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CymaBay Therapeutics Inc (CBAY) Q4 2018 Earnings Conference Call Transcript

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CymaBay Therapeutics Inc  (NASDAQ: CBAY)
Q4 2018 Earnings Conference Call
Feb. 28, 2019, 4:30 p.m. ET

Contents:

  • Prepared Remarks
  • Questions and Answers
  • Call Participants

Prepared Remarks:

Operator

Good day, ladies and gentlemen, and welcome to CymaBay's Fourth Quarter and Year End 2018 Financial Results Conference Call. At this time, all participants are in a listen-only mode. Following the formal remarks, we will open the call for your questions. Please be advised that the call will be recorded at the Company's request. It is also being webcast live on the Investors section at the CymaBay website at www.cymabay.com.

Now I would like to turn the call over to Mr. Dan Menold, Vice President of Finance at CymaBay. Mr. Menold, you may proceed.

Daniel Menold -- Vice President of Finance

Thank you, Operator, and good afternoon, everyone. Hopefully by now you all have had a chance to review the press release we issued announcing our year-end 2018 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; Dr. Pol Boudes, Chief Medical Officer; and Dr. Chuck McWherter, Chief Scientific Officer. They will provide an update on our financial position and clinical program and review upcoming milestones before we open up 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, 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 forecasted due to impact of many factors. The Company assumes no obligation to update or supplement any forward-looking statement, 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 A. Shah -- President and Chief Executive Officer

Good afternoon, everyone. And thank you for joining us. It's already been a busy start to the year for us at CymaBay. During the call today, we will focus on our most significant accomplishments and importantly on key upcoming milestones that have the potential to meaningfully increase future value and to establish CymaBay as a leader in addressing the unmet needs for patients with liver disease. As I spend time speaking with investors, I sometimes hear that CymaBay is under the radar or under appreciated, given the de-risk profile of seladelpar and its potential to provide an improved treatment alternatives for patients with inflammatory liver disease. The advances we made in 2018 and thus far in the first few months of 2019, have positioned us to transform that sentiment into one were the promise and opportunity of CymaBay will be more widely appreciated.

We ended 2018 with two major achievements in the development of seladelpar for patients with primary biliary cholangitis or PBC. We initiated our first ever Phase III registration study and for the third consecutive year, we made a late breaking presentation of Phase II data at the AASLD's Liver Meeting. Earlier this month, we announced two additional significant accomplishments. First, we announced the FDA granted seladelpar breakthrough therapy designation for treating patients with PBC.

And second, we completed enrollment of a Phase IIb proof of concept study of seladelpar in patients with nonalcoholic steatohepatitis or NASH, one quarter ahead of schedule. As we look to the year ahead, we expect to increase the pace of major milestone events and catalysts. By the end of 2019, we anticipate completing enrollment in ENHANCE our global Phase III registration study for seladelpar in PBC and also completing our ongoing Phase II study in PBC for which we have already shared interim data at recent key medical meetings.

In addition, we expect to announce top line data from our Phase IIb study of seladelpar in NASH in the second quarter. And finally, we intend to complete ongoing evaluation and reach decisions regarding other opportunities to expand the development of seladelpar. Let us start with our development program in PBC. As I mentioned, ENHANCE is our global Phase III registration study of seladelpar in PBC that we initiated in the fourth quarter of 2018. This study is designed to establish the efficacy and safety of seladelpar in PBC patients, who have an inadequate response to who are intolerant to UDCA, the current first-line treatment for PBC. Our goal with the study is to support the submission of a global registration dossier with health authorities to obtain approval of seladelpar.

I'll ask Pol to review some of the key elements of ENHANCE. Pol?

Pol F. Boudes -- Chief Medical Officer

Thank you, Sujal. ENHANCE is a 52-week placebo-controlled randomized study with a target enrollment of approximately 240 PBC patients at more than 150 clinical sites in over 20 countries. Patients are being randomized to receive daily doses of placebo or seladelpar at either 10 milligram or 5 milligram with the possibility to increase the dose to 10 milligram after six months. The primary endpoint is the composite responder rate, in which a responder is defined as the patient who achieved an alkaline phosphatase level of less than 1.67 times the upper limit of normal, with at least 15% decrease from baseline and also has a normal level of total bilirubin at 52 weeks.

We are making good progress in this large global study which includes enrolling patients across four regions, North America, Europe, Latin America and Asia-Pacific and are working to complete enrollment in ENHANCE by the end of this year. ENHANCE was initiated on the strength of what we believe to be a very compelling and different safety profile in Phase II, using the same dose regimen, the same duration of treatment and the same key outcome measures that we are using in ENHANCE. We believe that the results in Phase II have helped to derisk the Phase III program by establishing a differentiated profile for seladelpar in efficacy and tolerability as a potential treatment for PBC.

Results from the 52 weeks of treatments in the ongoing Phase II were presented for the first time at the Liver Meeting this past November. We also described positive results at 26 weeks on pruritus or itching, as well as in the subset of patients with cirrhosis at baseline. Each of these presentations from last November and the accompanying press release with additional details can be found on our website. All in all, this Liver Meeting was our busiest medical meeting to date and it provided a forum for critical external evaluation of the sustained anti-cholestatic and anti-inflammatory effect in PBC patients, treated with seladelpar up to 52 weeks.

Very importantly, and in contrast to the only approved second-line treatment today, the potential benefit of seladelpar on cholestasis and inflammation were seen without worsening of in pruritus. The most common clinical symptom of PBC and one that adversely affect patient's quality of life. The data from our ongoing Phase II study suggest the potential that seladelpar may in fact improve pruritus in patients with PBC. On a fact, we will look to confirm in ENHANCE.

To recap, we believe that seladelpar has the potential to serve the two key unmet needs in patients with PBC, namely improve efficacy and better to our ability. Improved efficacy is believed to be linked to reduce risk of disease progression based on AP reduction as a surrogate in a greater number of patients, and better tolerability has the potential to foster better compliance, while potentially improving overall quality of life of patients.

Sujal?

