Hi, good afternoon. Welcome to the JP Morgan Healthcare Conference. I know it's late on a Wednesday, and I see some tired faces, but I promise this is the best one we have today. My name's Raji Gunasekera. I'm with the Healthcare Investment Banking Team at JPM, and today I'm pleased to introduce the CymaBay Therapeutics team and their CEO, Sujal Shah. Thank you, Raji. We appreciate this opportunity to talk to you all about the exciting work happening at CymaBay. I'm gonna walk you through really five series of discussion points. I'll talk a bit about CymaBay, who we are, how we got here, and effectively, where we're going. I'll talk a bit about the therapeutic area we're focused in: autoimmune, rare liver disease, primary biliary cholangitis, or PBC. Talk about the disease and the unmet needs that patients still have today. Want to spend some time talking about seladelpar. All of us at CymaBay consider ourselves fortunate to be working on such a unique target and potential product candidate for PBC patients. Talk a little bit about the mechanism of action, as well as some of the latest data, phase III, that we presented at the end of last year. I want to spend a little bit of time talking about how seladelpar meets the potential unmet needs for patients, and how we think ultimately seladelpar will really drive a resetting of treatment goals for patients, and ultimately resulting in better treatment options and outcomes for patients as well. I'll finally talk a bit about commercial preparations. That's effectively where we are in 2024, looking to get seladelpar finally into the hands of patients. Before I begin, I'd like to remind folks that I may be making forward-looking statements during today's presentation, and I encourage you to review the risk factors inherent in our operations as set forth in our SEC filings. While 2023 was, without question, a seminal year in the 30-plus year history of CymaBay, successful phase III data, NDA filing, significant value creation for all stakeholders, our shareholders, but importantly, thinking forward about patients. The real exclamation mark comes in 2024. It's ultimately the year in which we finally advance the journey to bringing seladelpar, if successful, with regulatory approval into the hands of patients. What's even more exciting for us is that this is really just the beginning. We've completed phase III, but we have multiple ongoing clinical studies advancing to continue to give us greater insight into how seladelpar will, in our minds, transform the treatment landscape for patients today. We believe we are ultimately on the precipice of transforming this treatment paradigm, most importantly, transforming the very lives of people living with PBC. 2025 and beyond, we'll continue to commit ourselves to advancing this care for patients. So who are we? Let's start there. The company has had a rich history of both drug discovery and development, metabolic disease, autoimmune disease, significant expertise in inflammation and fibrosis. All of this, from our minds, is culminating on trying to fulfill improving lives of patients without suffering. The transition in this year is one in which CymaBay hopes to move from a development company to a commercial company. Our leadership team, our executive leadership team, has all the experience across functions to deliver on these goals in 2024 and beyond. The entirety of the executive team, in fact, works alongside a depth of an organization that I couldn't be more proud of. In 2023, we really built out our clinical operations, our clinical development teams, on top of the strong, rich history and research throughout the needs for us to bring seladelpar to patients, CMC, quality, regulatory, and now a commercial organization and a medical affairs team ready for the next stage of this transition. So I talked a bit about the transformative year we had in 2023. Much of that is highlighted on the left-hand side of this slide. The beginnings of seladelpar's development in PBC, in fact, started in 2015. Wide range of phase II dose-ranging study, really focused on ensuring we had a great appreciation for the potential benefits of seladelpar in this setting. In 2023, we continued ASSURE, our long-term study, in which we have now north of 300 patients taking seladelpar once daily in an ongoing basis. This is a study from which we will continue to mine meaningful sets of data, looking for information that we have an opportunity to share at upcoming medical meetings throughout the year, even as we push towards potential approval and launch. Early last year, we licensed rights to seladelpar to Kaken, a partner of ours now in Japan, leading the development to bring seladelpar to this important region and to these patients. Throughout the course of 2023, ultimately, we shared the phase III data that I'll give you some appreciation for today as well, but much of the build-out, as I mentioned, about our medical teams augmenting those in internal commercial. Another study we initiated last year was called IDEAL. We'll talk briefly about IDEAL, but it's largely a recognition we have that as treatment goals change and evolve, there's an opportunity to almost double the addressable patient population for second line treatment. This is our commitment to