at June 30, 2020. We have not raised capital since the first quarter of 2019 and we believe our current cash is sufficient to fund our current operating plan, including the re-initiation of the full development program for seladelpar in PBC into 2022. Due to the ongoing impact of the global Coronavirus pandemic, we continue to conduct operations remotely for all employees, which has allowed business activities to continue as seamlessly as possible. To-date, these developments have not had a significant impact on our financial condition or our ability to execute our business plan. We will continue to closely monitor pandemic development and their associated risks to the business, including plans to restart clinical development of seladelpar and will continue to take actions available to mitigate them where possible. Further, all of our actions will be guided by a commitment to taking all steps possible to ensure the health and safety of our employees, as well as patients enrolled in our clinical studies. We’re now happy to take questions. Operator?

[Operator:]

Thank you. [Operator Instructions] Our first call comes from Yasmeen Rahimi with Piper Jaffray. Please proceed with the question.

[Unidentified Analyst:]

Hi, team. Paul [ph] on for Yasmeen. Congrats on all the progress this quarter. Two questions today. First, what do we know about the market size for UDCA treated patients, who are biochemically controlled, but still experienced significant levels of pruritis? And second connected to that question, how could an additional cohort be incorporated into the upcoming Phase 3 PBC trial to support an additional label indication of pruritis reduction in UDCA treated biochemically controlled patients. Thanks for taking our questions.

[Sujal Shah:]

Thank you for the question. So let me maybe start off and perhaps invite other team members to add any additional color. We’ve not really done an in depth analysis fundamentally around what we would consider a commercial opportunity for pruritus, particularly patients that maybe adequately treated as the -- as you’re asking on UDCA itself. I think what I can point to, however, is the fact that, despite a good portion of patients having some benefit and even those having benefit that’s deemed adequate to UDCA. UDCA is not in fact, as you know, been associated with necessarily improving the symptom of pruritus in patients with PBC. So we do believe that overall, with the opportunity to potentially have an indication or label claim, or even data in a final Phase 3 study for registration that supports what we’ve seen thus far in ENHANCE where seladelpar shows a significant benefit on reducing pruritus relative to placebo at the 10-milligram dose group. There may in fact be opportunities for us to continue to expand use in the overall PBC population. Now, I think part of your second question is, whether or not there may be ways for us, of course, to incorporate this endpoint, if you will or potentially another arm in the next Phase 3 clinical study. And so here, perhaps, what I’d like to be able to highlight is, the most significant need today remains for these patients that remain at risk of disease progression. So those patients that are either inadequate responders to UDCA or are intolerant, continue to have a significant need for a safe, efficacious, well-tolerated second-line treatment alternative. Fundamentally, we want to do everything we can to accelerate the execution of a new Phase 3 clinical study to get seladelpar registered for this patient population. Now, we will certainly be exploring the measure of pruritus in the next Phase 3 study as we have an ENHANCE and that along with other potential strategies, could in fact allow us to have multiple avenues to explore the effects of pruritus, not just in the second-line treatment alternative setting, but also for patients at large. These will all be considerations that I think our team focuses in on with experts, with patient advocacy groups, as we think about the overall development program for seladelpar moving forward.

[Unidentified Analyst:]

Okay. Thanks so much for your answers.

[Sujal Shah:]

Thank you.

[Operator:]

Our next question comes from Steve Seedhouse with Raymond James. Please proceed with your question.

[Steve Seedhouse:]

Yeah. Thanks so much. Two questions. First one is just on the PBC Phase 3 study with respect to running a study of 10 milligram versus placebo that enables a smaller Phase 3 could enroll quicker. Just curious if you can talk about whether or not the data you already have from titration or lower doses would still support those options in an eventual label even if you don’t have those arms in Phase 3?

[Dr. Chuck McWherter:]

Yeah. Hi, Steve. Chuck McWherter here Yeah. We do think we have a considerable dataset with both safety and anti-cholestatic effects in our open-label study. So the 50 milligram group really carried, sorry, the 5 milligram group carried over more than 50 patients through a year with good durability and response. And so I think that that really would if we needed a lower dose, we would be able to have that available. Our view though is the 10 milligram dose really shine, I mean, shows really as you’ve seen in the dataset that we released really great effects on alkaline phosphatase, some decreases in bilirubin and a host of other liver chemistries were improved and the safety aspects of the drug really support it going forward as the preferred dose for patients.

