CymaBay Therapeutics, Inc.
Q2 2019 Earnings Call Transcript

Published: 8 Aug 2019

[Operator:]

Greetings, and welcome to the CymaBay's Therapeutics second Quarter 2019 Conference Call. [Operator Instructions]. As a reminder, this conference is being recorded.It is now my pleasure to introduce your host, Dan Menold, Vice President of Finance for CymaBay Therapeutics. Please go ahead, sir.

[Daniel Menold:]

Thank you, operator, and good afternoon, everyone. I hope that you've had a chance to view the press release we issued announcing second quarter 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; 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 and timelines and potential development outcomes 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 forecasts due to the 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 statement 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 the recording or rebroadcast is expressly prohibited without the written consent of CymaBay.At this time, I'd like to turn the call over to Sujal.

[Sujal Shah:]

Good afternoon, everyone, and thank you for joining us. In the first half of this year, we have made significant progress driving seladelpar forward and ENHANCE a global Phase III registration study in patients with primary biliary cholangitis, or PBC. ENHANCE is currently active in 23 countries across 5 continents and at more than 145 study sites. We are targeting an NDA submission for seladelpar and PBC in mid-2021. And the study is currently on track to complete enrollment by the end of this year with top line results expected soon after completing the 52-week treatment period.The advancement of seladelpar towards the market has injected significant energy and planning for the next stage of seladelpar and the company. For that reason, I couldn't be more pleased to have announced earlier this week that Janet Dorling is joining us as Chief Commercial Officer. Beyond executing on our clinical plan, our most important goal is to develop a cogent commercial strategy and to build out a commercial team for implementation. Bringing over 15 years of experience in commercial sales and marketing to CymaBay, Janet is ideally suited to this high-priority effort. As Chief Commercial Officer at Achaogen, she built a commercial organization and launched the company's first approved product. Importantly, for roles at Genentech and Roche, included VP Global Product Strategy for the breast-cancer franchise and VP U.S. sales and marketing life cycle leader. I expect there will be many opportunities going forward for you to meet Janet and to appreciate as we have her outstanding leadership skills and the depth of her acumen, and of course, to periodically learn more about our plans for seladelpar as she works with us to advance our goal for bringing it to PBC patients.The focus of my opening remarks on PBC is quite intentional, given the significant results reported to date in our open-label Phase II study that has enrolled 119 patients. Seladelpar has consistently demonstrated a pattern of anti-cholestatic, anti-inflammatory and have paddled protected effect through 52 weeks of treatment. Our enthusiasm for seladelpar is not only derived from the robust responder rate but the composite endpoint that combine Acklin phosphatase and total bilirubin, but also because it has done so without exhibiting the signs for causing or worsening pruritus as seen with the only approved second-line treatment.Furthermore, the potential for seladelpar to improve pruritus is a key secondary outcome in ENHANCE and will be monitored using an electronic diary. This profile, which was observed in Phase II, suggested to us that seladelpar may have the potential to be positioned as the preferred second-line treatment for patients with PBC.Our confidence in the seladelpar safety and tolerability profile has further been bolstered by our experience in Phase II where 104 out of 106 eligible patients have elected to rollover into a long-term safety extension. The safety experience continues to build as we now have a significant number of patients in the extensions study that have been treated for over two years. As the core of the Phase II study is completing, we expect to present the data from the study that will provide a robust 52-week set of results in early 2020, about 1 year in advance of top line ENHANCE Phase III results. And subsequently, our goal will be to publish this data.I would like to remind those in the call that seladelpar's potential extends beyond PDC. I will shortly described two other active Phase II development program with seladelpar. One, for nonalcoholic steatohepatitis, or NASH. Aand one for Primary sclerosing cholangitis, or PSC. We believe the actions of seladelpar through PPAR Delta agonism is uniquely suited to reduce inflammation both directly through its effects on cooper cells in the liver and circulating macrophages, and indirectly by decreasing several key drivers of inflammation and liver injury, including bioacid in the setting of PBC and PSC and lipotoxic lipids, precholesterol and bile acids in the setting of NASH.Let me now turn to recapping recent events in our NASH program. In early June, we announced interim 12-week top line data from our ongoing Phase IIb dose ranging study of seladelpar. This study enrolled 181 patients with biopsy-confirmed NASH, advanced fibrosis with over 80% having stage 2 or 3 fibrosis and high baseline liver enzymes, reflecting