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CymaBay Therapeutics Inc (CBAY 0.03%)
Q4Â 2019 Earnings Call
Mar 12, 2020, 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 Full-Year 2019 Financial Results and Business Update Conference Call. At this time, all participants are in 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.
Dan Menold -- Vice President, Finance
Thank you, operator. And good afternoon, everyone. I hope that you've had a chance to review the press release we issued announcing our fourth quarter and full-year 2019 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. We will provide an update on the review of our clinical programs, upcoming milestones, assessment of strategic pathways and financial position before we open the call for Q&A.
Before we begin, I'd like to remind everyone that statements made during this conference call, including the Q&A session, relating to CymaBay's expected future performance, business prospects, events or plans, including clinical plans 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 -- President and Chief Executive Officer
Good afternoon. And thank you for joining us. Since we announced the decision to halt development of seladelpar last November, we have been focused on two parallel initiatives, an investigation of the unexpected histologic findings identified by the study pathologist in the Phase 2b study of seladelpar in NASH and an evaluation of potential strategic alternatives for the company.
Before I step through our progress with these activities, let me briefly review the events leading up to November's decision to halt seladelpar development. In 2018, we initiated a randomized, double-blind, placebo-controlled, dose-ranging Phase 2b study of seladelpar, which enrolled 181 patients with biopsy-confirmed NASH.
The primary efficacy outcome was the change from baseline in liver fat content at 12 weeks and key secondary measures included evaluation of histological improvement in NASH and fibrosis, as assessed by comparing liver biopsies taken at baseline in 52 weeks.
In June 2019, we reported minimal reductions in liver fat, but robust and clinically meaningful reductions in markers of liver inflammation and injury, including ALT, AST, gamma GT and alkaline phosphatase at 12 weeks. As the majority of patients in the study had completed 52 weeks of treatment by last November, the study pathologists began their blinded assessment of the week 52 liver biopsies, and the plan had been for them to conclude the biopsy review for those remaining patients who were finishing their 52 weeks of treatment sometime in February of this year.
As they read the first batch of slides, they identified a subset of patients with an unexpected pattern of histological findings overlaid on NASH pathology. These findings, which they described to us as unexpected and NASH pathology, were predominantly characterized as an interface hepatitis with or without bile duct injury. Despite these observations, patients enrolled in the study, including those identified by the pathologist as having unexpected histologic findings, had either improving or stable levels of biochemical markers of inflammation and liver injury throughout the 52 weeks of treatment, which included ALT, AST, gamma GT, alkaline phosphatase, total bilirubin, direct bilirubin, and high sensitivity CRP.
In addition, there were no signals of immune or allergic reaction as reflected by changes in the eosinophils or in clinical symptoms of liver injury, nor were there other changes in markers that can be associated with progressing liver disease, such as platelets or coagulation parameters. No occurrences of liver decompensation or liver-related AEs were observed for any of these patients. Importantly, these findings were unanticipated based on our prior clinical and pre-clinical experience with seladelpar.
After consulting with expert liver pathologists and hepatologists and with patient safety at the forefront of our mind, the decision was made to halt development of seladelpar in all indications, while committing to an in-depth review of these findings. The FDA agreed with this decision, while formally placing a clinical hold on seladelpar development and subsequently provided input on our plans to further investigate the situation. Our investigation includes three activities intended to confirm and subsequently understand the significance of the findings identified by our study pathologists.
The first is a comprehensive collection and review of data, including patient demographics, medical history, concomitant medications and a broad set of biochemical markers typically elevated in drug-induced liver injury. The second is a blinded, independent review of both baseline and end of treatment biopsies by several world-renowned liver pathologists.
And finally, the third is a formal pathology and clinical hepatology review panel meeting that we are looking to convene in the middle of the second quarter; during which, experts will review all information gathered to provide an independent consensus determination of the role of seladelpar in these findings. These steps will be essential for us to understand the nature and significance of the findings and to have the requisite follow-up dialog with the FDA.
After completing our investigation, we plan to try to meet with the FDA before the end of the second quarter to discuss potential future plans for seladelpar.
Let me ask Chuck to provide you with some further updates. Chuck?
Charles McWherter -- Senior Vice President and Chief Scientific Officer
Thank you, Sujal. Our decisions last November were based on a review of the first 86 end-of-treatment liver biopsies read by our study pathologist. Since then, the review has been completed for all 152 patients with end-of-treatment biopsies. Across subjects with or without these unexpected histological findings, all of the standard laboratory markers usually associated with drug-induced liver injury, including allergic and autoimmune reactions, either improved or were stable. This encompasses liver tests, including ALT, AST, gamma GT, alkaline phosphatase and total bilirubin. Again, all independent of whether or not there were unexpected findings. Further, patients with unexpected findings did not display any pattern of clinical symptoms, medical findings or liver-related adverse events.