Sujal A. Shah -- President and Chief Executive Officer

Thank you, Pol. I want to turn to a major accomplishment in the PBC program that we announced earlier this month. The FDA has granted breakthrough therapy designation for seladelpar for the treatment of early stage PBC. In determining to grant this designation, the FDA examines the clinical evidence for substantial improvement over existing therapy. We believe that this decision by the agency reflects the importance of the existing Phase II seladelpar clinical data and the potential for seladelpar to be a substantially improved alternatives over existing treatment for patients with PBC.

The benefit of the breakthrough therapy designation include those of fast-track designation with greater FDA guidance on development efficiency, organizational commitment involving senior managers, as well as eligibility for rolling review and priority review. Seladelpar has also been awarded the corresponding PRIority MEdicine or PRIME designation by the European Medicines Agency. Together, these programs provide an opportunity for enhanced dialog with regulatory authorities and are expected to facilitate the path for potential approval of seladelpar in PBC.

Moving to our NASH development program. We were very pleased to announce completion of enrollment in our Phase IIb study of seladelpar approximately one quarter ahead of schedule.

I'll turn the call over to Chuck to provide an update on this study.

Charles A. McWherter -- Senior Vice President and Chief Scientific Officer

Thanks, Sujal. A total of 181 patients with a baseline biopsy confirm diagnosis of NASH with fibrosis have been randomized into this comprehensive dose ranging double-blind placebo-controlled study. Prior to a baseline biopsy, subjects were required to have a liver fat content, greater than 10% using the magnetic resonance imaging proton density fat fraction or MRI PDFF method. Subjects were randomized in a 2:2:2:1 ratio to receive once daily either seladelpar,10, 20 or 50 milligrams or placebo. In addition, subjects were stratified at randomization by the stage of liver fibrosis and the presence or absence of Type 2 diabetes. Evaluation of baseline liver histology confirmed that subject had well established NASH with a mean NAFLD Activity Score of 5.2.

Additionally, 150 subjects or approximately 83% of patients enrolled had Stage 2 or 3 fibrosis at baseline. The primary efficacy outcome is the relative reduction in liver fat by MRI-PDFF at 12 weeks. Important secondary measures are the evaluation of the histological improvement at 52 weeks in NASH pathology and fibrosis using paired liver biopsy samples. Additional planned assessments include MRI-PDFF evaluations at 26 and 52 weeks. Magnetic resonance elastography and other non-invasive imaging technologies, multiple biochemical markers and an innovative digital liver pathology evaluation using machine learning algorithms.

We believe the screening approach in the study led to a higher proportion of subjects with F2 and F3 fibrosis than has been seen in similar recent Phase II studies. The patients enrolled are reflective of the noncirrhotic population that would be targeted for Phase III registration studies in NASH. We also believe a greater proportion of patients with F2 and F3 fibrosis in this study improves the chances of distinguishing the potential anti-fibrotic effects, a seladelpar in patients with NASH. We have also enrolled a significant number of patients, approximately 50% with diabetes, a population of NASH patients who are at increased risk for disease progression.

Going into the study, we wanted to enable that for all the needed decisions regarding commitment to Phase III development. This included enrolling a Phase III like population, including a complete dose ranging for appropriate dose selection and evaluating histological endpoint and outcome measures to confirm key aspects of seladelpar's mechanism of action. We believe that seladelpar has the potential to be a foundational therapy for NASH with actions that could potentially correct pathways involved in disease pathogenesis and progression. We believe that the ability of seladelpar to lower bile acids, cholesterol and other lipotoxic lipids in hepatocyte coupled with its anti-inflammatory and anti-fibrotic actions constitutes a promising profile. Furthermore, seladelpar lowers LDL cholesterol and triglycerides in obese hypercholesterolemic subjects, suggesting the potential for a CV benefit or avoiding the concerns about increasing CV risk that have been raised with other NASH candidate therapies. Sujal?

Sujal A. Shah -- President and Chief Executive Officer

Thanks, Chuck. Beyond our current focus in PBC and NASH, we continue to make progress with evaluating opportunities to expand the development of seladelpar for other chronic inflammatory liver diseases with high unmet need. This work includes discussions with thought leaders, evaluation of scientific and clinical rationale for development, assessment of the unmet need and other criteria important for us to determine future opportunities. We look forward to sharing updates on this front over the course of this year.

Turning briefly to our financials. Our cash, cash equivalents and marketable securities totaled $178.7 million at December 31, 2018. Based on current projections, our existing cash is expected to fund the current operating plan into 2021. For a detailed overview of our operating results for the 12-month period ending December 31, 2018, I will refer you to the press release and to our 10-K filed with the SEC today.

With that, I'd like to open up the call to questions. Operator?

Questions and Answers:

Operator

Thank you. We will now be conducting a question-and-answer session. (Operator Instructions) Thank you. Our first question comes from the line of Yasmeen Rahimi with ROTH Capital. Please proceed with your question.

Yasmeen Rahimi -- ROTH Capital Partners -- Analyst

Hi, team, thanks for taking my questions and congrats on the continued progress. Question one is, you had mentioned in the past of conducting a Phase III study, PBC study in hepatic impaired patients. Can you maybe give us an update where you are in that regard to maybe what are the gatekeeper? And then what caught our attention was also at the EASL preview was that you'll be presenting data on transplant survival at 52 weeks. So, can you give us a little bit color on that regard? Thank you.

Sujal A. Shah -- President and Chief Executive Officer

Yes, sure. Yasmeen thanks for the question. Maybe I'll address the first one and then I'll turn it over to Chuck and Pol to answer the second. I think ultimately, with respect to our PBC study...

Charles A. McWherter -- Senior Vice President and Chief Scientific Officer

Yeah, this is Chuck. So in terms of what's being presented at EASL this is work that's really led from a collaboration with Bettina Hansen and Gideon Hirschfield, you know that they've developed an overall GLOBE risk score. And so what was done was to really take baseline characteristics of patients who enrolled in the population and then evaluate what happens in the risk reduction using the GLOBE score analysis based on their end-treatment biochemical parameters. And I think gratifyingly what you see is what you would expect, we already know that the -- our cost reduction was linked to improve transplant free survival. This was underscored and reconfirmed by use of the most -- more sophisticated methodology using the GLOBE risk score.