liver inflammation as part of their ongoing disease.As a reminder, we reported 12-week top line results showing a striking pattern of reductions in liver enzymes known to be associated with liver damage and pathology, but with minimal changes in total linever fat content as explored with noninvasive imaging. The study remains blinded to the 52-week end-of-study biopsy to evaluate NASH pathology and fibrosis.Seladelpar treatment resulted in a robust comment also ordered and clinically meaningful reductions in key markers of inflammation and liver injury, including Alamein our ALT. Seladelpar is does represent an improvement in liver enzyme markets and the potential associated with sister pathology has generated considerable interest in understanding the effects seen at 12 weeks will translate into histological improvement at 52 weeks.Patients receiving the 10, 20 and 50 milligrams doses of seladelpar achieve mean ALT reductions of 15, 20 and 32 units per liter, respectively, versus a decrease of 9 units per liter in placebo-treated patients. It was encouraging for us to see a consistent pattern of improvements with seladelpar treatment in other liver enzymes withreduction seen in AST, GGT and alkaline phosphatase including an over 40% reduction in elevated GGT at 50 milligrams. To put the results into context, a recently published an analysis of histological responses in the FLINT study for Obeticholic acid found that it decreases in ALT of 17 units per liter or greater were correlated to an improvement in histological response. Data published from other NASH studies have also supported the association of ALT reduction with improvements in NASH histology.Other key results at 12 weeks included decreases in the inflammatory marker, HSCRP, as well as decreases in LDL-cholesterol and triglycerides supporting a favorable cardiovascular risk profile.Seladelpar appeared to be safe and well-tolerated at doses up to 50 milligrams through 12 weeks. The majority of treatment emergent adverse events were mild to moderate in severity and deemed unrelated to study drug. There were 2 serious adverse events that had occurred after amortization through week 12, neither of which was deem to be related to study drug.While we're surprised and disappointed to not see a meaningful reduction in total liver fat at 12 weeks, we believe that reductions in markers of liver damage our encouraging and supported by what is known about seladelpar mechanism of action. We look forward to establishing this logical evidence of seladelpar's benefiting NASH, a second population in addition to PBC with a serious inflammatory liver disease.As a final portion of my clinical update, let me share our excitement as we turn to development of seladelpar in primary sclerosing cholangitis or PSC. Commander cholestatic fiber inflammatory disease. mechanistic underpinning of seladelpar's activity in cholestasis, inflammation and fibrosis it is to initiate clinical development in this division disease for which there is high unmet need and no approved therapies. We recently announced that we had concluded successful regulatory interactions with the FDA and are initiating a Phase II study of seladelpar in patients with PSC. PSC is a rare area chronic cholestatic liver disease that is characterized by diffused inflammation and fibrosis of the bile duct, the disease predominantly effects the medium- to large-sized bile ducts inside and outside the liver, and as manifested by ongoing ductal destructions leading to cholestasis, advanced fibrosis and cirrhosis. Patients are also at high risk of developing cholangiocarcinoma. PSD is an orphan disease affecting approximately 40,000 patients in the U.S. and share some underlying pathology with PBC. Although it is generally a more heterogeneous disease.Activities for the study are well underway, and we expect to begin screening patients this quarter. The Phase II study will be randomized placebo-controlled dose ranging that will enroll approximately 100 patients at 60 sites globally. Seladelpar at doses of 5, 10 and 25 milligrams once daily will be studied versus placebo in 1 to 1 to 1 to 1 [ph] randomization. The primary efficacy outcome will be the relative change in alkaline phosphatase with baseline at 24 weeks.Key secondary endpoints will include FibroScan, imaging evaluations, including RI with contrast and MRCP and other exploratory measures, including serum biomarkers of inflammation and fibrosis.My goal today has been to summarize the status and potential of seladelpar in inflammatory liver disease, well down the path for global registration for PBC. We have begun building out our commercial team to develop and implement plans for launch and market success. We've continued to execute in NASH with signals of improvement in liver damage await histological readout in the second quarter of 2020. And now, we're embarking on a proof-of-concept study in PSC, yet another orphan cholestatic disease that we believe fits well with seladelpar's mechanism and offers the potential to extend our franchise into yet another underserved patient population.Turning briefly to our financial, our cash, cash equivalents and marketable securities, we're $241.2 million at June 30. 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 3 and 6 months period ending June 30, I will refer you to the press release and to our 10-Q filed with the SEC today.I'd now like to open up the call for questions. Operator?