The liver tests at 52 weeks, there were 19, 35, 41 and 40 evaluable patients in the placebo, 10, 20 and 50 milligrams seladelpar groups respectively. The corresponding percent reductions from baseline at week 52 in ALT were plus 1.1%, minus 29.1%, minus 41.9%, and minus 41.3% respectively. Similarly, for AST, relative reductions at week 52 were minus 0.5%, minus 19.7%, minus 25%, and minus 16.6% for placebo, 10, 20 and 50 milligrams seladelpar. Finally, corresponding decreases in gamma GT were minus 0.6%, minus 29%, minus 46.1% and minus 35% for these groups respectively,
The effects at week 52 in the parameters I mentioned, as well as in alkaline phosphatase and total bilirubin resemble the results we reported at week 12 last June. We have also begun to analyze additional biomarkers. And today, we have yet to see any changes on treatment that might explain the histology identified by our study pathologist.
The completion of the end-of-treatment review allows us now to share the key secondary histological endpoints in the study. The two most important endpoints are those that have been used as Phase 3 endpoints, namely the proportion of responders in each treatment group having either, one, NASH resolution defined by a ballooning score of zero and a lobular inflammation score of zero or one with no worsening of fibrosis stage; or two, the improvement of fibrosis by one or more stage with no worsening in NASH.
Out of 181 patients enrolled in the study, there were 152 patients with paired biopsies at entry and end of treatment. I'll remind you that the study randomized subjects into four treatment groups of 10, 20 and 50 milligrams seladelpar and placebo in a two to two to two to one ratio. The number of patients with paired biopsies in the placebo, 10, 20 and 50 milligrams seladelpar groups were 25, 39, 42 and 46 respectively. The percent responders with resolution of NASH with no worsening in fibrosis were 8%, 10.3%, 19% and 26.1% in the placebo, 10, 20 and 50 milligrams seladelpar groups respectively. The corresponding rates for at least a one stage or more improvement in fibrosis with no worsening in NASH were 20%, 23.1%, 23.8% and 37%. The percentages of patients meeting both endpoints were 8%, 5.1%, 11.9% and 19.6% for the placebo, 10, 20 and 50 milligrams seladelpar groups.
We believe the completion of the additional biomarker analysis in parallel with the ongoing blinded and independent reviews of liver biopsies will provide a detailed picture of our patient population in this study. The independent pathology review will include an accepted pathology scoring framework, known as the Ishak Modified HAI scoring system, to quantitatively characterize features of histology present in our patient population, both at baseline and end-of-treatment.
Among these features includes the scoring for the presence and severity of interface hepatitis, which is not quantified in the existing framework for scoring NASH pathology. The entire clinical picture of our patient population at baseline and end-of-treatment will be central to the expert panel review we look forward to convening in the second quarter, and which outcome we believe will allow for properly informed dialog with FDA regarding seladelpar development.
Now, let me turn it back to Sujal.
Sujal Shah -- President and Chief Executive Officer
Thank you, Chuck. The elements of our investigative analysis have been discussed with the FDA. Based on what we have learned to-date, we believe it is not only prudent, but that we have an obligation to see this process through to its completion on behalf of all our stakeholders, including patients, regulators, and our shareholders.
I'll remind you that in addition to the data we have shared with you today from our study of seladelpar in NASH, we have presented seladelpar's Phase 2 data in PBC patients at major medical meetings over the past few years, highlighting its efficacy, safety and tolerability in this patient population. In parallel to our investigative activities, we have been focused on a comprehensive evaluation of all strategic alternatives to maximize shareholder value, including a liquidation, a sale, a merger, asset acquisitions or potentially continuing clinical development of seladelpar based on additional discussions with the FDA.
While we remain committed to completing the investigation, we believe this evaluation is prudent in order to make decisions expeditiously once we gain clarity on the potential path forward for seladelpar. In other words, we are keeping all potential doors open at this stage. Since our announcement last November, we have also been focused on a series of cost-cutting measures to minimize expenses and conserve capital.
I'll turn it over to Dan to provide you with an overview of our actions and review fourth quarter and full-year 2019 financials. Dan?
Dan Menold -- Vice President, Finance
Thank you, Sujal. Following the decision to place the seladelpar program on hold, management implemented a cost containment and restructuring program during the fourth quarter in order to reduce our operating expenses and associated cash burn. Specifically, we froze hiring, significantly scaled back future procurement plans, reduced our workforce by more than 60% and scaled down or canceled many of our existing contracts for goods and services. As a result of these actions, we recorded a $5.1 million restructuring charge during the fourth quarter, which includes $2.9 million of employee severance costs, $0.9 million of non-cash stock-based compensation expense associated with the acceleration of stock options of certain terminated employees, and $1.3 million of charges associated with the termination of certain contract manufacturing agreements.
Of the total $5.1 million in restructuring charges, $3.3 million of these charges are expected to be settled in cash. We paid out $0.1 million in Q4 and the remainder is expected to be paid out over the course of fiscal 2020.
I will now briefly turn to a review of other elements of our Q4 and full-year financial results. Research and development expense for the three and 12 months ended December 31st, 2019 was $20.9 million and $83.8 million respectively. This compared to R&D expense of $16.4 million and $58.1 million for the same periods in 2018. Prior to the decision to halt development of seladelpar in November 2019, research and development expense for the three and 12 months ended December 31st, 2019 was $20.9 million and $83.8 million respectively. This compared to R&D expense of $16.4 million and $58.1 million for the same periods in 2018.