[Steve Seedhouse:]

Makes sense. There is no reason to go lower, I guess, if the safety profile is just fine at 10 milligram. And the second question is, you spoke Sujal confidently about PSC on this call, whereas some of your recent updates focused on more on PBC, and obviously, that being the priority. But now that PSC is looks like a second priority for you. Can you just talk about if you have any data from patients treated in the terminated Phase 2 study, if that’s informing your competence here or -- and/or if you’ve seen an evolution in really an understanding of what endpoints matter most and the type of trial design that the FDA would prefer, or does that last part remain a bit unclear still? Thank you.

[Sujal Shah:]

Yeah. Thank you for the question. It’s a good question. I think, first, I’d start off with the fact that I don’t think our perspective fundamentally despite the challenging situation we’ve been through over the last nine months really changes our outlook on PSC relative to where it was last year when we had embarked on the Phase 2 dose ranging study in that setting. I think we’re largely encouraged by the fact that as a cholestatic liver disease, we are likely to see some benefit for patients certainly on improving cholestasis, given the mechanism of seladelpar and what we see in terms of reductions in transaminases in the PBC population. We’re encouraged by the potential that seladelpar may in fact be also highly anti-inflammatory in what is cholestatic disease with a greater degree of inflammation and even fibrosis. I think, one nuance point is the initiation and progression of fibrosis in NASH is quite unique to NASH and not necessarily the same as what occurs in PSC. Nevertheless, the mechanism and even what we’ve seen in NASH, I would say, gives us some encouragement about the potential to see some anti-fibrotic benefit even in a PSB population. Again, I caution that the etiology of fibrosis is unique in these two diseases. But I do -- I would say, that we are in fact currently encouraged by what we’ve seen now across both now the PBC and NASH populations. So really as we think about our focus in rare orphan cholestatic diseases where there remains significant unmet needs for patients. That’s really the key driver in our thoughts around continuing to expand seladelpar in -- from PBC into PSC. I think as I mentioned in the prepared remarks, the key thoughts on our end are just about timing and how we would actually progress, and I think, it’s a bit premature for us to be able to provide specific guidance there. But this is a patient population that again we do believe there is a potential for us to explore development.

[Steve Seedhouse:]

Okay. Thanks. And just to follow up, did you have any data from the terminator study or is there just not enough there?

[Sujal Shah:]

No. We had actually only randomized the single subject in that Phase 2 study when we halted development at the end of last year and it was the subject actually on placebo. So no data in that population as of yet.

[Steve Seedhouse:]

Got it. Thanks so much. Appreciate it.

[Sujal Shah:]

Thank you, Steve.

[Operator:]

Our next question comes from Eliana Merle with Cantor Fitzgerald. Please proceed with your question.

[Eliana Merle:]

Hi, guys. Thanks so much for taking my question and congrats on all the progress. Just in terms of development plans in NASH, it seems like a collaboration approach is something that you’re exploring. What could make that change where you would consider developing seladelpar NASH by yourself, I mean, I know that it’s a complex space with large studies, but you did see some encouraging histology data on fibrosis and NASH resolution. I am so curious sort of what could change your outlook in terms of developing it yourself first then collaboration? And then also just in terms of the learning of PPARd delta biology and so what we learned from your NASH pathology data versus what we’ve seen in NASH from other PPARd such as alpha or gamma. What do you think this means for PBC long-term, I know that there is other PPARd in development for PBC as well? So in terms of what we learned about PPARd biology from the NASH data. What do you think this means long-term for the competitiveness of your data in PBC long-term? Thanks.

[Sujal Shah:]

Yeah. Thank you for the question, Eli. Let me answer the first one and then I will ask Chuck to provide some color around seladelpar and PPARd delta specifically. Yeah, I think when we look at the dataset in NASH, as I mentioned, we are in fact highly encouraged by what was observed particularly at the 50 milligram dose group on both NASH resolution and fibrosis. And this was a relatively small study however. And as we think about what this data informs us, I think, it tells us quite a bit around the ability for seladelpar to provide some of the key benefits that NASH patient would require to treat the overall disease. At the same time, the totality of the data also gives us a pretty clear understanding, and I think, this is the case frankly I’d have to say for other agents in development as well around thoughts on what would be the best combinations in order to truly have substantial benefit in a population of NASH patients. And I talked about this specifically as showing some significant and meaning benefit relative to placebo alone, which I’d argue many agents have either shown no benefit or marginal one. So much of our thought actually comes from the fact that if we were to design the most optimal development strategy, it would in fact be one in which we have some better understanding around complimentary mechanisms to seladelpar to drive the kind of response that we believe you really want to be able to see to open up on this large patient population. Now, of course, there is no question that this also requires significant resources. So, but it’s a combination of both the optimal resource, as well as the most optimal development plan that really informs us of wanting to make sure that we have this opportunity to explore some of these potential combinations.