Pol F. Boudes -- Chief Medical Officer

And then Yasmeen to swap and answer your first question, we recognize that there is a need in the broader PBC patient population, particularly in patients with advanced disease to have a better understanding of overall exposure and also have a better understanding of what the benefit risk profile is in that population. As you know, prior sponsor for medical oasis (ph). That's the population that was not included in their Phase III development, even though that population is in fact on their label and there is a desire. We continue to have conversations, particularly with the agency and thinking through the right study design for hepatic in patients with PBC in particular and understanding again not only exposure, but being able to actually measure what the overall benefit risk profile is in that population. So that's a dialogue that we continue to have with the regulatory agencies.

Yasmeen Rahimi -- ROTH Capital Partners -- Analyst

Thank you, team for taking my questions.

Pol F. Boudes -- Chief Medical Officer

Thank you.

Operator

The next question is from the line of Edward Nash with SunTrust Robinson Humphrey. Please proceed with your question.

Fang-Ke Huang -- SunTrust Robinson Humphrey -- Analyst

Hey, thank you for taking our question. This is Fang-Ke Huang on for Edward Nash. One quick question on your ongoing Phase II study in PBC. And can you talk about when you're going to present additional data this year? And my second question is on NASH. And given that we can ask you the data in second quarter, can you give us some your internal expectation in terms of what do you want to see in that trial? Thank you.

Sujal A. Shah -- President and Chief Executive Officer

Yeah, sure. Thanks for the question. So just to start off with respect to PBC and the ongoing Phase II study, as you know, we've had a series of presentations at recent medical meetings that, that study has progressed at sometime in the middle of this year in fact, this is a very robust ongoing Phase II study with north of 100 patients randomized. That entire population will be through the 52-week treatment period. And as has been our practice in the past, it's our goal to share that fulsome data set in peer-reviewed publications and at upcoming medical meetings and with all the patients coming through the study somewhere in the middle of the year this year that would be a dataset that we would expect to be able to share it at the end of this year or early next year.

Fulsome data set that ultimately will come in entire year before the data from in hand. So we think that's significant. To provide at least a little bit of an update by the way on this Phase II study, we continue to be very encouraged. This is a study now in which just over 60 patients in this study that has been through the 52-week treatment period and patients effectively eligible to roll into the long-term extension have all rolled in for the long-term extension. So we've got a significant number of patients now in this study for which we continue to collect safety and efficacy data beyond 52 weeks. So we continue to be extremely encouraged by the ongoing conduct of that study and perhaps I'll turn it to Chuck and Pol Boudes to talk a little bit about some of the thoughts with respect to NASH.

Charles A. McWherter -- Senior Vice President and Chief Scientific Officer

So I guess for us to the benchmark has recently reached results from similarly positioned Phase II dataset. So one thinks about medical data to certain extent, NGM data where the key issue is really the relative fat reduction. So for example NASH results was about 30%, net of placebo 40% overall. And the key characteristics that we look at is the relative fat reduction absolute fat reduction and importantly the proportion of patients who achieve a 30% reduction in fat. That's the key finding that has been increasingly been associated with histological improvement in NASH and linkage improvement in fibrosis as well. So for us we think maybe a clear sign of a competitive profile would be somewhere between 30% maybe down to 20% reduction in -- relative reduction in hepatic fat.

Fang-Ke Huang -- SunTrust Robinson Humphrey -- Analyst

Very helpful, thank you so much.

Charles A. McWherter -- Senior Vice President and Chief Scientific Officer

Thank you.

Operator

Our next question is from the line of Tyler Van Buren with Piper Jaffray. Please proceed with your question.

Tyler Van Buren -- Piper Jaffray -- Analyst

Good afternoon, guys and congratulations on the breakthrough designation. Just wanted to follow up on that a little bit in the release and on the call, you mentioned in order to get it, you need to see clinical evidence substantial improvement over existing therapies of at least one endpoint and imagine OCA is involved in that comparison analysis and you mentioned alkaline phosphatase in the release. But is there any back and forth on that with respect to other measures and results that have been presented and in particular maybe pruritus is curious to get thoughts there as it relates to the breakthrough designation?

Sujal A. Shah -- President and Chief Executive Officer

Yeah, absolutely, great question. So with respect to the package delivered to the agency when we applied for the breakthrough designation and I believe that's a tremendous accomplishment and a recognition now not only by the FDA, but with Prime designation by EMA that there is an opportunity certainly that we believe seladelpar can have a substantial improvement overall in treatment for patients with PBC. The designation is supported by the data that we submitted to the agency to date and that surround reductions in AP, the robustness of those reductions. And in particular, when you look at the proportion of patients thus far in our Phase II study that are experiencing normalization of AP, the latter is a key secondary endpoint in ENHANCE, it's something that we think is quite differentiated with the profile of seladelpar relative to other treatments available today.

Certainly, thus far, what we see around tolerability and the potential to see an improvement on pruritus that it will validate in ENHANCE, I think is an additional key upside potential differentiator with seladelpar relative to obeticholic acid. And that dataset that I think the agencies will continue to review, but important for them to review that in the setting of ENHANCE where we have handheld device looking specifically at JVH (ph) in that study with the validated PRO and we'll be able to provide information with the placebo compared or on that outcome.

Tyler Van Buren -- Piper Jaffray -- Analyst

Great. And the second question is with respect to the Phase II NASH results coming next quarter. Obviously, there's been a lot of focus on MRI-PDFF and reduction in fat and you guys just spoke about previously, and I think people are fairly well aware of how to think about potential anti-fibrotic effects and any sort of statistically significant result or medical result would be impressive there. But with respect to the other things that you mentioned in terms of bile acids and lipotoxic lipids and anti-inflammatory effects, how should we think about those in terms of analyzing the data that we will see, and specifically what types of reductions would be meaningful on the various endpoints related to those -- those measures?