[Operator:]

[Operator Instructions]. Our first question today is coming from Eliana Merle with Cantor Fitzgerald.

[Eliana Merle:]

Can you just give us a little bit more color on the PSC study? I know you mentioned that you're looking at a lot of secondary and exploratory metrics, but just what are your thoughts on, I guess which of these metrics will be predictive of long-term outcomes? And we know that out class reductions is not as tightly linked to long-term outcomes and key PSC such as PBC. Just curious of your thoughts there? And then maybe your thoughts post speaking with the regulators as well? And what they're thinking in terms of these [indiscernible] thinks?

[Sujal Shah:]

Yes. Thank you for the question, Ellie. I'll start off and perhaps ask Pol to add anything that I may have missed. PSC like PBC is, in fact, a cholestatic disease. So alkaline phosphatase is actually a very important indicator overall of the level of cholestasis that patient's experience, and we expect it to be at least part of a key measure and understanding the overall benefit for patient's long-term. You're absolutely correct that in the setting of PSC, there is, in fact, a greater degree often of inflammation as well as fibrosis you typically see, particularly, in early stage PBC. And so what we're looking to do with the host of secondary markets, including imaging as well as wet biomarkers of both inflammation and fibrosis is to get a better understanding overall of the impact of seladelpar on liver health. Now this is a 24-month -- 24-week assessment in this space to study. So these are all largely providing us some indication of the potential impact overall longer-term on both inflammation as well as fibrosis. And fundamentally, the regulatory agency hasn't yet firmly described an endpoint outside of histology and biopsy in PSC to date, while recognizing similar to PBC where biopsy is uncommon, there's a tremendous amount we think we'll learn from these secondary endpoint on markers that may in fact correlate overall to liver health.

[Operator:]

The next question is coming from Yasmeen Rahimi from Roth Capital Partners.

[Yasmeen Rahimi:]

So a couple of questions for you. So let's start off with PBC. So can you tell me a little bit more about what type of PROs have you built into ENHANCE that ensure sort of high orphan pricing for seladelpar? And then the second question is on NASH. So I know we've had some time to go back probably to the top line, is there any nuances that you learned that you would like to share with that, specifically around reasons why placebo response ran higher-than-expected? And then I have a quick follow-up.

[Pol Boudes:]

Yes, me, this is Pol. So we'll take the first part of the question for PRO for ENHANCE. So as you know, the main PRO we are using is actually the reporting of priritus, which is done by the patients. And we are using an electronic system and we're now using the NRS scale and that is going to confirm our hypothesis, our internal hypothesis that we not only do not see association between seladelpar and pruritus but potentially we -- a beneficial effect to treat pruritus. For the other PROs, we are using as you know the PRO, which has been specifically developed for PBC, which is called the PBC 40 scale, which is an interesting scale because it's -- what is really specific in way for PBC is that there's a lot of [indiscernible] and in this scale, it's really focusing on fatigue, which is really one of the main symptoms for pruritus with PBC patients. We are using other scales, but I would for pruritus, we have something called that's 5G pruritus sales, which is 5G mentioned pf pruritus. But the main PRO pruritus is going to be on IRS. And that's going to be a key signal outcome for this study.