advancing care for patients, not just in today's view, but those that are left untreated and left to progress. All of this culminating in execution and expansion as we move forward from 2024 and 2025, regulatory filings, approvals, and preparing ourselves once again for committing to generating new data sets while we put this drug in the hands of patients, should we be successful. Let's pause for a few minutes and talk a little bit about PBC, a rare chronic, progressive, fibrosing, inflammatory fibrosing liver disease. The disease affects roughly 1 in 1,000 women over the age of 40. Ultimately, as an autoimmune disease, this is a progressive liver disease causing damage to the intrahepatic bile duct, a buildup of toxic bile acids, and again, a progression from inflammation to fibrosis, ultimately cirrhosis, and the need for liver transplant. Prevalence in the United States is believed to be about 130,000. When you drill down to those diagnosed, roughly 85,000 and about 70,000-75,000 today are on first-line treatment. I'll dive in a bit later around the segments of those populations being treated and the opportunities for seladelpar. PBC, in fact, is associated with elevated markers of cholestasis, namely alkaline phosphatase, but also gamma GT and bilirubin. These markers provide surrogate endpoints for conditional approval pathways as they have a high likelihood of potentially predicting outcome benefit in patients with PBC. The other challenge for patients with PBC is symptom burden, fatigue, as well as pruritus. The latter, in particular, we'll spend some time talking about today. Unmet needs that significantly impact the quality of life for patients. Treatment goals remain to slow the risk of disease progression, but at the same time, reduce symptom burden. There's only one first-line treatment approved for patients with PBC, ursodeoxycholic acid, and only one second-line. Despite these two treatments, there are significant unmet needs. Roughly 60% of patients never experience a normalization of alkaline phosphatase on first-line treatment. That results in progression. These patients remain at an increased risk of progression, potentially towards the need for liver transplant or death, certainly other liver-related unwarranted effects. Given this progression, up to 40% of patients, in fact, progress to cirrhosis over the course of their disease. In this population today, there are limited second-line treatment alternatives. Finally, back to pruritus. It's believed that up to 70% of patients may experience itch or pruritus in the course of their disease, up to 40% experiencing moderate to severe itch, significantly, as I mentioned, reducing quality of life. Today, there are no effective antipruritic treatment options for patients. We'll drill down a bit more on pruritus once again. First-line treatment with ursodeoxycholic acid has never been shown to reduce itch. The only approved second-line treatment, obeticholic acid, can cause or exacerbate itch. That's the current landscape. We talk about itch, as I mentioned, prevalence as high as 70%. A recent study and survey suggested that the quality-of-life impact of pruritus in PBC patients is similar to that of Parkinson's disease, something many of us are more relatable with. The treatment guidelines for pruritus include a host of offline treatments with minimal benefits and significant side effects. Ultimately, AASLD guidelines will require or suggest cholestyramine, a bile acid sequestrant, rifampicin, other treatments like naltrexone and sertraline, as you know, that have significant side effects. So again, nothing significant to address this plaguing symptom for patients today. So let's turn our attention to seladelpar. Seladelpar is unique, unique target. It's the first in a class of targets called delpars, targeting the PPAR delta nuclear receptor. PPAR delta is unique, particularly for inflammatory liver disease, as it's expressed in each of the major cell types in the liver and regulates all of the key pathways important in PBC biology. First, I'm going to start on the lower right-hand side. One of the most important impacts of PPAR delta agonism in PBC is an inhibition of bile acid synthesis.... As I mentioned, bile acids accumulate given impaired bile flow in PBC patients. Seladelpar is known to inhibit bile acid synthesis as well as cholesterol synthesis, impacting a reduction in alkaline phosphatase and slowing potentially disease progression. We know mechanistically that seladelpar has an impact not only on lowering bile acids, but also on lowering serum IL-31, an inflammatory cytokine that has been associated with pruritus, now in PBC as well as in other settings, including atopic dermatitis. We've shown that seladelpar reduces serum IL-31 and that those reductions in our clinical studies correlate to the reductions in pruritus patients report when taking seladelpar. So groundbreaking, potentially, as I mentioned, with the ability to actually improve quality of life for patients with PBC. We also know that seladelpar, given its mechanism, increases lipid metabolism. There's an added benefit for patients of reducing total and LDL cholesterol, as well as increasing fatty acid oxidation, ultimately resulting in decreases in triglycerides, so an added