Charles A. McWherter -- Senior Vice President and Chief Scientific Officer

Thanks, Tyler, this is Chuck. And so I think one thing that's really quite impressive in this study is the richness of the data that's going to be collected. We've already discussed what some of the endpoints and additional features will be but at top line as we anticipate sharing data, it will be the liver fat, I think transaminases or another feature that is really important and does have some literature (ph) that supports the correlation between transaminases and histological improvement.

I think another measure of the quality of population we enrolled is not just the NASH score but the baseline transaminases so ALT baseline had a mean of 61. AST was 46. So I think that'll be another point of interest to examine what potential treatment effects would be. In addition, as you mentioned we will collect a number of other wet biomarkers at 12 weeks. It will take us some time to work through those, and we just have a principal or a practice if you will, of releasing information when it's then appropriately cleaned, understood, analyzed and some of those features will take some time to work through as they're bad channelized. But you could anticipate that those would be part of a more fulsome data package that we would seek to present at a medical conference.

But all in all, I think the ability to look at liver fat transaminases, bile acid markers, wet biomarkers around fibrosis all linked together kind of connect some of our hypothesis and rationale about the mechanism of action of seladelpar really being foundational in terms of its effect on hepatocyte inflammation and fibrosis.

Tyler Van Buren -- Piper Jaffray -- Analyst

I just had a -- that's helpful. And I just sort of follow with respect to transaminase and ALTs. We've seen elevation in ALT is some of the other datasets for drugs that are reducing fat. What you think is causing it because to some extent with a higher proportion of reduction in fat? You're seeing a increased LTEs but then, there's also some debate as to whether it's related specifically to the mechanism. And if that's the cases, is there anything in particular with respect to seladelpar that you've seen pre-clinically, that would suggest that you won't see an increase in ALTs.

Charles A. McWherter -- Senior Vice President and Chief Scientific Officer

Well, in our study in mixed dyslipidemia, what we studied 50 and 100 milligram and little over 120 patients for 8 weeks. These are patients with baseline highly elevated LDL cholesterol and triglyceride obese subjects with presumptive fatty acid -- fatty liver disease. We didn't see any signal in transaminase. Tyler, I really can't help you much, I think that there is many mechanisms that lower lipids that I'm not aware that there is nothing in the label for statins, there's not really anything that I can point to PHR datas not necessarily the ones in development for NASH but early first generation compound certainly did have a signal if that mechanism linked, I would just be speculating that to be.

Pol F. Boudes -- Chief Medical Officer

Yeah, it's Pol, I think the PBC data are interesting because I think for us, we see the increase in transaminase as the signal is going inflammation in the liver. And we really have a very impressive decrease in transaminase that we've seen in PBC. So I think we are expecting to see that in NASH because the population is also population where you see the inflammation, which is linked with the transaminase. I think I was listening to Chuck now, I think I know what you're talking about and it's probably related to the PPAR-delta agonist. In fact there is one thing, and especially with the formula generation, I would say of PPAR-delta agonist. One thing that we know is that they are actually increasing -- this increases the bile acids in hepatocyte. And that could be one of the reason where in previous compound so an increase in transaminase. But I would say that for the other type of drug -- in general what you see is that these days and anti-inflammatory effect you see the decrease in transaminase.

Tyler Van Buren -- Piper Jaffray -- Analyst

Got it. Thanks for taking the questions.

Operator

The next question is from the line of Pasha Sarraf with SVB Leerink. Please proceed with your question.

Michael Giaquinto -- SVB Leerink -- Analyst

Yeah, hi everyone. This is Michael on for Pasha. Thanks for taking my question. So obviously still a couple of years away, but in terms of pricing dynamics between PBC and NASH, can you discuss that we should be thinking about your pricing strategy in a scenario in which you potentially have seladelpar approved for both the rare disease in PBC and NASH?

Sujal A. Shah -- President and Chief Executive Officer

Yeah, thanks for the question, Mike. It's still somewhat early for us. So it's hard to have a specific answer, but it certainly makes sense for me to be able to share with you some of the factors that we believe will be important as we put together some of the scenario planning that will do over the course of development for seladelpar not only in PBC, but also in NASH. Between now and 2021, at which point we expect to have ENHANCE completed. We're anticipating a number of different potential developments that will be inputs into our considerations. So first of all, with respect to the overall seladelpar profile we will learn from ENHANCE and hopefully validate and confirm the efficacy profile and alk phos reduction, the composite responder rate, as well as the normalization rates and effects on tolerability vis-a-vis pruritus.

These are key things that we continue to believe significantly differentiate seladelpar and validating what we've found thus far in ENHANCE will be a key input to thinking about the overall positioning even from a pricing dynamic perspective, with respect to seladelpar in PBC.

We will continue to look at the maturation of various strategies to also expand the addressable population. I think you're seeing today that there is a significant need for treatment for second-line treatment in PBC and with the potentially a better and more efficacious treatment, more better tolerated treatment and we think there's an opportunity to significantly expand that addressable population. That's another consideration that we'll put in as we think about the overall pricing dynamic.

Of course, all of that is -- will be reflective also of the overall competitive environment being how the current treatment continues to progress in the trajectory that we learned a bit about earlier today and how that continues to progress over the course of the couple of years. As well as its overall safety, tolerability patient retention on current treatment and how significant the pool of patients will be that are in need of a better tolerated treatment alternatives, as well as the more efficacious treatment alternative.

And finally just connecting it through I think really the root of your question with respect to how things develop in NASH. Not only for us, but I think it's important to recognize that the development of other agents in the NASH space will be another key input in terms of how we think about it. Fundamentally, with respect to PBC, the keys are the differentiated profile, the high unmet need in this population, and our ability to ultimately grow the overall population. We'll get there first, with respect to PBC and our goal is to be successful there, have a substantially improve treatment alternative that we think will underscore a key pharmacoeconomic benefit for that patient population.