[Dr. Chuck McWherter:]

Hi, Ellie. This is Chuck. Maybe I’ll just kind of add in some additional information around different profiles for PPARd. The first thing I would want to caution everybody is about some of the challenges of making comparisons across studies where they’re not head-to-head, sometimes there can be even minor differences in the population. So it always comes with some big qualifiers. I would say that if you looked at Resolve versus our Phase 2b, as you know, in Resolve that there was no effect on fibrosis where we’re although we didn’t hit statistical significance either, I think due to the small size of the study only 46 milligram and the 50 milligram group. So it’s very heartening to see 37% of patients with an improvement in one stage in fibrosis versus 20% in placebo. And then if you focus on some of the differences between an alpha delta and a strong delta, I point out the effects that we see on, for example, markers of liver injury. So ALP reductions at a year were about 38 units per liter with seladelpar and 50 milligram placebo was very minor and that is very different than what was seen in either GOLDEN-505 or in Genfit’s Phase 2 study that they presented last year in Indiana. And of course, we haven’t seen all the data on Resolve they had, so that’s to be determined. And then if you turn to PBC, I think this is where the story really strengthens for seladelpar and the effect of delta. It’s not only on bile acid reduction and improving a cholesterol disposition, which helps to reduce the hepatocellular stress, but the reductions that we’ve seen in markers of inflammation and stress like ALT both an ENHANCE and in our open-label Phase 2 study really I think encourage us to think that delta really provide everything that the patient will need. If you then think about the pankipar [ph] elafibranor in the native results that were provided just a month or so ago, you see that, once again, I think, if you look at the fibrosis affects 37% versus roughly 40% and then the placebo rates were very similar again. Again, they had a much larger study and it was a long -- it was a shorter study, it is only a 24-week study. So there, again, I think that, what elafibranor and seladelpar having common may be the delta component. In fact, I know that there is a publication that just appeared it’s in had a print in journal hepatology, where the authors basically come to the same conclusion that the anti-inflammatory effects of elafibranor are driven by delta.

[Eliana Merle:]

Got it. Very helpful. Thank you.

[Sujal Shah:]

Thanks, Eli.

[Operator:]

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

[Ed Arce:]

Hi, everyone. Thanks for taking my questions and congrats on remarkable turnaround in the last few months. I just wanted to perhaps drill a bit further in some of your remarks Sujal just now with regards to NASH and your decision strategically to focus on looking to partner that program going forward? And I wanted to see if you could just give us a bit more detail around your thinking in that strategic decision with regard to your overall focus as a company in rare cholestatic liver diseases and how that played a part of your overall decision and along with that, if you’ve had any sort of preliminary discussions with any potential partners? Thanks.

[Sujal Shah:]

Yeah. Thank you, Ed. Yeah. Let me maybe start off by just saying that, we’re passionate and compelled by the dataset we already have in hand for the benefits that we’re seeing to-date with seladelpar and PBC. We fundamentally believe there is a significant opportunity to advance care for these patients. That’s not fully reflected for example and where even the company is valued today. We think about those patients and the significant needs for those patients, we frankly believe that there is an opportunity to even expand the overall patient population based on the latest profile of seladelpar are coming out of ENHANCE and so that keeps us incredibly laser focused on getting seladelpar in the hands of these patients. So when we think about NASH then, obviously an area of significant high unmet need as well. There still remain a significant number of open questions, whether they’re clinical, regulatory or even commercial. I think it’s fair to say that a lot of questions we all felt might be answered by now in the setting of NASH remain unanswered. And so we have an opportunity with a very clear dataset we have in hand with seladelpar and PBC to drive forward and to do the things that we fundamentally need to do to create value and to do so in a very capital efficient manner. As I mentioned, we’re incredibly confident in the overall cash balance we enter the second half of the year with and our ability to really execute our operating plan into 2022. And so will remain very focused on this key opportunity, while some of these questions in NASH are ultimately answered, particularly again as it pertains to regulatory, as well as eventually commercial opportunity. I think as we look at the data, we like to always say that the data really needs to drive our decision making. And I would tell you that I think it’s the data for seladelpar that keeps us encouraged, but also has us focused on thinking of complimentary mechanisms to which seladelpar can be combined. So when we talk about partnerships, these can be even a collaboration that are non-exclusive. They don’t necessarily have to be arrangement with an exchange of economics. They’re really driven towards thinking about again a thoughtful development approach to getting meaningful benefit in the population. So we’ll continue to spend some time thinking about these opportunities. But again, won’t take away our operating focus on the opportunity that’s most near-term to bring seladelpar to patients with PBC.