[Charles McWherter:]

Yes. This is Chuck. We're continuing to try to broaden our view on understanding the placebo effect, and in fact, the liver fat content. We're hampered to a degree because we're still blinded in the study. The study will remain blinded all the way to 52 weeks. So pretty much limited to the top line group averages. We will be conducting number of additional biomarkers assessments that will focus and allow us to examine things like markers of fatty acid oxidation, lipolysis, some other characteristics of inflammation, effects on bile acid synthesis, which is also a key factor associated we believe with NASH pathology, but at this point, until we were able to get down to patient level data, look at the population see if there is an association, for example, with weight loss or other baseline psychological factors, it's little challenging to put a very specific interpretation on it.

[Yasmeen Rahimi:]

And you guys have done an amazing job in getting into late [indiscernible] AASLD and EASL. Can you give us a quick glimpse into what we should be seeing at the upcoming Liver Meeting in Boston?

[Sujal Shah:]

Yes, Yasmeen, I think as you've seen from us over the past few years as we've advanced seladelpar and PBC. And as we've now taken our first steps into NASH, we'll continue to have a presence at key medical meetings, including AASLD this fall as we've had at prior meetings. We continue to learn quite a bit about seladelpar, mechanism, the chemical structure and how we think we're seeing benefits in various patient populations. So without too much specificity until we're able to obviously share any details or until these are determined ultimately, I'll shy away from being overly specific. But fundamentally, we continue to see seladelpar advancing, particularly, in the setting of PBC. Not just through Phase III, but ultimately if we're successful to an NDA filing. And all of the efforts that we continue to focus on here internally as well as externally in the medical community are largely focused around making sure people understand what we've learned thus far with our experience with seladelpar. How we believe it will impact patients longer-term if we continue to be successful. So you'll see our activities continue to broaden, not just from our own clinical experience but of course, we've been very active at holding our own advisory boards, investigator meetings, activities that are really crucial and fundamental to the way we think about continue to move seladelpar forward ultimately getting it in the hands of patients.

[Operator:]

And the next question is coming from Steven Seedhouse from Raymond James.

[Steven Seedhouse:]

Given you had a Chief Commercial Officer and are beginning to build out a commercial team for PBC, can you just talk about the near term priorities and deliverables for that team just given the NDA submission would still be almost 2 years away based on current timelines?

[Sujal Shah:]

Thanks for the question, Steve. This is an intentional effort here to build really just a core team to think through the overall commercial strategy. So we'll be very deliberate in a small team here on the commercial front that Janet will clearly lead. And just understanding the patient needs, understanding the overall market, understanding how the impact has been for really the only second-line treatment approved recently that based on Phase III data provides adequate benefit in only about half the population and also has a tolerability issues as we know in terms of causing or worsening pruritus in some patients. So part of what we'll be doing and part of the effort that that Janet will lead is just better understanding the market and the nuances overall for patients so that we're best positioned as we approach NDA and as we ultimately approach launch in terms of the way we think about the strategy for seladelpar, not just with the first filing but thinking through opportunities to continue expanding patient population and activities that we can ultimately invest in longer-term to get seladelpar in the hands of as many PBC patients that we believe will benefit. Now outside of even just commercial, we've got a very specific and focused effort on medical affairs.In fact, we've made several key hires of individuals in medical affairs as well as former MS sells that have been -- that are now field directors. These are individuals that now the PBC space quite well. They know the liver space and hepatology field quite well also. And really have been active in these areas for quite some time. So we feel great about some of the additional team members that have joined recently that built up our efforts in the metaforas [ph] area well.

[Steven Seedhouse:]

Okay. And speaking -- just going back to that second line agent in PBC, it continues to slowly churn higher in terms of its uptick. I'm curious if you've seen over the course of the Phase III ENHANCE, and evolution in the type of patients you are enrolling? Are you enrolling more patients that are OCA-experienced as the study has proceeded? Or has the commercial use of those OCA has been impediment to enrollment at all?