As we progress in NASH we're successful in NASH of course there's still questions around what doses we believe we would carry forward post Phase II into Phase III development with seladelpar in NASH, so that's another key input and thinking about some of the differentiation between NASH and PBC. In the end, the profile and the data will also drive us to what the right positioning is for seladelpar in the NASH population. So if it's the more niche population that's -- I think that gives you some sense of where the pricing could come in based on what we see, not only in the effect of hepatic fat reduction, but of course, importantly an effect on NASH resolution and fibrosis. And if it's a broader population of course that's going to be reflective then of the pharmaco-economic benefit to address the broader population.

I've given you a lot of different inputs in the end. Our goal fundamentally is to be able to not only get these treatment through clinical development but also to support true patient full access and we'll take all of these things into account when we think about pricing differential.

Michael Giaquinto -- SVB Leerink -- Analyst

Thanks very much. Very helpful.

Operator

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

Jay Olson -- Oppenheimer & Co -- Analyst

Hey guys, congrats on all the progress. And thanks for taking my questions. You touched upon this earlier but with regards to the top line results from your Phase II NASH study. In addition to efficacy, I guess sort of expectation that you outlined for us. How much information can you provide around the safety and tolerability from that study and how specific can you be in the top line?

Sujal A. Shah -- President and Chief Executive Officer

Yeah, I think it's important to point out of course that this study progresses to 52 weeks with patients remaining blinded. So the measures we share at top line data will be group mean. So that we will expect and keep the blind for the patient population. Similarly, from a safety perspective, I think this is also very important for us to be able to be transparent report what we've seen from a topline perspective without jeopardizing the blind with respect to fundamental findings. But I can tell you is that I think it's important, at least today for me to tell you as we now have the study enrolled that we continue to be confident, this is a study in which medical monitoring is done on a daily basis as is typical for all clinical development and we continue to see support for executing the study as planned.

Jay Olson -- Oppenheimer & Co -- Analyst

Okay, great. Thank you. And then just I wanted to follow up on some comments you made earlier, with regards to work you're doing with thought leaders on additional studies to pursue for development of seladelpar and potentially broadening the population in PBC. Would you consider a first-line study in PBC?

Sujal A. Shah -- President and Chief Executive Officer

Well, I think, maybe I'll start off and perhaps Pol can add some color here as well. Fundamentally in PBC, the target is second-line treatment. UDCA is a generic treatment alternative, largely well tolerated for patients. A number of patients are in fact adequate responders to UDCA. And so really the key unmet need in the population of course are those that remain at risk of disease progression. There, we start to think a little bit about patients that are technically responders to UDCA, so experience an AP drop that brings them below 1.67 times upper limit of normal, but nevertheless remain elevated above the upper limit of normal.

And I think one potential alternative for seladelpar, as it continues to be an efficacious, well-tolerated and safe treatment alternatives through development, has the potential to expand into this patient population that we believe continues -- that would in fact benefit from a further reduction in AP, benefit from further anti-inflammatory measures from treatment alternative as well as even on some of the key clinical symptoms of the disease. So we think there's opportunities to expand the population even outside of thinking about the first-line therapy treatment alternative.

Jay Olson -- Oppenheimer & Co -- Analyst

Great. Thanks for taking the question.

Sujal A. Shah -- President and Chief Executive Officer

Thank you, Jay.

Operator

The next question comes from the line of Eli Merle with Cantor Fitzgerald. Please proceed with your question.

Eliana Merle -- Cantor Fitzgerald -- Analyst

Hey, guys. Thanks so much for taking my question. First, just in terms of, I guess mechanistically on NASH and clinical trial and I guess, what's your take on whether NASH resolution will be easier or harder to achieve clinically in F2 and F3 patients relative to an -- in F1 patients? I guess first off, generally for NASH agents, but also specifically in the context of PPAR-delta I guess, is there anything mechanistic that might drive greater activity in F3 and F2 patients versus F1?

Charles A. McWherter -- Senior Vice President and Chief Scientific Officer

Yeah, thank you for the question, Eli. This is Chuck. I think that what we saw is other sponsors have taken that kind of looking at fat reductions as a function of different degrees of that stage and haven't really seen any differences in response. I, may be somewhat simplistically I think about steatosis or fat, internal hepatocytes, liver injury, matrix is extracellular. I don't necessarily feel like those two things have a strong connection, if we drive fatty acid oxidation, which is basically pushing fat at a lipid droplets in the mitochondria, burning it, oxidizing it and breaking it down. I'm not sure that that would be different depending upon the extracellular matrix environment. So actually anticipate -- so the goal there is actually really to reduce not just fat, but ugly fat or bad fat. It's driving continuing tissue injury, which is causing inflammation and driving the fiber genesis. So I feel like the cost at stage, NASH resolution should be fairly neutral as at least a baseline assumption. Having said that, we all recognize that risk to progression, at least for liver complications, liver adverse events is strongly linked to that stage.

And so NASH resolution and the study even of more advanced disease where you're looking to ultimately resolve a degree of fibrosis with the potential benefit than long term and outcome, that is the setting where we would have a key interest. And I think that thought leaders that are focused there, at least as far as the liver is concerned, payers have likely going to have a focus there. And so that's the -- really the aspect in terms of liver effect. Of course, in terms of cardiovascular risk, let this in general decreasing them across the board irrespective of stage could have a potential CV benefit there as well. So that again would be in large measure, I think, independent of a hedge.

Eliana Merle -- Cantor Fitzgerald -- Analyst

Got it. That's very helpful. Thanks. And then just a quick question on PBC enrollment for the Phase III. I think you mentioned 150 trials. So, I guess if you could characterize, I guess, what proportion of the trial sites are already up and running versus the ones that need to still got to setup. Thanks.

Sujal A. Shah -- President and Chief Executive Officer

Yes, sure. Thanks, Ellie. We don't typically comment on mid-stage enrollment as well as how things continue to progress with respect to specific number of sites. I can tell you we initiated the study at the end of last year over 150 sites as you pointed out in over 20 countries across four continents. We've held all of our key investigator meetings across these different regions and thus the site continue to come on board and we continue to be very pleased with how things are progressing.