Prior to the decision to halt development of seladelpar in November 2019, research and development expense in the fourth quarter and 12 months ended 2019 was generally higher than in 2018 due to expanding clinical trial activities related to our PBC Phase 3 clinical trial, our PSC Phase 2 clinical trial and other NDA-enabling studies.
General and administrative expense for the three and 12 months ended December 31st, 2019 was $4.5 million and $19.2 million, respectively, compared to $4.2 million and $14.4 million for the same periods in 2018. Prior to the decision to halt development of seladelpar, G&A expense in the fourth quarter and 12 months ended 2019 was higher than in 2018 as a result of higher labor costs and other administrative expenses necessary to support our expanding development activities.
Overall, our net loss for the three and 12 months ended December 31st, 2019 was $29.4 million or $0.43 per diluted share and $102.8 million or $1.53 per diluted share, respectively. This compares to net loss of $19.4 million or $0.32 per diluted share and $72.5 million or $1.26 per diluted share for the three and 12 months ended December 31st, 2018. The increase in net loss for the fourth quarter and full-year 2019 compared to the prior year periods was primarily due to increases in our operating expenses, including our restructuring charges, as discussed earlier.
Finally, I'd like to share with you our current cash position, the outlook for planned activities in 2020, and the expected impact of those activities on our operating expenses and our cash burn. At December 31st, 2019, we had $190.9 million in cash, cash equivalents and short-term investments on hand compared to $178.7 million at December 31st, 2018.
As noted earlier, in 2020, management intends to focus on concluding its investigation of the clinical observations seen in NASH patients and completing a review of strategic options. In addition, management will work to complete ongoing clinical study closeout and monitoring activities. These activities involve a number of key efforts, including caring for and monitoring NASH patients with histologic observations, recovering investigational drug product, conducting early termination visits with patients, performing investigator site monitoring and closeout visits and quality reviewing, analyzing and reporting on clinical trial data accumulated to-date.
Consistent with amounts previously provided in our recent letter to our shareholders, we continue to estimate our overall cash burn will be between $30 million and $50 million for the first half of 2020. Of this total, we expect between $20 million and $35 million will be used to fund the clinical study closeout, patient monitoring and seladelpar investigation activities previously mentioned.
Let me now turn the call back to Sujal for final remarks. Sujal?
Sujal Shah -- President and Chief Executive Officer
Thank you, Dan. I hope this update has been helpful. I want to reiterate that we believe we are engaged in the most sensible and reasonable path forward at this time. There is still much to be learned in the first half of this year in our ongoing investigation that we believe will provide clarity on the situation and potential path forward. The best course of action, given what we know about seladelpar, is to continue to evaluate our clinical findings, while also, in parallel, ensuring that we are thoroughly assessing strategic alternatives.
While in our view, it is too soon to commit to any specific strategic option, we will certainly not be caught unprepared in the event this emerges as the best way to maximize shareholder value. Before opening up the call for questions, I'd like to remind everyone that the purpose of today's call has been to provide updates on our corporate activities and our fourth quarter and full-year financial results. In order to ensure the ongoing investigation involving blinded independent reviews of patient biopsies is not influenced in any way, we will be limited with what we can share in detail on this activity beyond what we have discussed thus far today.
Operator?
Questions and Answers:
Operator
Thank you. [Operator Instructions] Our first question comes from Yasmeen Rahimi of ROTH Capital Partners.
Yasmeen Rahimi -- ROTH Capital Partners -- Analyst
Hi, Chuck. Hi, Sujal. Thank you for the additional color. Just two quick questions for you. The first one is, are you able to give us a little bit more color in regards to the numbers of these atypical lesions between placebo and seladelpar, between placebo and treatment arms at the beginning and at the end of the treatment? Can you give us a score? Or if you can't give that, can you just walk us through exactly how initially the biopsy samples are read? Did the pathologists have a second reading at end of treatment, basically where the baseline sample is reread at the time. So, just kind of the logistics of how all that occurs could be very helpful for us. Thank you.
Sujal Shah -- President and Chief Executive Officer
Yes, thank you for the question, Yasmeen. I can highlight some of these details and certainly ask Chuck to jump in with anything that I missed. You're absolutely correct. At some point in time, we will share all the details with respect to the incidence of these unexpected findings at end-of-treatment. But as I mentioned earlier, I think part of the key for us is to get through an independent blinded assessment of both baseline and end-of-treatment biopsies by several well-known and world-renowned pathologists with a tremendous amount of experience in NASH to confirm as well as ultimately have some interpretation as to the significance of these findings. So, we won't share them just yet until we get through that investigation. We think it's incredibly important for us to maintain the integrity of that element of the investigation, particularly as we take it to the panel review and ultimately to the agency. With respect to the NASH biopsy reading, we had a single pathologist do all the screening biopsy read, and we had that same pathologist and a second, both well-known and experienced pathologists in NASH, read the end-of-treatment biopsy.
At this point in time, we've not had those specific pathologists reread any of either the end-of-treatment or baseline biopsies. That is, in particular, the key activity being conducted by several independent pathologists at this point in time.