[Ed Arce:]

That’s very helpful, Sujal. Thanks for that. And then just perhaps one other question on your planned pivotal study for PBC, realize enrollment is targeted to begin first quarter of next year. When do you think you might be in a position to discuss the full protocol for the study and trial design?

[Sujal Shah:]

Yeah. That’s a good question. Thank you, Ed. I think, as I mentioned currently, what we’re making sure that we do is to delve into the dataset in front of us now to inform the final study design that will put in front of regulatory agencies. So we plan to continue to move that forward as expeditiously as possible with the idea that we do want to be thoughtful with the dataset we have in hand, particularly the full data set from ENHANCE. I think when we think about timelines through the rest of this year, as I mentioned, the key will be for us in the relatively short-term to put a protocol in front of regulators. As soon as we have any of their input or require a need for any kinds of changes to that protocol or the green light to advance, we’ll put it in front of IRBs and ethics committees very quickly. Our, again, as I’ll remind folks ENHANCE was a study that was conducted in over 100 centers across more than 20 countries globally. And so our experience here I’m confident will give us the opportunity to get back up and running as quickly as possible. But we do have to go through those necessary steps, of course, with regulators, ethics committees and investigational review Boards. And so that will be -- those will be activities that remained through the rest of this quarter and early into the fourth quarter as well. I think in the end, it’s hard for us to say what the timing would be for those groups to get back to us. But we’ll start the study as quickly as possible, if we get through a process where those approvals come even before the end of this year, there won’t be anything that holds us back from beginning enrollment even sooner. I just wanted to make sure that we set the proper expectations around overall timeline.

[Ed Arce:]

Fair enough. Thanks Sujal.

[Sujal Shah:]

Thank you.

[Operator:]

Our next question comes from Jay Olson with Oppenheimer. Please proceed with your question.

[Jay Olson:]

Oh! Hey. Thanks for taking the question. I was wondering if you could maybe look into the future at the PBC market dynamic with potentially other new entrants in addition to seladelpar including intercepts own combination of OCA with bezafibrate and just speculate as to how you think those market dynamics may shake out?

[Sujal Shah:]

Yeah. Thank you for the question, Jay. I think when we think about the unmet needs for patients today, we know that there are patients that remain inadequate responders even to second-line treatment. We also know that patients continue to suffer from symptom burden. So, overall, those are two of the key things that we know from a rich set of data with seladelpar, particularly relative to some of these other agents, as you mentioned, that are looking to be explored in the population. This is a rich set of data that continues to provide us content. In fact, I believe that the data that we have in hand relatives for example to things like bezafibrate or elafibranor where sponsors have discussed advancing these treatments into development. I would argue that our dataset in terms of overall patients studied in Phase 2 and even in our ENHANCE Phase 3 study is a more rich dataset overall in a very well-controlled global study. So I can’t speak necessarily to what those agents may show. I don’t have that forward crystal ball. But I can tell you that the experience with seladelpar for patients is one that’s been very positive. There is a tremendous amount of experience with physicians, as well as patients globally with seladelpar. And I think that gives us a tremendous advantage as we look to reinitiate development, maybe I’ll ask Chuck to provide some of his thoughts on top of that as well.

[Dr. Chuck McWherter:]

Yeah. Thank you, Jay. So just to add a little bit to what Sujal was describing, I think, one common to think about is, you know, some of the combination strategies for example bezafibrate and OCA are really trying to go after subjects who are not receiving, a complete response on the single agent. So it’s designed to address maybe a shortfall or a perceived shortfall in terms of benefit to the patient. And I think seladelpar profile as exhibited in ENHANCE really speaks to its ability to help address that at least in some aspects. Another thing to consider and we alluded to this earlier, with the trend among medical experts to think about lower alkaline phosphatase is always a good goal. If you can normalize it, that’s an advantage. So there currently, patients who have alkaline phosphatase that are below let’s say 1.67, upper limit and normal for our candidates for entering clinical studies. They still carry risk. They still etch and so I think seladelpar’s profile as we think about potential strategies with clinical data to expand the addressable population, I think really both bodes well if we could, for example, in a lifecycle management approach, think about exploring its activity and patients who still have elevated outfox with a drug that’s well-tolerated. That would be an advantage over some of the other agents that you alluded to that carry some tolerability issues. It’s more challenging for them to go into lower risk populations where maybe the tolerability does not set the benefit as much.