[Sujal Shah:]

Sure. So we do see patients that have been on OCA and many cases are not able to tolerate or make the decision, they're not able to tolerate that treatment. I wouldn't say we've seen any impediment. I think you're absolutely correct. Part of what we're seeing with, I think, the continued strong launch of Ocaliva is an underpinning of the tremendous need for additional treatment alternatives for patient. And so despite its tolerability issues, I think what I -- what we saw earlier today was in fact a very strong quarter and a continued very strong launch. And from our perspective, everything that we see as we continue to enroll patients in ENHANCE, our population of patients that continue to have a need, both for what we believe seladelpar is the potential to deliver, which has improved efficacy as well as better tolerability.And so fortunately for us, on the heels of that has been very strong Phase II data that's been presented in the medical community over the past 2, 3 years with seladelpar, the strength of that data set is largely fueling our ability to continue to enroll ENHANCE in our overall timelines that we pre-specified as we initiated this Phase III study. So we continue to see strong support. I mentioned in some of the opening remarks that in our Phase II study of the 106 patients eligible to roll into the long-term extension, we see 104 of those 106 elect to effectively stand seladelpar treatment longer-term. And today, in fact, we are seeing many patients that are now out to two years. So overall, what we see fit of our experience I think it's largely fueling our ability to continue to enroll ENHANCE, even in an environment where the uptick and scripts and sales overall for Ocaliva continue to increase.

[Operator:]

Our next question today is coming from Ed Arce with H.C. Wainwright & Company.

[Antonio Arce:]

Just a couple of questions from me, some have really been asked, but a couple here. First, with regard to POC, obviously there is some similarity with PSC but of course PSC is strongly associated with IBD mainly ulcerative colitis. And I would venture a guess that probably has something to do with the higher inflammation in fibrosis that you see little bit earlier in the disease. Just wondering how you think about controlling all that sort of externality, if at all? Or how that impacts the way you thought about the design of the trial?

[Charles McWherter:]

Yes. Thanks, Ed. This is Chuck, I'll take a run at it. So I think I'll come back to your design question in a second. I think the -- just to kind of speak to the co-morbidity of IBD and PSC about 70% of patients with PSC do have IBD as well. I think the disease is often complex and incompletely understood. But I think it does make sense that there's a component of cholangitis is that assuming current bacterial pressure on the liver from the underlying IBD. So the kind of the inflammation, the recurring pattern of infective pattern, which is a common feature of PSC is one likely is incompletely described connection between the two diseases, and obviously, the risk the underlying common autoimmune characteristics of the diseases as well. We were fortunate because CymaBay was able to recruit Steve Rossi as our VP of Early Clinical Development. He came to us from MGM where he'd run a PSC study before.And the value to us of that expertise is really just been able to develop a study design that had been informed by experience and the complexity of PSC study not just population with uncommon IBD, as you've mentioned, but also study endpoints. In this particular case, the experience about being able to balance the desire to have a simple clean population versus the practicality of being able to enroll a population really led us to position. The story will enroll patients who have IBD, we need to be able to do that. Will be back on therapy for IBD, and I think that's probably makes a lot of sense because at the end of the day, that kind of the background therapy that exist in the population at any rate. so you want to be able to have a measurable effect in the face of those converts. So I don't think that really represents less there is position, the investigators involved in the study very experienced in managing these patients, the tools that you use to evaluate their baseline IBD is very clear, there is clear specification and the protocol in terms of them having had an assessment ahead of time like colonoscopy and then a baseline assessment about episodes, if you will. But they need to be stably controlled. So we don't think and based upon Steve's experience, I think it's well informed position that there's going to be any specific challenges relative to IBD industry.

[Antonio Arce:]

Okay. Great. On the other question, I guess, around PSC, and I know that we -- this was touched upon on the last call. But in the absence of a sort of definitive registrational end point for PSC as of yet. And I know there's some further work going on with this, but are there any updates in terms on how to think about what particular endpoints, if perhaps maybe a composite endpoint or one or the other would most likely for a pivotal study in PSC?