Yasmeen Rahimi -- ROTH Capital Partners -- Analyst
Thank you, Sujal, for the color. That's helpful. Are you -- I mean I'm certain there are only a handful of very well-known pathologists. Are you comfortable to share with us how many total pathologists are part of this consortium of rereading and looking at the samples?
Sujal Shah -- President and Chief Executive Officer
Yes. Again here, we have several folks that we'll mention once this is actually completed. I think, again, in the interest of maintaining their independent review, we'd prefer to do so as we share results of their analysis, which we will of course do. I think, as we mentioned -- as I mentioned in the prepared remarks, our plan is to, in fact, have this review completed and conduct a panel review meeting with these expert pathologists along with our study pathologists and clinical experts in the same room effectively to have some interpretation of the results of the investigation sometime in the middle of the second quarter, with the goal of ultimately taking that interpretation and the results and any conclusions back to the agency before the end of Q2. So, we'll do that, Yasmeen. But, again, I think it's really important for us to just let those individuals get through their independent review.
Yasmeen Rahimi -- ROTH Capital Partners -- Analyst
Thank you and best of luck as you guys are digging deeper into this.
Sujal Shah -- President and Chief Executive Officer
Thank you.
Operator
Our next question comes from Eli Merle of Cantor Fitzgerald.
Eliana Merle -- Cantor Fitzgerald & Co. -- Analyst
Hey, guys. Thanks so much for taking the question. I guess in terms of the range of outcomes from this independent investigation, could you sort of walk us sort of the range of scenarios? And then, in terms of potential future next steps for seladelpar, you mentioned that you plan to meet with the FDA and discuss it. I guess, how do the findings you've seen so far maybe impact or shape how you're looking at what indications you would be discussing this in and if it's different sort of -- [Indecipherable] about the role that could potentially be different in each indication. And then, I guess, just in terms of -- you're obviously digging incredibly deep into this data. Just, I guess, what have you maybe uncovered so far as you dig into these safety events that might have given you more comfort sort of around the safety profile? Thanks.
Charles McWherter -- Senior Vice President and Chief Scientific Officer
Yeah. Thanks, Eli. This is Chuck. I think you're probably going to hear a recurrent theme here, as I think -- but just to give you a sense, the way that we're approaching this as a completely independent, arm's length, expert panel review that includes not only the hepatopathologists, but experts in drug-induced liver injury, experts in clinical hepatology, including NASH, as well as cholestatic liver disease since we've been developing seladelpar there as well, other regulatory experts and then participation by individuals, who've been involved in the study. But the panel itself will be individuals who have had not any association with the company or with the study. It'll be completely arm's length. It will be -- there'll be minutes. There'll be questions that will be posed to the panel. And we think it's vital that whatever we determined can really help inform the agency and regulatory decisions. So, in light of that, I don't think that I really want to speak to the range of options. I think everything is possible.
We do feel that if the determination of the panel, if they make a consensus view that it's appropriate to consider based upon their causality and risk for hepatotoxicity that seladelpar could be contemplated for development, that'll be their recommendation. If on the other hand, they have concerns that'll be shared with the agency as well. We think that kind of taking this very rigorous, science-based independent review is the level that would be required for the agency to make a really strong and comfortable decision if that's what happens for seladelpar to move forward.
So in that light, I don't think I want to comment really on any specifics about how this might play out. I think that for those on the call, I think what you can take comfort in is just the commitment to the quality, the integrity, thoroughness, so that when the results are made available, it's, we feel, the best that could be done. And I think that's appropriate for patients, people who've invested in the study, investigators, regulators as well, and, of course, importantly, our shareholders that we ultimately hold responsibility to because this is where the most value we created for them.
Sujal Shah -- President and Chief Executive Officer
And, Eli, maybe I'll just add, as you asked a bit of a question around our level of confidence. I think Chuck expressed it well. We're still in the midst of this investigation. But as we discussed today, as we've collected additional biomarkers that are typically elevated when you see drug-induced liver injury, the fact that we've not yet seen any specific signal across a host of biochemical markers, not just those we reported back in November, but additional biomarkers that have been collected and continue to be collected, it really guides us to making sure that we have a fulsome understanding of the patient population in our study, not just at end of treatment, but also at baseline. We shared effects on histology endpoints today as well. I think some of what we hypothesized around the anti-inflammatory benefits of seladelpar have translated to the histology endpoints we reported today. So, the robust decreases in liver enzymes, ALT, AST, gamma GT and alkaline phosphatase that we've seen at 12 weeks have been maintained through 52 weeks. And with respect to at least improvements in fibrosis without worsening of NASH, and NASH resolution without worsening of fibrosis, I think we see, again, these key effects of seladelpar translating into benefits on histology for a portion of patients. So, it's a complete picture of what we continue to learn that really focuses us in on making sure that we complete this investigation in its entirety and maintain an integrity and independence of that investigation at the same time.
Eliana Merle -- Cantor Fitzgerald & Co. -- Analyst
Thanks so much for the color.
Operator
Our next question comes from Steve Seedhouse of Raymond James.