cardioprotective effect. And finally, a reduction in inflammation. One of the unique characteristics of PPAR delta is its expression in circulating macrophages, as well as the resident macrophage cell type in the liver, Kupffer cells, where it's known to cause a polarization from the M1 pro-inflammatory to the M2 anti-inflammatory phenotype. As a result, we see a host of inflammatory cytokines that go down, as well as systemic markers of inflammation, including hs-CRP. Uniquely suited for a chronic inflammatory liver disease. I'll briefly touch upon the key pivotal data announced last year. RESPONSE was our phase III global, well, placebo-controlled, double-blind, 52-week pivotal study, randomizing 193 patients at a 2-to-1 randomization between seladelpar 10 mg and placebo. The primary outcome measure, composite responder rate based on alkaline phosphatase reductions, as well as normal bilirubin, is a primary composite endpoint that has been used and validated to support conditional Subpart H approval for second-line treatment in PBC by regulators around the world. Two key secondary endpoints include normalization of alkaline phosphatase. As I mentioned earlier, the lower you bring alkaline phosphatase, not just below 1.67 x the upper limit of normal, but further into the normal range, gives you the ability to potentially further improve and slow the risk of progression for patients. And finally, a key secondary endpoint looking at the change in the numerical rating score, pruritus. This is a zero to 10 scale in which 10 represents the worst imaginable itch. Zero is no itch. We measured this NRS for patients that entered the study with moderate to severe itch, as defined by an NRS score of 4 or greater at baseline. The secondary measure was to compare that six-month endpoint versus baseline. I'll flash just some of the key takeaways from this study, which we presented once again in a late breaker presentation at AASLD in Boston last November, and for which we have also submitted for publication and hope to see that out soon as well. Three key takeaways. Effects on alkaline phosphatase. We achieved a 62% response on the primary composite response rate, highly statistically significant relative to the placebo arm. 25% of the patients on the seladelpar 10-mg group experienced alkaline phosphatase normalization versus zero in the placebo arm. Key impacts from an anticholestatic benefit. We also saw antipruritic effects. These patients that I mentioned came into the study with moderate to severe itch, in fact, had a baseline itch of 6.2. We saw a 3.2 drop in the seladelpar arm. Again, highly statistically significant versus what was experienced in the placebo arm. We saw this benefit on itch, not just on the NRS endpoint. In fact, we see this benefit when we look at other tools and measures. The 5-D itch score that's utilized in PBC, as well as the PBC-40 questionnaire, that also includes itch domains. With those measures that also correlate to quality of life, we saw statistically significant improvements even in sleep disturbance. And finally, the study with seladelpar in RESPONSE demonstrated 0 treatment-related serious adverse events. Overall, as you can see in the presentation given at AASLD and ultimately in our forthcoming publication, a safety and tolerability profile that was comparable in the treatment arm versus placebo. As it pertains to adverse events related to pruritus, in fact, there were a greater number of adverse events in pruritus in the placebo arm, correlating once again with the effects we're seeing where seladelpar provides benefit. So this profile, ultimately from our perspective, is in line with where we believe new treatment goals will advance. The real objective for patients shouldn't just be to bring them to lower cut points of upper limit of normal with alkaline phosphatase and shouldn't be simply to manage itch. We should be treating patients to normal. We ultimately believe treatment guidelines will evolve to be explicit around normalization of alkaline phosphatase as a goal. We should be treating symptoms, not just managing them for patients... seladelpar has the potential to be the first treatment alternative to give patients an opportunity to actually improve quality of life and experience an improved life while also slowing disease progression. And all of this, if done with a safe and well-tolerated treatment alternative, we believe offers the opportunity to also treat patients early, the best way to truly slow progression. We fundamentally believe that based on the profile to date, seladelpar has the opportunity to potentially serve as a foundational second-line treatment in PBC. Our commitment, however, didn't end with the RESPONSE phase III study. As I mentioned, we have three ongoing studies, and I'll start at the bottom of this slide. AFFIRM is our phase IV clinical outcome study, a very unique clinical study design, three-year fixed duration in a population with significant unmet need. The study is enrolling compensated cirrhotics with Child-Pugh A or B. This is effectively our phase III-B/IV commitment, not just to regulators, but also to patients. The study was initiated last year and will be ongoing and continues to enroll. The ASSURE study, as I mentioned, now with north of 300 