[Pol Boudes:]

Add, this is Pol. I think this discussion is ongoing what is the appropriate endpoint for Phase III program. I think some people are favoring to have us as part of the composite biopsy outcome. And when you look at the biopsy, I think the component that is really a part of this evaluation of the tissue is fibrosis, actually. And it's a little bit easier in PSC to evaluate that compared to PBC, for example. So I don't have a definitive answer. The good thing I would mention is the discussion between academia, the FDA, also the European authorities and sponsors so there is the liver program, which is a very good vehicle for this kind of discussion. So we'll see when it will be established. I think it makes sense to have some kind of composite outcome because also it's a rare disease. So when you go in Phase III, probably it makes things a little bit easier also in terms of sample size calculations. Well I think, for us, at the moment what is really important is the proof of concept for PSC. We are kind of optimistic because we already have the proof-of-concept of the anti-cholestatic effect in PBC. So we'll see -- it's going to be an interesting evolution.

[Sujal Shah:]

I guess the only other comment that I would add is that there seems to be a evolution to think about PSC. You could kind of say in some sense an analogy to what's happening in NASH. So to think about noncirrhotic and cirrhotic PSC. And so those subpopulations may lend themselves to different kinds of endpoints. If you're noncirrhotic, you have the potential to progress to cirrhosis. So blocking that or having some measure whether it'd be an invasive measure like a biopsy and maybe an evolution towards accepting noninvasive measures, which are clinically suspected services something like that. But it would be biochemical markers or noninvasive test, whether it be very clear market or perhaps a measure like liver stiffness, something along those lines. So I think that we're understanding that those two subpopulations really represent some interesting but somewhat different approaches in terms of what the endpoints might end up looking like.

[Antonio Arce:]

Great. Well that's obviously helpful. I would think even for rare diseases moving away from a biopsy is a bottleneck is always going to be helpful. Thanks for the comment.

[Operator:]

Our next question is coming from June Lee from SunTrust Robinson Humphrey.

[June Lee:]

It appears that we've had a bit controversy around liver fat reduction or lack thereof and the reason we reported Phase IIb. Both of our liver specialists, [indiscernible] on a recent clinic, they were actually both highly positive on the [indiscernible] of the data. And thought maybe the lack of a run phase might have contributed to the motivation-related reduction in the placebo group. Love to hear your thoughts on that? And if you have any plans incorporated in the learning Phase II to press the placebo expected in the pivotal study? And I have a couple of follow-ups.

[Sujal Shah:]

Yes, June, it's a great observation. I don't think we can dismiss that, that may have been a possibility, particularly, for what was seen with placebo. Again, I think as Chuck mentioned, until we have patient level data, it will be challenging for us to ultimately determine what we've seen relative to the placebo group so far at 12 weeks. As it pertains to our thinking in Phase III, of course, everything that we learn as we get to the completion of the study at 52 weeks and have an opportunity to understand the impact of seladelpar on histology will truly inform how we think about the broken part going forward for seladelpar. And each of the considerations around the study designs, for example.To bring will be the types of things that we certainly think through. I think on your first point, we also see a tremendous amount of enthusiasm as we have conversations with a broad group of torpedoes with respect to what we saw at 12 weeks. Absolutely somewhat surprising and certainly and disappointed not to see a total fat reduction. But what we do see is ultimately indicative of the improvements you would want to see that would otherwise related to an overall improvement in liver health and manifest in an improvement in histology. And so we continue to see a significant amount of enthusiasm for the consistency, their business of the drugs and key liver enzymes, both ELT as well as GGT, which the latter being really a very sensitive marker of oxidative stress. The manicured, the dose order vision that we've seen, these are the things that I think the most encouraging with respect to what we've seen so far at 12 weeks. So we'll continue to remain very focused on seeing the study in completion and ultimately saying early in point that will help define how we think about clinical development going forward.

[June Lee:]

Great. And please correct me if I'm wrong as I'm still getting up to speed on your programs, but I recall you mentioning you quantify inflammation using an noninvasive method called cT1 at baseline and at 12 weeks. Are you able to share anything on that? And what kind of correlation there between cT1 (sic) and histopathology?

[Sujal Shah:]

CT1, yes, this is coming from the multi-pair metric MRI technology from Perspectum call liver multiscan. We've implemented that for each of the patients in the Phase II study. And as Chuck mentioned, that's one of a number of additional biomarkers and perimeters that will be assessing ultimately to try to get a better idea of what we're seeing thus far at 12 weeks. So it is, in fact, as you mentioned a quantitative measure of inflammation through noninvasive imaging. We think it can -- it is still a year exploratory, everything as we look at the overall picture across multiple perimeters, it can only continue to be somewhat informative of what we're seeing thus far and what we ultimately see pathology and other records to some of these noninvasive biomarkers, including cT1.