Steve Seedhouse -- Raymond James Financial Inc. -- Analyst
Thank you. Thanks. Thank you guys for reporting the data from the end-of-treatment histology assessment. I just want to commend you for continuing to look into the results and share those with the community. I thought it was remarkable to see that the NASH endpoints, as you just mentioned, fibrosis and NASH resolution had a dose response signal after all, which obviously is correlated with the liver enzyme changes and inversely correlated with liver fat.
So, I had a few questions. I'll try to keep it to one and hopefully wouldn't compromise the ongoing blinded investigation. And the first one is just how are the patients doing that had the interface hepatitis? Have there been any clinical correlates or problems for these patients subsequent to the finding?
Sujal Shah -- President and Chief Executive Officer
Yeah. So, thanks for the question. To-date, there haven't been any further complications reported. Of course, we remain engaged with investigators and we have in place plans and a protocol to continue to follow patients. We do have a recommendation for a repeat biopsy for those subjects in particular who had findings that would occur six months after the last dose of the drug. And so, that process remains ongoing. I don't have anything to report now. It's just -- it's still in progress. But, to-date, no news is good news, I would say.
Steve Seedhouse -- Raymond James Financial Inc. -- Analyst
Okay, thank you. And do you have an opinion yet on if the finding is mechanism specific, i.e. related to PPAR-delta or molecule specific, i.e. something that you could remove from the pharmacology by improving the molecule, but retaining what looks to be efficacy?
Sujal Shah -- President and Chief Executive Officer
Well, I think the whole point of the independent review is just to figure out what did happen. So, I think I don't want to go to the next step about what was the cause until we understand what was caused. So, I'm just going to defer an answer to that. I will mention that in all of our preclinical work in multiple obese mouse NASH models, we hadn't seen any findings like this. So, the mechanism of itself is still not, in our mind, my mind anyway, yet linked. So, we'll just have to wait until the independent review is completed and then I think that will be appropriate for the panel to make any comments or recommendations to us on an additional follow-up.
Steve Seedhouse -- Raymond James Financial Inc. -- Analyst
Okay. Maybe I'll phrase this next one a little bit differently. Are you able to -- given the design of the study, are you able to exclude the possibility that this could be a drug-drug interaction that's causing this signal? Or is that one possibility that could be concluded from the investigation?
Sujal Shah -- President and Chief Executive Officer
Well, I think if you come back to some of the remarks we've made at this point in time as we look at things like medical history, concomitant medication, other underlying conditions, we've yet to see any pattern, in fact, of these factors related to patients with unexpected findings at end of treatment. So, again, where we are today is in a position where this independent review specifically will shed the most light around any significance with respect to these findings, any potential causality, but also provide a much more in-depth picture around the specific unexpected findings at end of treatment, given the fact that this independent review will include scoring systems that are used -- that are not part of a typical NASH scoring system. So, as Chuck mentioned, the Ishak Modified Histology Activity Index, or HAI, has several different components that are scored and quantified, including features such as interface hepatitis, hepatocellular necrosis, number of different things that are not typically quantified, if you will, in NASH other than called out to the degree that a study pathologist sees something unusual or untoward. So I think the in-depth methodology and framework that we're using here with respect to the pathologist involved in the investigation is one in which will give us a tremendous amount of additional information with respect to our study population.
Steve Seedhouse -- Raymond James Financial Inc. -- Analyst
Okay, thank you. Last one for me. I find it hard to believe that you would observe this -- like this is a NASH-specific finding, but maybe there is -- obviously, the investigation will uncover that. You've obviously treated a lot of PBC patients with this drug. So, can you just remind us, have you ever during the development of seladelpar in PBC assessed biopsies in those patients post treatment? And if so, can you quantify that, how many biopsies?
Sujal Shah -- President and Chief Executive Officer
Yes, sure. Maybe I can answer the question. So, as we discussed in the past, biopsy is not part of medical practice in PBC. It's not necessary, in fact, to diagnose the disease. It's not part of clinical studies, either. In our enhanced Phase 3 study, we did offer patients the opportunity to volunteer to have a baseline biopsy. The intention in that study would have been that at some subsequent time point, as patients rolled into a long-term extension, we would have the opportunity to take a second biopsy perhaps that, for example, three-year time point to see if there's any benefit overall on histology or any change in histology. So, it's not really been part of our clinical development. It's not part of medical practice within the setting of PBC. However, to provide you with an update since November's call, we have had approximately dozen patients, for which treating physicians elected to have biopsies taken. We don't have baseline biopsies for all of these patients. However, we do know that based on assessments by those physicians and/or pathologists within those centers, they described the histology as being consistent with PBC. So we've not yet seen anything that anyone's identified to us in our study populations with respect to PBC that appears atypical.
Steve Seedhouse -- Raymond James Financial Inc. -- Analyst
Okay, very helpful. Thank you guys for taking the questions.
Sujal Shah -- President and Chief Executive Officer
Sure.
Charles McWherter -- Senior Vice President and Chief Scientific Officer
Thank you. Steve.
Operator
Our next question comes from Jay Olson of Oppenheimer.
Jay Olson -- Oppenheimer & Co. Inc. -- Analyst
Thanks for taking the questions. Is there any biological explanation, even if it were hypothetical, that would support a causal role of seladelpar for interface hepatitis? And is it possible that this is a potentially harmless finding since it didn't seem to be correlated with any liver injuries or adverse events?