patients, bringing back patients from our prior phase II and prior ENHANCE study, as well as over 90% of patients from RESPONSE that elected to continue on seladelpar once daily in this open label study. Again, a very rich study in which we will have the opportunity to understand efficacy and safety one year, two years, and beyond, and continue to mine data sets that we'll look to share in upcoming medical meetings throughout the calendar year. And then finally, IDEAL. This is a study in a patient population that's not explicitly highlighted in treatment guidelines today. These patients have an alkaline phosphatase above the upper limit of normal, but below 1.67 x the upper limit of normal. They're not deemed to be as high a risk as the patients that we've been typically studying in phase III trials in this setting. Nevertheless, they are at a higher risk of progression than patients that experience full normalization on first-line treatment. We think this is an innovative study. It's the first of its kind in this population. Once again, these are patients that have never been offered clinical studies before. We think there's an opportunity for seladelpar to demonstrate meaningful normalization, normalization in alkaline phosphatase for this population, really potentially driving a significant uptake in the addressable use. Let's talk a bit about that addressable patient population. This is a market segmentation done specifically for the U.S. population. 130,000 prevalence, as I mentioned, approximately 85,000 of which are actually diagnosed. Here, we've taken Symphony script data and Symphony claims data to look specifically at the 70,000-75,000 patients that are being treated with first-line UDCA today. 23,000 of these patients, the left-hand bar, are patients whose alkaline phosphatase remains above 1.67 x the upper limit of normal. That's roughly 200 units/L. Normal is between 100 and 115 units /L. These are the patients, once again, that are largely identified as having the highest risk of progression. Of these patients, currently, there are as few as 3,300, roughly, on second-line treatment today, largely because of some of the significant challenges around tolerability, safety, and even efficacy. The opportunity for seladelpar is to potentially improve a significant number of significant outcomes for a significant number of these patients. The IDEAL study transitions us to expand the addressable population to the bar on the right. Almost another 20,000 patients, roughly, that fit in between that 1-1.67 x the upper limit of normal bar. Once again, patients that could benefit from biochemical normalization. As the IDEAL study enrolls, we'll provide some further updates to that study throughout the course of this year. Our strategy is ultimately to execute a study showing normalization, also measuring itch, and to utilize that data, if positive, as a supplemental NDA for future label expansion that will, in time, along with guideline changes, allow for the potential use of second-line treatment in almost 42,000 of these 70,000-75,000 patients. So significant growth in the addressable population ahead. I'll shift gears here briefly in the next two slides to talk a bit about commercial priorities. I'll go rather quickly so I can leave some time for Q&A. I talked already about resetting expectations. We followed closely patients' journeys, and we know that the solutions ahead need to address both immediate and long-term treatment goals, ultimately further supporting the evolution of physician and patient expectations. Our focus remains on driving rapid adoption at launch, focusing on high-volume treaters and maximizing patient access through rapid coverage, reimbursement, as well as patient support services. Ultimately, the pursuit of excellence, excellence for all of us, is fundamental inside of CymaBay. To give you some appreciation on how broad these activities have been, while we filed the NDA ahead of schedule at the end of last year, our launch readiness efforts have been well underway for some time. Supporting the product potential, we are ensuring we have all the right brand strategy, CMC, and manufacturing, as well as distribution strategies, strategies in place, supported by the right platforms... all fueled by an incredible team, an assembled medical team that includes a number of individuals with experience in PBC, significantly strong relationships with the medical community, hepatologists, community GIs, continuing to build commercial leadership across all internal commercial functions. Market access planning is now underway, and the sales field team hiring will be up ahead. I appreciate the opportunity once again to give you a greater appreciation for where we've been and ultimately where we're going this year. In the end, this journey for years has always been focused on the final goal, and we're excited this year to ultimately not just move treatment goals for patients, but to bring a new treatment alternative to patients with PBC. Thank you. Thank you, Sujal. Next up for Q&A will be joined by Chuck McWherter, who is the CSO and President of R&D. Firstly, congrats on a huge year and the big milestone. I guess the obvious question is, you know, pruritus, why haven't we heard so much about this symptom in