These are a challenge, largely because it's been orphan and rare disease and therefore we have what we believe to be a very robust global effort. And ultimately our most powerful tool, as we think not only about site initiation, but ultimately with respect to enrollment and completing enrollment are the strength of the Phase II data set that has been featured in key medical meetings across really all of the thought leaders globally in the space and in the field in PBC that's the support both from the FDA and the EMA with respect to breakthrough and Prime. These are the tools that we're able to leverage once these sites are opened to truly drive patients into our studies and continue to be very pleased with how things are progressing today.

Eliana Merle -- Cantor Fitzgerald -- Analyst

Got it, thanks.

Sujal A. Shah -- President and Chief Executive Officer

Thank you.

Operator

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

Steven Seedhouse -- Raymond James -- Analyst

Hi, good afternoon. Thank you. I had one clarification question regarding the protocol for reading biopsies in your Phase II NASH study. Our baseline and post-treatment biopsies for each patient paired and read together by the same pathologists or are all the biopsies scrambled together and then read i.e. not paired. Maybe if you could just describe that protocol a bit and are there any other ongoing or previous Phase II studies that used the similar protocol as the one you're using?

Pol F. Boudes -- Chief Medical Officer

Well, maybe I can. It's Pol. Maybe I can take the -- we haven't actually communicated on the details of the way we are reading the biopsy, but suffice it to say that we will use the best possible technology to win the biopsy. I can remind you also that we are using actually two pathologies that are extremely well known in the field that delivers pathology. And for us, we think it's the key criteria for having quite delivering of the biopsy.

NASH biopsies are not so easy to read activity. And I think we communicated months before and actually one of our radar is I recon that's done. Who is the -- I would say the inventor of the NASH, the scoring system. So we feel very confident that we have a very robust technology beyond that. So, so far everything moves very good.

Steven Seedhouse -- Raymond James -- Analyst

Okay. And just on the enrollment of these NASH trials. I mean most of these trials are enrolling more or less overlapping patient populations. You are obviously able to enroll your NASH study ahead of schedule. I'm just curious, is that more of a function of getting access to the right centers and the right trial lists? Or are patients actually educated about different mechanisms and playing a role in choosing which trials enrolling?

Pol F. Boudes -- Chief Medical Officer

I think it's a combination of factors, the one you're mentioning, is certainly a very important one. I think also when you go into these kind of six month campaigns, you want to really study what has been done before what worked well and what didn't work that well. So I think we are also working with somebody like Stephen Harrison, was really an amazing investigators who is extremely well organized and has a very efficient network of investigators. So I think also that's part of the work with Harrison (ph). The last thing, also is to be able to choose channel patients that are really the right patient that you want to enter in this study, and that's also the way to do that and I think again based on prior example is very proficient in this kind of a clinical trial.

Steven Seedhouse -- Raymond James -- Analyst

Thank you.

Operator

The next question comes from the line of Ed Arce with H.C. Wainwright, please proceed with your question.

Ed Arce -- H.C. Wainwrigh -- Analyst

A Sujal, Chuck, Paul, how are you. Thanks for taking my questions. And I'll add my congrats on the breakthrough therapy designation, that's the big one. So a couple of questions have already been asked, but I just wanted to drill a little bit further on your upcoming readout in the Phase II NASH study next quarter. So three here from me. First, if you could just discuss the considerations around the powering of that study in particular relative to key readouts like the 30% threshold on PDFF. Second is on the novel secondary endpoints that you've mentioned a few times, if you could just go over how those may support a more complete understanding of the compound in NASH?

And then the final question is, given this is a dose-ranging study of obviously the 10, 20 and 50 mgs, if you could just review how you decided on these three doses, I know we discussed this before, but just to go over that, and especially in terms of the prior data that you've seen. Thanks a lot.

Charles A. McWherter -- Senior Vice President and Chief Scientific Officer

Hi Ed, this is Chuck. I'm going to start out with the dose selection and the dose ranging. Just to remind you that in PBC, we've explored a very wide range of doses and in particular had settled on 10 milligrams in PBC is having a very effective treatment effect in particular call attention to the degree of alkaline phosphatase reductions, which we know from our prior work are linked with bile acids depression. So 10 milligrams with reductions and not only on phos, but also strong reductions in transaminases which is the shared each of the two diseases really helped us kind of the low end of the range per study.

At the top end we wanted to have a very wide range because if you really want to be able to select the dose if you decide to go forward, that's where many times in drug development folks trip themselves up. So at the top end, we had prior done a study in mixed dyslipidemia, the 120 subjects were treated for 8 weeks on 50 or 100 milligrams, these are subjects who are obese, have high LDL trig, have a lot of metabolic syndrome. And in that study, just to remind you, we saw a nearly 40% reduction in triglyceride, at almost 30% reductions in LDL cholesterol. And the treatment effects that were comparable between 50 and 100 milligrams. So 50 milligrams really seems like the -- it kind of the top end of the range to see an effect, the population that is, albeit, it's not NASH, it certainly share some of the features, the potential to see the risk reduction.

These are patients that one could think because of their body type are quite likely have a lot of fatty liver disease and the fact that the drug is safe and well tolerated, we didn't see a transaminase, signal 50 milligrams really kind of was at the top end and then 20 milligrams is that added just as kind of a log to increase over time to fill out the range.

Pol F. Boudes -- Chief Medical Officer

I think the other question was about the power of this study. So we've powered the study on the MRI-PDFF. As a reminder, the outcome is the relative change in fat fraction. And the study is actually very well powered because we have more than 80% power for difference of 20% and actually in this calculation, we also included the expected drop out rate so that's a power that's taking to account the potential drop out.

Ed Arce -- H.C. Wainwrigh -- Analyst

I'm sorry, please go ahead.

Sujal A. Shah -- President and Chief Executive Officer

I'm sorry, Ed, did we leave out any portion of your question? Was it on other additional biomarkers and measures in the study?