Sujal Shah -- President and Chief Executive Officer
Yes. I would say, at this point, again, along the lines, I'm not aware of any expectation that PPAR-delta agonist in seladelpar, in particular, would have a relationship to interface per se. And I would say that, at this point, again, one of the things that we're seeking to understand is really characterize the entire study population in a very independent way, both on treatment as well as comparison to placebo and compared to baseline. So, I think that's really the bottom line is. We didn't expect this. We've never seen it before. Typically, drugs that have been associated with drug-induced autoimmune liver disease or DILI features that include interface hepatitis almost always have some clinical correlate like elevated ALT and AST. They would typically have more advanced necrosis. Drug-induced liver injury is often associated with that, sometimes elevated bilirubin, but also clinical symptoms. You would often expect to see jaundice, discolored urine, maybe flank pain. And if there's an allergic component, you often would see, for example, a drug rash, or eosinophilia. And so, none of those features were found in this study with seladelpar and that's one of the reasons why we've done -- we've initiated such a thorough investigation along a broad range of characteristics, not only the clinical picture, the laboratory picture, but also the histopathology picture and bringing an expertise with experience in all aspects of this and using the graded and staging system for the pathology is key, we think, for sorting this out.
Jay Olson -- Oppenheimer & Co. Inc. -- Analyst
Okay, thank you for that. And maybe if you could talk about if these Phase 2b study results could support a pivotal trial. If the FDA were to agree to remove the clinical hold on seladelpar development, do you think these results would support a pivotal trial or do you think you need to conduct another Phase 2b study in NASH?
Sujal Shah -- President and Chief Executive Officer
That's a good question, Jay. I think it's a bit premature for us to speculate on what else would be required. I will say, again, when we look at the changes in liver enzymes across both ALT, AST as well as gamma GT and alk phos, we see what we would have otherwise expected to see, that the anti-inflammatory benefits of seladelpar, in fact, have translated at 52 weeks to improvements in histology that we think are actually quite meaningful. These results are preliminary, and so the statistics are not included in our press release. But if you just look across other agents that have been studied in NASH to-date, I think we are quite pleased at what we believe to be really the benefits of seladelpar in this population, in fact, appear to have translated. So, I'm unsure about what the next path forward would be. But, again, I think our primary focus is to learn more about what's occurred here and have the potential opportunity to think about paths forward for seladelpar really in any indication. Of course, our most advanced indication was PBC. So, that is a priority. So I'd simply say, to-date, we're pleased with what we've seen with respect to efficacy. I think future steps at this point are unknown.
Jay Olson -- Oppenheimer & Co. Inc. -- Analyst
Okay, great. Thank you very much.
Dan Menold -- Vice President, Finance
Thank you.
Operator
Our next question comes from Ed Arce of H.C. Wainwright & Co.
Ed Arce -- H.C. Wainwright & Co. -- Analyst
Sorry about that. Hi, Chuck and Sujal. Thanks for taking my questions. And thanks for all the extra detail and analysis that you've provided today. It's been very helpful. So, I have two sort of major questions. First is, clearly, you've taken some effort to really detail and delineate all of the clinical findings to-date of seladelpar. You've mentioned how the more than dozen or so biochemical markers all are improving or stable. There's no signs of potential DILI, there's no signs of immunological signals or platelets or coagulation factors, no liver-related AEs.
And so, in light of all of that, first question really is, and I think we've kind of danced around it a bit here on the call is, is it possible that one of the key determinants from this panel that, I guess, would happen in May or June, one of the determinants is that the atypical findings -- the histological findings are either, A, a false or meaningless signal, or B, that the findings were actually real, but somehow not caused by seladelpar. And then, I have a follow-up.
Sujal Shah -- President and Chief Executive Officer
Yeah, I think it's a good question, Ed. Look, I think, yes, you've asked the million dollar question and it's what we believe the investigation is really geared to answer. I think if -- out of the two scenarios you identified, it would most likely be the latter, potentially, if there's a path to move forward that, in fact, it wasn't something caused by seladelpar as opposed to not being there at end of treatment.
And again, I think the framework that we're using to assess both end-of-treatment and baseline biopsies that goes beyond what is typically done in NASH histology review is, in fact, a framework that will give us a much more clear understanding of the patient population even at baseline. So, we're incredibly focused on making sure that the review happens in a fulsome, independent fashion, and executing all the way through a panel review committee to the agency is, in fact, the key priority within the company.
Ed Arce -- H.C. Wainwright & Co. -- Analyst
Okay, great. Thank you. Second part sort of related to this, depending, of course, on the outcome of this panel's work, you have these preliminary topline results from the study. Most of the patients had parallel biopsies. And, obviously, as you noted, the statistics here are still pending. So, we don't have anything in terms of stat sig. But it seems fairly clear to me that at least in the 50 mg dose, it's likely to end up being stat sig, perhaps across all three of these acceptable surrogate endpoints in NASH. And so, given this pretty fairly positive finding here preliminarily, given that you could find that seladelpar may not have been the direct cause of this, how would you see going forward with this data once you've gotten final determination?