the past? And why do you think it's gonna drive so much of market dynamics going forward? Well, maybe I'll start, and I'll let Chuck add some color. You know, it's always challenging when patients are burdened with a clinical symptom where there's no treatment alternative. First-line treatment, as I mentioned with UDCA, doesn't reduce pruritus, and second-line treatment, of course, today actually can cause or exacerbate itch. And so many patients actually report that their physicians even don't ask them about itch, in fact. You know, I think in the end, physicians, of course, want a slow progression of disease and focus on biochemical markers. The focus is on liver enzymes and laboratory measures, and with limited alternatives, I think many just don't have the opportunity to really ask, given there's limited options for them. I think that's fundamentally something that we're gonna look to change. You know, with seladelpar and the effects we see, as I mentioned, consistent across a number of different tools and parameters. Chuck can even talk a little bit more about some of the biology of what we've learned and the importance of us elevating the ability for us to now actually treat symptoms for patients. Yeah. Well, I think it's, of course, very common in medicine, a challenge that a patient has a symptom. It's not anything you can measure. It's only what the patient tells you. And it's challenging for both physicians and the patients to really wrestle with that. You know, am I being believed? Am I, am I getting a response? What's, I think, transformed in just a very short period of time, is advances in an adjacent area of medicine, in dermatological itch. Over the last few years, it's been understood that IL-31 is a so-called itch cytokine, has been demonstrated to have a role in pruritogenic signaling. And in fact, there's therapeutics that are approved in Japan as well as in development in the Western world, so IL-31 receptor blockers. The real breakthrough for us was an understanding that in cholestatic itch, you have a buildup of bile acids because of a loss of biliary function. Well, the bile acids activate its receptor, the FXR receptor, and that has been shown to cause production of IL-31, and it's a known cause of itch. So we simply examined in our clinical studies, well, what happens in PBC patients? We're able to show in a publication that appeared just a couple of weeks ago in Hepatology, that PBC patients have 30-fold higher levels of IL-31 than matched healthy volunteers. So that was kind of the smoking gun. And then we went on to show that bile acid levels correlate with IL-31, so it kind of matched up with triggering the bile acid receptors, causing this itch-signaling molecule. And then we were further able to show that the baseline patients' report of the level of itch matched with those two. That's pretty exciting. And then finally, kind of the cap to the story was that we were able to show dose-dependent reductions in all three bile acids, IL-31 and itch. They traveled together. And so I think it's built a really strong story, and I think it's kind of circling back to you're a patient. You have a complaint. You hope to be believed. It's common enough you are believed, one would think, but there's nothing you can measure. We now have something that at least we can measure. It really gives, I think, you know, reality for patients, and it's really opened up the lens in cholestatic pruritus, not only for seladelpar and PBC, but any disease in which you retain bile acids in the liver. Looking ahead, what are your expectations for timing and approval, and your thoughts on whether the FDA will hold an advisory panel or AdCom? Yeah, sure. So with the filing in the U.S. going in, mid-December last year, we have Breakthrough Therapy Designation, under which we have requested Priority Review. With the 60-day clock, we hope to hear back from regulators around acceptance of the submission sometime in February. If it's accepted on the normal timelines, without any questions, then we would expect, with Priority Review, perhaps an August PDUFA date. But those are yet to be determined. We'll learn more from regulators as we hear back from them sometime in February. ... Got it. And, when do you anticipate completing enrollment for the IDEAL study? And also, what is the timeline around label expansion for that? Yeah, so, you know, IDEAL, as we mentioned, was a study that we're conducting in patients with Alk Phos between 1 and 1.67. It's an important label expansion strategy and an opportunity, again, to serve patients that are not served today with treatment alternatives. It's a study that we continue to evaluate as we look at what we need to do to advance in order to measure both biochemical marker of disease as well as symptom burden. We haven't yet given specific guidance on the timelines to complete IDEAL. As we get further into enrollment, more sites initiated, more site screening, we'll provide some updates likely sometime this year around those timelines. And so it's a little bit premature for us to talk much more about the timelines for the regulatory strategy as well. I think in my presentation, I mentioned that ultimate goal for us is to actually submit that as a part of a supplemental NDA, again, assuming