Ed Arce -- H.C. Wainwrigh -- Analyst

The sort of some of the novel secondary endpoints that you've mentioned already, previously. I just wanted to get maybe a little more details around how you're thinking of and there's a quite of number of them, but how are you ultimately once you've got the full 52-week data, how that will sort of fill out the entire package and help you decide on the Phase III design?

Sujal A. Shah -- President and Chief Executive Officer

Yes, that's a great question. So maybe I'll take a first tab and Pol can fill and if the -- to share additional thoughts on this. You're right, we have not only MRI-PDFF, we have MR Elastography. In addition, we'll have the liver multiparametric methodology for perspective where we can look at corrected T1 which is essentially a reflective of edema, which is linked to inflammation in the liver, inflammation in NASH. And then we'll have a number of biomarkers that have commonly been used in this stage process, we'll have bile acids before. In totality, a lot of different measures that ultimately, as I think you recognize, the histology is what matters, but what we are building is really a knowledge base, not only to help us make decisions.

So for example, we may see, at least theoretically, differences in different doses and different parameters. Fibrosis may have a -- you would look for example to see an effect that one dose on, say marker of fibrosis may be somewhat different than something you see for inflammation, maybe somewhat could line a little differently that you see in fat. And you put those all together with what we understand with respect to the kind of broad mechanism of seladelpar, that not may help us to understand.

Do we want it, just one dose for Phase III. If we are -- I mean, that the dataset that support that decision or do you want to have two or you want to have a focus more on fibrosis or do you want to make sure that NASH resolution is covered. So all of this really build data package that could help to plan for Phase III as well as, think about some of the characteristics of subsets of patients, the baseline patients who have a higher degree of fibrosis markers versus those that have lower or have higher bile acid responses versus those that have lower.

So it's a little, not just a little, it's highly speculative at this point, but as a scientist, I'm really excited about the rich dataset a distinct through its alternative scenarios, the hypotheses. So I don't know exactly how it'll turn out, but I know that we're very intrigued and would be quite committed to really take any kind of scientific view of the totality of the dataset that we get to help make some decisions around trade-offs that we might be facing.

Ed Arce -- H.C. Wainwrigh -- Analyst

Yeah, it seems very interesting, given that you're such a highly specific PPAR-delta. The data should mechanistically be very eliminating.

Sujal A. Shah -- President and Chief Executive Officer

Exactly.

Ed Arce -- H.C. Wainwrigh -- Analyst

Thank you so much.

Operator

The next question is from the line of Mayank Mamtani with B. Riley FBR. Please proceed with your question.

Mayank Mamtani -- B. Riley FBR -- Analyst

Hi, everyone. Thanks for taking my question and congrats on all the progress. My questions are generally are follow-ups to points already discussed. On PBC first, the breakthrough designation, like you pointed out, very strong Phase II data, the unmet need. But I was just curious how much a role that different mechanism, that seladelpar has, say, relative to bile acid analog play in that -- in the consideration with your view with the FDA. And then in PBC also I think you talked about a lot in the new indications or new potential markets that you could go. And could you also maybe talk about maybe combination as you -- as you are aware, many other mechanisms are also being pursued in Phase II studies. And then have a NASH follow-up. Thanks so much.

Sujal A. Shah -- President and Chief Executive Officer

Sure. Thanks for the question. So with respect to breakthrough the determination is not so much mechanism specific as it is evident to see the potential for substantial improvement in overall profile and overall benefit. So I think fundamentally the agency as we've seen in our Phase II development concur that the robust nature of the alkaline phosphatase drop, the proportion of patients not only experiencing decreases below 1.67 times upper limit of normal but also into the normal range was quite significant and differentiated from Ocaliva. So it was more with respect to the actual treatment effect than anything determined with respect to just being a different mechanism.

I'll highlight that seladelpar is really the only compound that has breakthrough designation as well as prime for PBC today. Maybe what I'll do is, I think your other question was I think addressing how we think about combinations. And I think there in particular in the setting of NASH while we're very focused on completing this Phase IIb study and understand the overall profile of seladelpar which we've long since discussed, we believe could be a potential foundational treatment alternative given its impacts on the metabolic elements as well as the inflammatory and fibrotic nature of the disease.

We -- I think in Chuck's group, we have been thinking a bit more about combinations with seladelpar particularly in that setting. Maybe I'll turn it over to Chuck to talk a little bit about some of that work.

Charles A. McWherter -- Senior Vice President and Chief Scientific Officer

Yeah, so we've been -- kind of our focus is been trying to understand the scientific rationale where mechanism could either enhance or reenforce actions against various features of this disease or might fill in a gap. So, we've been focusing recently on selecting lead molecule fleet therapies that have either metabolic, anti-inflammatory or anti-fibrotic activities and have been studying those in obese, mouse models of NASH or you can look at characteristics of various biochemical features, both in the liver and in plasma as well as NASH pathology and fibrosis. And we presented some of these, for example, at the Liver Meeting, we had a presentation at NASH tag and at the Keystone meeting and we should have a -- we will have an additional presentation coming up at EASL where we look at these agents both alone. So benchmarking and in combination in that context, I think that we've had some really interesting observations for example and the study that we did. Looking at liraglutide, the GLP-1 receptor agonist, which also has some human NASH data, have some effects on NASH pathology.

Comparing that mechanism and looking at in a combination, we found that those two really worked well together, both in terms of the effect on weight loss, fat reduction, NASH pathology. But interestingly, there where liraglutide in this mouse model had very minimal effect on fibrosis. Seladelpar was able to add to all of the components and then fill in the gap if you will, added anti-fiber genesis compound into the mix. So as one begins to think about combination therapy, think that's a strong rationale, let's say, combinations with marketed drugs that have the potential to be redirected to NASH, where you can have some added aspect, but at the same time add something that's not available with the other agents.

We've continued to do that, that some of the presentations that you'll see at EASL. And we continue even to the state to look at compounds that are in late stage development as well as marketed drugs that have the potential to be either metabolic, anti-inflammatory or anti-fibrotic or some combination of those two.