I guess what are the next steps with the drug once you've gotten the final determination from the panel and the final efficacy results with statistics?
Sujal Shah -- President and Chief Executive Officer
I think we agree with you, Ed, with respect to the interpretation of the efficacy data in the study. I'll simply say, again, here, we're focused on getting through the independent review and engaging the agency in dialog that'll be pending the results of this independent review. If in fact we come out of the panel review meeting with an ability to argue around listing the clinical hold for seladelpar, not just in PBC, where we are most furthest advanced, but also in NASH and really in other indications, I think we go back to the strategy we ultimately had in hand. We know that within the setting of PBC with the strong set of Phase 2 data, there's a clear unmet need in that population.
With respect to NASH, we've always also felt there's a clear unmet medical need here. And this data, in fact, is encouraging from our perspective. I think with respect to NASH, we've always felt that strategies to develop treatment alternatives would involve studying various agents in combination. I think these data could potentially be supportive of that. But I don't want to put the cart before the horse, so to speak. I think the key element for us is to maintain the focus on the investigation. I don't want to minimize the path ahead of us to get through the investigation and, pending the results, engage the agency in further dialog.
Ed Arce -- H.C. Wainwright & Co. -- Analyst
Okay, great. Clearly, there are some encouraging signs here. And I just want to take a moment to congratulate you on your thorough diligence here and the work that you've done so far regardless of the outcome.
Sujal Shah -- President and Chief Executive Officer
We appreciate it. Thank you, Ed. Thanks for the support.
Operator
Our next question comes from Derek Archila of Stifel.
Ben Porter -- Stifel Nicolaus Corp. -- Analyst
Hey, great. Thanks, guys. This is Ben on for Derek. Thanks for taking my call. Sorry if I missed this, but did you give a reason for why the second biopsy was only done in 152 patients out of the 180 patients? Thanks.
Charles McWherter -- Senior Vice President and Chief Scientific Officer
Yeah, thanks. This is Chuck. It's the usual. We had about 83% to 84% of subjects who had an end-of-treatment biopsy. That's a pretty common range or number, I would say, for a Phase 2b paired biopsy study, a 52-week study. Some of this was related to typical reasons for early terminations or lost [Phonetic] to follow-up. Sometimes, patients don't want to have a second biopsy. And again, we did, in November, terminate the study early. And so, then that was also another impact that patients just decided that they were not interested in going through. So, I think, in my perspective, 83%, 84% is a pretty good number. I think that really doesn't raise any red flags from our perspective.
Ben Porter -- Stifel Nicolaus Corp. -- Analyst
Okay, thanks for the info, guys. Appreciate it.
Sujal Shah -- President and Chief Executive Officer
Thank you.
Operator
Our next question comes from Joel Beatty of Citi.
Joel Beatty -- Citigroup -- Analyst
Hi, thanks for taking the questions. The first one is on the data table in the press release that shows that the statistics are pending final analysis. Could you share what remaining that needs to be done for a final analysis compared to what's shown? Is there any potential for the numbers shown there to change?
Charles McWherter -- Senior Vice President and Chief Scientific Officer
Yeah, thanks for the question, Joel. It's just about an abundance of caution and being very true to the good clinical practice processes. So, the database is not yet locked. So, we're in the process of the final cleaning, quality control, all the typical types of things that need to move us toward a good clinical study report. And so, once all that's understood and recognized, then statistical analysis can be done according to the pre-specified plan. And we didn't want to have to modify that later.
The results are preliminary. So, it's always possible there could be some adjustment, but I wouldn't think that it would be any -- if anything changed, it wouldn't be anything that you would consider significant. The overall interpretation really shouldn't change at all.
Joel Beatty -- Citigroup -- Analyst
Great, thanks. And one other question on PBC. Could you remind us how close that trial was to completion and the amount of data that you collected per patient? I guess where I'm going is, if you get to a point where FDA agrees to lift their clinical hold, what could that data support? Could it support approval? Could it support doing another trial? Where's the trial data at?
Charles McWherter -- Senior Vice President and Chief Scientific Officer
Yeah, great question. And we agree with the sentiment that you're are -- what you're alluding to there. So, the study was completely enrolled. We had full enrollment across 25 countries, more than 150 sites. And in fact that we had significant numbers of subjects through treatment -- through more than six months of treatment and many even through nine months, so we believe that while it's unlikely that trial by itself would be a registration trial, it would be a very significant dataset that could support and be used as part of the consideration for a regulatory decision.
In particular, I'll just remind you that the primary endpoint in that study is a composite looking at cholestatic markers, alkaline phosphatase below 1.67 with at least a 15% reduction in alkaline phosphatase from baseline and a bilirubin in the normal range usually at 12 months, but by six months, there's very little difference between historically what you see in studies between six and 12 months.
Again, another key secondary endpoint was normalization of alkaline phosphatase. Looking at that, at six months, I think would be very informative. And then, importantly, improvement in pruritus, and that was a six-month endpoint. And so, we think we would have a very full placebo-controlled dataset that would really speak to that.