[Jay Olson:]

Thank you. That super helpful maybe as a follow on. I was wondering if assuming that seladelpar’s efficacy, safety and tolerability profile continues to look as favorable as they do in your registrational study. Would you consider studying seladelpar in a first-line setting potentially impatient to can be identified in advance as potentially unresponsive or intolerant of UDCA?

[Sujal Shah:]

Yeah. I absolutely think that our intention is really to understand the benefit and the safety of seladelpar in PSC patients. First the intended population for the program that we’re pursuing right now, but ultimately, in the broadest population for which there might be benefit. And so, I’m not here to say that we’re going to try to establish that it’s front-line therapy at the moment. But I wouldn’t rule it out. I think it would be quite interesting to take patients who are naive to UDCA and conduct a study to see what the benefit might be. And I think that physicians and patients alike would be interested in the outcome of a study like that.

[Jay Olson:]

Great. It’s super helpful. Thanks for taking the question.

[Operator:]

Our next question comes from Thomas Smith with SVB Leerink. Please proceed with your question.

[Thomas Smith:]

Hi, guys. Thanks for taking the questions. Just a couple questions on PBC, I guess as we look forward to a potential data presentation at AASLD. Could you give us a sense of what additional data sets we should been looking for from the ENHANCE studying, can we see additional data looking at symptom burden or the ability to improve pruritus beyond just the NRS data that he presented in the topline release? And then could you also just remind us besides the new Phase 3 study, which trials are clinical activities with remain as kind of the gating factors that you would need to complete prior to submitting an NDA for PBC? Thanks.

[Sujal Shah:]

Yeah. Thanks for that question. Yeah. I think we’re going to be receiving additional datasets now. So the dataset that we received a little more than a week ago were the topline data. So we would have an expectation to be able to review a variety of information including exploratory biomarkers, patient symptom responses things like that that I think that we’ll try to understand first. So we’ll let the data drive us what’s the most interesting that we would like to combine with what we’ve already released. But I think you can look forward with anticipation to really I think a very nice dataset, and remains to be seen whether we’ll be accepted AASLD, but that’s really our hope and our intention.

[Dr. Chuck McWherter:]

Maybe I’ll ask Klara, our Chief Regulatory Officer and Compliance Officer to talk a bit about the overall development program in some of these other studies.

[Klara Dickinson:]

Thank you. Thank you for that question. Some of the additional studies are just the ancillary studies that most companies have to conduct. One is renal impairment studies, drug interaction studies, looking at your product to be marketed formulations, full effect studies. And then we do have also a specific study that’s looking at hepatic impairment in our patient population of patients with PBC and there is a classification based on Chelsea’s data.

[Thomas Smith:]

Okay. Got it. That’s helpful. Thanks very much.

[Sujal Shah:]

Thanks Tom.

[Operator:]

Thank you. At this time, I would like to turn the floor back to management for closing comments.

[Sujal Shah:]

Thank you. I’d like to make just a few comments as we close today. It’s been a remarkable year to say the least for CymaBay, for our patients and for all of our stakeholders. In our most difficult days at the company, we found the will to investigate to analyze, to learn, to forge a path forward and simply just keep fighting to make progress from the patient so we left behind late last year. Today I spent several hours with members of our team speaking to leaders of several PBC and liver disease patient advocacy groups around the world. We have been giving these groups, as well as investigators and update on what we learned and what we plan to do next. I can’t even begin to describe how important the human element is in everything we all do every day. Whether our motivation comes from a desire to support our colleagues, patients and their families, the medical communities are those groups who have invested in us at CymaBay to create value. We are grounded by the human element and everything we do. I can assure you that we will continue to be focused on playing our part, focusing on improving the lives of patients with liver diseases. We’ll continue to do so thoughtfully, with patients at the forefront of our mind and efficiently to ensure we are meeting our obligations to all of our stakeholders. As I mentioned, we are confident we have the capital needed to reinitiate development of seladelpar and I expect them to continue achieving key milestones and providing updates in the months ahead and look forward to our next call. Thank you all again for joining us today.

[Operator:]

Thank you. This does conclude today’s teleconference. You may disconnect your lines at this time and thank you for your participation.