[June Lee:]

Okay. And lastly, what are your plans for the end of Phase II leading with the SBA prior to the Phase III study? Will you wait for the entire 52-week study to complete before you meet with the FDA? Or will you or have you already started dialogue with them with the data on hand?

[Sujal Shah:]

No. I think ultimately, the plan given histology forms the basis for the regulatory endpoints for Phase III. We'll wait until we get out histology and have the full data set from the Phase IIb study again we expect to have histology data in the second quarter of next year. We'll do that before we go and meet with the agency for the end of Phase II.

[Operator:]

[Operator Instructions]. Our next question is coming from Mayank Mamtani from B. Riley.

[Mayank Mamtani:]

Congrats on the progress. Just back on PSC. If I'm not mistaken, there is a workshop in September. And the reason I only asked that is, is there any guidance document from a regulatory standpoint now that we have learning from a number of other trials. I think in the end you mentioned that Gilead and others have also worked on it. And then on PSC progression, my understanding is that cholestasis is more of a driver in a more advanced forms of the disease. So could you maybe comment -- maybe built on what you really talk about the screening of patients in the study?

[Sujal Shah:]

Yes. Sure, Mayank, I'll answer the first part and I'll ask Pol to comment specifically on the patient population. There've been ongoing efforts by way of a specific forum outside of the liver forum that's centered and focused on PSC, and called the PSC forum. As Pol mentioned, it includes individuals from industry as well as regulatory agency and thought leaders alike. All working towards the dialogue with respect thinking about clinical study designs and endpoints in the setting of PSC. it's been an ongoing effort. The group mused at least once or twice in the year. On the call, the organization will in fact continue. That hasn't yet been a specific guidance that's been released by the group clearly, PSC, but it ultimately the type of think that the group typically does and works through. So we are involved in the dialogue and have been, and will continue to be but it will be something that would expect to see at some point in time as the group continues to understand and develop a thesis here. Mayank, can you repeat the second part of the question with respect to the PSC population and really cholestasis around how we think about enrolling?

[Mayank Mamtani:]

Yes. Sure. Obviously, we understand it's a heterogenous population but just on the cholestasis bit, my understanding is that the more advanced forms have died as the underlying disease drivers. Just from a patient selection standpoint, are you planning on maybe enrolling more advanced forms of PSC versus maybe less advanced? And I don't know how you measure that? Is it biopsy are you thinking? Or other measures like liver enzymes?

[Pol Boudes:]

It's Pol. So in terms of advanced disease, there are different ways you can approach that. I think the first degree to me if you want is to have cirrhosis or announce roses. The study we're going to complete will be in a non-Cirrhotic patients. Because the severity population really -- it creates different kinds of evolution and inclusion, exclusion criteria. So that's one thing. One way relatively new tool, which is called the [indiscernible] scan, which are also offered to look at BML for fibrosis in the liver, and that's also a nice way to evaluate the patient's in terms of potential cirrhosis. Chuck mentioned also that we're going to get patients who have associated IPD, but the patients. We do get in the study are basically would call that while IBD, they are controlled and in general, and based on previous studies, it doesn't seem that it's really a company factors.So nice way to control the speed goal. In terms of cholestasis, we're going to recruit the city-based on the IP levels, so should be in evolution of the AP level. What is a little bit different from what we've done in PBC is that we are requesting patient to not to buy will AP at baseline. So they will be a limit by the AP that we should have during the screening period. And the last points, which is pretty similar than PBC activity is the level of the European. So that's also convenient way to exclude patients who were up too high bilirubin so we will enroll patient twice the upper limit of normal, which is basically what we are doing also in PBC because when you are in a cholestatic disease above this level than the population start to be a little bit different also.