So, just to round out the answer to your question, accordingly, in terms of our clinical wrap-up, we're taking measures to make sure that we collect the data. The data is clean. We close it out. We can get a clinical study report that could be used in the event that we were to go back into PBC with a registration study. And that would be, I think, enormously valuable. A lot of clinical experience there, coupled with our very large open label Phase 2 study, which was also a 12-month study, and which we've extended. We have a lot of patients past -- more than 50 patients past two years of treatment, even some patients with three years of treatment with good results so far in terms of efficacy, tolerability, and the appearance at least of safety.
Joel Beatty -- Citigroup -- Analyst
Great. Thank you.
Charles McWherter -- Senior Vice President and Chief Scientific Officer
Thank you.
Operator
Our next question comes from Mayank Mamtani of B. Riley FBR.
Suowei Wu -- B. Riley FBR, Inc. -- Analyst
Hi. This is Wu on for Mayank. Thanks for taking my question. I've got several quick ones. The first will be on the NASH study. Could you let us know if -- what seladelpar dosage level was [Indecipherable] and will you ever do a Pro-C3 analysis?
Sujal Shah -- President and Chief Executive Officer
I'm sorry. Can you mention the first part of your question again? Can you repeat that?
Suowei Wu -- B. Riley FBR, Inc. -- Analyst
Just what dosage levels were in the study.
Sujal Shah -- President and Chief Executive Officer
So, we studied three different doses of seladelpar in the NASH study, 10, 20 and 50 milligrams. If your question is more related to patients with unexpected findings, again, at this point in time, we think it's important not to disclose those specific details as we have several independent pathologists reviewing, again, both baseline and end-of-treatment biopsies. And so, not to influence their independent review, we'll share that subsequent to the completion of the investigation.
Suowei Wu -- B. Riley FBR, Inc. -- Analyst
Thank you. And also, how about the Pro-C3 analysis? Are you going to do any analysis on that?
Charles McWherter -- Senior Vice President and Chief Scientific Officer
I think the study had a very extensive and rich set of assessments, including non-invasive imaging, MRE in corrected-T1. We have some FibroScan data. We do have some other biomarker data, including fibrosis markers. Those will be shared at some point. I think the entirety of the results of the study, like all our studies, our plan would be to bring them for external review, like a medical conference, and eventually to publish the results. But we're not yet ready to make that disclosure until we get everything wrapped up.
Suowei Wu -- B. Riley FBR, Inc. -- Analyst
Great, thanks. And then, could you let us know if the Phase 2 NASH study had allowed the patients to remain on the baseline treatments, such as GLP and lipid-lowering treatment, etc. or if there was a wash-out period excluding any background treatment?
Charles McWherter -- Senior Vice President and Chief Scientific Officer
Yes. So, they weren't on GLP-1. So, GLP-1s were not allowed per the protocol. But, obviously, these subjects have many different kinds of comorbidities, including hypercholesterolemia, diabetes, all those kinds of things. And they were allowed as appropriate therapies for their underlying conditions. And they would, though, be limited in terms [Phonetic] of what types of adjustments they could be making during the study.
Suowei Wu -- B. Riley FBR, Inc. -- Analyst
Okay. And my last question will be a follow-up on the PBC study. Could you maybe give us more color on the status of the PBC Phase 3 dataset? Is there any timeline for that would be available for this May or June investigator meeting?
Sujal Shah -- President and Chief Executive Officer
It's a good question. I think -- so, we've terminated the study as we previously announced last December. The database lock and cleaning is yet to be completed. And again, as Chuck mentioned, we want to maintain those timelines and the integrity of that data. We don't believe that that data in particular is needed for the panel review. I think it would be certainly helpful data for us to share should we be successful at some point in finding a path forward for seladelpar in PBC. It would be, I think, in our intention, useful to share regardless with respect to just the overall update to the medical community, but not something in the near time.
Suowei Wu -- B. Riley FBR, Inc. -- Analyst
Okay, great. Thank you.
Sujal Shah -- President and Chief Executive Officer
Thank you.
Operator
This concludes the question-and-answer session. I would like to turn the conference back over to Mr. Shah for closing remarks.
Sujal Shah -- President and Chief Executive Officer
Thank you once again, everyone, for joining us on the call today. As we've noted, we're working diligently and expeditiously across each of our parallel work streams. We're incredibly mindful of all of our stakeholders in these efforts, including patients, regulators and shareholders. And we look forward to providing further updates as the work progresses. Thank you.
Operator
[Operator Closing Remarks]
Duration: minutes
Call participants:
Dan Menold -- Vice President, Finance
Sujal Shah -- President and Chief Executive Officer
Charles McWherter -- Senior Vice President and Chief Scientific Officer
Yasmeen Rahimi -- ROTH Capital Partners -- Analyst
Eliana Merle -- Cantor Fitzgerald & Co. -- Analyst
Steve Seedhouse -- Raymond James Financial Inc. -- Analyst
Jay Olson -- Oppenheimer & Co. Inc. -- Analyst
Ed Arce -- H.C. Wainwright & Co. -- Analyst
Ben Porter -- Stifel Nicolaus Corp. -- Analyst
Joel Beatty -- Citigroup -- Analyst
Suowei Wu -- B. Riley FBR, Inc. -- Analyst