that we get approval sometime this year. What are your expectations around seladelpar uptake, given that you might have a new competitor potentially launching around the same time? Yeah, I think, you know, ultimately, we anchor on the profile of this drug. We're confident that seladelpar has demonstrated a unique ability to normalize Alk Phos in a significant number of patients. We think that's differentiated also from other drugs in development. It really is the only drug to have demonstrated a statistically significant benefit on itch, now in two separate global phase three studies and across various parameters, as I've mentioned. And we think the safety profile, in fact, is also advantaged for seladelpar. So, you know, I think we're confident there's an opportunity for significant patient care with two new potential alternatives entering the market, both of which we believe will continue to drive an awareness for normalization as a goal, both of which we believe will continue to drive awareness around pruritus. And I think in the end, it's a benefit. Certainly, it's a benefit for all patients, particularly in an area where there could be a doubling of those numbers of patients actually treated, when you have two new treatment alternatives entering the market at the same time. Just thinking about, you know, ex-U.S. strategy, do you plan to launch in Europe on your own or maybe seek partnership? Yeah, I'm glad you asked. As I mentioned, we filed in the US at the end of last year. We've indicated that our goal now is to file as quickly as possible in both the EU and in the U.K., guiding towards those submissions in the first half of this year. The work is ongoing now to accelerate those filings. For now, we're continuing to evaluate the opportunity either for us to license rights in Europe. We're gonna take some time to evaluate all strategic alternatives in front of the company today. And we're also gonna, in parallel, understand what a launch would look like if we did it ourselves in Europe. So I think for now, the good news is we have some time. We have the ability to file on our own and to evaluate all the variety of strategic alternatives in the company. We won't commit yet, but each of these tracks is ongoing now. To the extent you're able to share, you know, do you plan to take seladelpar into any other indications, maybe PSC? Maybe check that out. Yeah. So I think that's a great question, and I think it's important to point out that both diseases are cholestatic diseases. They're autoimmune. It's a high unmet need. There's nothing available to treat PSC. It's really a tragic diagnosis to receive. I think it makes sense that seladelpar could potentially be leveraged to treat PSC, but for now, we see the opportunity as squarely on treating PBC. I mean, getting the approval in place and then expanding the market, there's a lot of value there to be harvested before we turn our attention to looking at PSC. Got it. That's helpful. Could you just walk us through sort of what are your key upcoming events, updates, or milestones for the company in 2024 and maybe even early 2025? Yeah, sure. So I think the first is an update as we hope to see the agency accept the submission, as I mentioned, February, providing an update around when the potential PDUFA date would be, again, assuming that filing is accepted. Those are the most near-term, I think, updates. As I mentioned earlier as well, we submitted the full phase three dataset for publication. Hope to have that out imminently as well. I think that's important, an important opportunity for our medical team, to take that dataset, and inform physicians around the outcome of our study, and of course, allow people to compare across other treatment alternatives as well as those in still in development. I think through the rest of the year, as I mentioned, we'll always look to medical meetings. We've had a history, and Chuck and the team have had a history of submitting abstracts, sharing datasets, ultimately publishing them, but we'll look forward this year to congresses like DDW, a significant congress for GI, as well as liver, as well as EASL and AASLD through the course of this year. And then ultimately, again, we're preparing ourselves for commercial launch, expecting a successful outcome and hoping for a successful outcome. Obviously, getting to, as aggressive of a launch as we can is ultimately what we're focused on. Great. And, again, looking ahead, could you sort of talk about your, your cash balance and how much runway you have at the moment? Yeah. We, we reported north of $430 million at the end of September last year. The guidance around cash runway remains that we have cash into the first half of 2026. That guidance does not include any potential contribution from revenue, so there's always the potential on timelines that we project to have almost a year and a half, potentially, of launch behind us. I think fundamentally, the cash on the balance sheet allows us to commit to a launch in the United States. Great. Thank you very much. We'll now open up the audience for any questions. Questions? No. All right, if not, we can end a little early. Thanks again to the CymaBay team. Thank you all for attending and all the best. Thank you. Appreciate it. Thank you, Raji.