[Sujal Shah:]

The only other thing I would add it and this is very common for contemporary studies as diagnostic and the staging of the patient's with client geography. So you use an imaging that is one of a few available and commonly available used imaging to look at the biliary tree to -- well, for one thing, to reduce possibility that they also have a cholangiocarcinoma but also to look for the characteristics of PSC in terms of segmental dilation and structure and make sure they have stable dominant structure. And also to focus on the appropriate type of disease because there are different characteristics small legacy sources like that, and dramatic versus and extrahepatic. So I think there is -- information, Steve, and also of course we have I think the best available input from KOLs and Ad Board, we're getting focused in on the most modern and contemporary approach for appropriate selection of patients in this noncirrhotic population.

[Mayank Mamtani:]

If I can squeeze a follow-up to that, are these outflows and bilirubin levels -- and I know it's a band, are these higher or lower relative to the baseline screening criteria you have for PVC trials?

[Pol Boudes:]

It's Pol, I can make a general statement not related to specifically to the studies. But if you look at studies in PSC compared to study in PBCs, the PSC patients tend to involve in clinical trial tends to have higher level of alkaline phosphatase and sometimes also they have more viability in the alkaline phosphatase. So cannot really comment on what we're going to get in this patient but I suppose it's going to be more or less the same thing. We would expect the market expect levels that is going to be a bit higher than what we see in PBC.

[Mayank Mamtani:]

Great. And then on previous, and just piggybacking on the earlier conversation and in sending your caliber a strong results earlier today with Janet on board, I mean, are there any work streams requirements and the inner diagnosis on the disease? In other words, are we -- is there any sign to make an inference that maybe the penetration rates are improving and that patient population?

[Sujal Shah:]

Yes, it's a good observation, Mayank. Of course we'll spend little bit of time better understanding the undiagnosed population. Part of this population are let's say at times are symptomatic. But there are many that are symptomatic and not yet fully identified. So I think in the efforts of having additional treatment firmly raises awareness and helps to increase that undiagnosed patient population fundamentally. But we'll spend a fair bit of time. It's a good observation. that's part of why we do fundamentally believe that the opportunity and the need for patients. In PBC is one that will continue to see growing.

[Operator:]

We reached the end of our question-and-answer session. I'd like to turn the floor back over to management for any further or closing comments.

[Sujal Shah:]

Thank you, Kevin. I'd like to close with just a few important points that we touched upon today that I think often get lost when external attention as the company is disproportionally focused on a single data point or single news event. First, we continue to believe there is a significant need for improved treatment alternatives for patients with PBC as we've discuss today. We believe seladelparis best positioned to deliver both improved efficacy and tolerability for these patients, should our Phase III mirror what we've seen thus far in Phase II, where we're studying the same doses of seladelpar over the same treatment duration in the same population across the same and point. Our central focus has been and continues to be on delivering seladelpar to patients with PBC, and with the addition of Janet to a senior team, will begin the work to solidify the commercial strategy and effort that maximizes decided to patients, their caregivers and all supporting the advancement of this program.Second, along with others working in the NASH field, including sport leaders, and we continue to learn more we study about the most effective ways to target and treat this disease. What we've seen thus far and whether seladelpar is a profile of a therapeutic candidate that has a clinically meaningful effect on multiple markers of inflammation and liver injury, improved cardiovascular risk parameters, and as far, it's generally faced and well tolerated. but Phase IIb study was designed from the outside is to include a 52 week biopsy to access the effects of our seladelpar on the only 2 regulatory endpoints, NASH resolution and fibrosis. Getting the market given the striking effects that we've seen across key liver enzymes of the market observed with the seladelpar with over 12 weeks of treatment, we could do look forward to the 52-week histology data in the second quarter of next year. And finally, the consistent anti-cholestatic and anti-inflammatory effects we met with seladelpar multiple medical settings article in PBC, has given us a tremendous amount of excitement about moving forward this quarter in PSC. We once again no approved treatment alternatives exist for patients today. We will. As we highlighted in the opening remarks the end we continue to execute on the activities that we've discussed here today and look forward to providing further updates in the future. Thanks again for joining.

[Operator:]

Thank you. That does conclude today's teleconference. we disconnect your lines at this time, and have a wonderful day. We thank you for your participation today.