Mayank Mamtani -- B. Riley FBR -- Analyst

Great. That's super helpful, thank you. And then on NASH, I'm also thinking about the sites. Is there any overlap in the PBC? And again, different patient populations, but is there any overlap that you see in the NASH in the PBC sites? And specifically for NASH, are there international studies also part of the program may be I missed that, maybe you had mentioned it before, there's generally the baseline, there have been different placebo responses in the US versus international. So just thinking through how to think about the placebo response there?

Pol F. Boudes -- Chief Medical Officer

So, I can take the first part of the question. So there is some overlap between PBC study and NASH study, it's not the big overlap actually, people tend to be more specialized into rare disease or into NASH study. So, but there is a little bit of an overlap.

Charles A. McWherter -- Senior Vice President and Chief Scientific Officer

I think the placebo response question, I think of course is a very genuine question, there's been entire conferences or at least major portions of conferences trying to address that issue, KOLs, sponsors and regulators are keenly aware of that and you can see podium presentation showing the range of placebo responses. I think in our case the practicality is that we selected US sites only in our study. This is really a syndicate of sites that have lot of experience in NASH and were able to leverage. I really very, I think thoughtful and effective strategy to be efficient to enroll the kind of population that you would like to have in Phase III.

And then coming to your question around placebo response, I think that's in our favor is just a very high proportion of subjects with high NASH, our mean was 5.2, a high degree of inflammation so baselines is 61 and 46 in ALT and AST respectively. And I think importantly, the proportion of patients with F2 and F3, baseline fibrosis. And the latter in particular, I think gives some reassurance around, let's put it this way less likely to see a placebo effect, it's a little bit easier to imagine. And I think there's some data that's say a little bit easier for an F1 to kind of move back and forth between F1 and F0. Whereas having more advanced fibrosis is not something that would necessarily be a subject to the degrees (ph) of a leader different or the time variation theoretically, it could be less so than in the earlier stage fibrosis.

So I think you know in terms of the practicality of a study of its size and speed of which and the quality that is vital to us. I think we've done just about every reasonable measure, we can to try to minimize any potential placebo effect.

Mayank Mamtani -- B. Riley FBR -- Analyst

Sounds, great. Thank you, guys. Appreciate it.

Sujal A. Shah -- President and Chief Executive Officer

Thank you.

Operator

The next question is from the line of Patrick Dolezal with LifeSci. Please proceed with your question.

Patrick Dolezal -- LifeSci Capital -- Analyst

Hi. Just one for me. Can you just speak to the potential of seladelpar in diabetic versus non-diabetic NASH patients and provide guidance on whether you plan to analyze data from these population separately.

Charles A. McWherter -- Senior Vice President and Chief Scientific Officer

Yeah, of course, the overall top line results will look at the entirety of the population. This particular aspect, I'm a little uncomfortable speculating or handicapping what we might see. But we certainly would examine various subsets of population with respect to the baseline parameters. The -- importantly, I think because diabetes is the risk factor that known to be associated with higher risk of progression of NASH, we did stratify for diabetes as a baseline component. And I think also because it's such an important comorbidity, and some drugs that I alluded to earlier, that may have a place ultimately in the treatment of NASH are in fact registered as anti-diabetic medications.

I think that examining that makes makes a lot of sense. So having about half of our patients being tied back in a study of this size at least will give us some insight to think about, are there any differences and say, a sensitivity analysis among various parameters, including the potential for effects on glycemic parameters, it's certainly something that would of course you'd expect us to take a look at. What that ends up happening to BI, Patrick, I really -- I'm really not sure.

Does that shape our strategy for Phase III, does that push us one way or another in terms of potential ultimate type of population, we would target if we ultimately successful, it's early to say. But as you would expect, we always take the position that we should be informed by the data. And so we've at least -- we've at least made sure that we can collect the data.

Patrick Dolezal -- LifeSci Capital -- Analyst

Great, thank you.

Charles A. McWherter -- Senior Vice President and Chief Scientific Officer

Thank you, Patrick.

Operator

Thank you. At this time, I will turn the floor back to management for closing remarks.

Sujal A. Shah -- President and Chief Executive Officer

Well, thank you all once again for joining us today. We are extremely passionate here at the company about the work that we have and opportunity to do with patients, their caregivers really world-renowned thought leaders in the space. We continue to remain focused on our core objective to bring seladelpar to patients. In PBC, we firmly believe that we have an opportunity to substantially improve treatment for patients. We're certainly heartened to see that with the granting of the breakthrough designation as well as previously Prime, that both the FDA and EMA see this potential for seladelpar as well.

And NASH, we are excited to be quickly approaching a dataset that we believe has the potential to support the positioning of seladelpar truly as a foundational treatment alternative for patients with this disease. And particularly given seladelpar's unique mechanism of action, we fundamentally believe there isn't a more compelling compound being studied today. We look forward to providing updates on these programs and plans to expand the development of seladelpar in the coming year. Thank you.

Operator

This concludes today's conference. You may disconnect your lines at this time. Thank you for your participation.

Duration: 69 minutes

Call participants:

Daniel Menold -- Vice President of Finance

Sujal A. Shah -- President and Chief Executive Officer

Pol F. Boudes -- Chief Medical Officer

Charles A. McWherter -- Senior Vice President and Chief Scientific Officer

Yasmeen Rahimi -- ROTH Capital Partners -- Analyst

Fang-Ke Huang -- SunTrust Robinson Humphrey -- Analyst

Tyler Van Buren -- Piper Jaffray -- Analyst

Michael Giaquinto -- SVB Leerink -- Analyst

Jay Olson -- Oppenheimer & Co -- Analyst

Eliana Merle -- Cantor Fitzgerald -- Analyst

Steven Seedhouse -- Raymond James -- Analyst

Ed Arce -- H.C. Wainwrigh -- Analyst

Mayank Mamtani -- B. Riley FBR -- Analyst

Patrick Dolezal -- LifeSci Capital -- Analyst

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