Hi, everyone. I'm Ellie Merle, one of the biotech analysts here at UBS. Thank you for joining us at the Biopharma Conference in Miami. Very happy to have CymaBay Therapeutics here with us today, and joining us from CymaBay is Harish Shantharam, Chief Financial Officer. Thanks so much for joining us. Maybe to kick it off, high level, could you tell us how the preparation process is for the regulatory submissions in the U.S. and Europe? First of all, thank you, Ellie, for having me here. Happy to represent CymaBay, I should say. These are exciting times for patients, you know, with PBC, so and excited with what we, what we've been able to accomplish with seladelpar and what, what's ahead for us in terms of key milestones. But I'll, I'll hit on kind of where we are as, you know, before getting into the regulatory filing and questions you have asked about, you were asking about. So clearly from where we released our positive top-line data, very exciting. We were able to hit all primary and secondary endpoints, and we see the potential for seladelpar to be the only drug which, you know, reduces both the biochemical markers for the disease, but also the symptomatic, you know, symptom reduction, especially on pruritus. So very, very excited. I mean, very consistent data set that we were seeing between phase two and where we landed with the response. So clearly, next step is, you know, getting us ready to have a quality filing, and that's where, you know, the organization is singularly focused. You know, just in FDA, but also, you know, at MHRA and EMA. You know, we haven't provided any formal guidelines, but guidance in terms of timing. But as you can imagine, given this is the NDA and our focus, we're trying to have a quality, you know, submission as quickly as possible. You know, I would say from an expectation setting, I mean, particularly 4-6 months from a top line is a reasonable estimate. So, which is kind of, which gets you to the early part of 2024, but we're trying our best to, you know, beat that for sure, so. Mm-hmm. Absolutely. Maybe thinking about the commercial opportunity, but also the differentiation versus others in development, what do you think is unique about PPAR-δ, even the most selective, and how this is differentiated from others in development, such as elafibranor, or then, you know, also OCA and the potential development with bezafibrate? Yeah. So PPAR-δ is a very, it's a, seladelpar is a selective, potent PPAR-δ agonist, and, sela delpar as it's, and it's expressed in various cell types and multiple cell types, in the liver and, and, and, and something that actually plays a role in, you know, you know, regulation of critical pathways in PBC pathology. The biology of seladelpar mechanism, I would say, has been very consistent with what we've seen in clinical data around, you know, anti-inflammatory, of course, anticholestatic, anti-inflammatory, and anticollagenic benefit. You know, so if you look at these are patients who have high elevated bile acids and, high alkaline phosphatase levels. And the data that we've seen so far, right? I mean, and again, I'm talking about the RESPONSE, the pivotal data, but even going into RESPONSE, we had over, you know, robust data set with our prior phase II ENHANCE study, phase II ENHANCE study, as well as our robust phase II study, which had over 100+ patients. There are RESPONSE data set where we saw about 62%, you know, meet our primary endpoint, which is the composite endpoint, and one out of four patients actually normalized. And then having a statistically significant difference in pruritus benefit were all very consistent with what we've seen. Coming to a little bit on the differentiation, right? What we're working for. We're targeting a market where, you know, we know UDCA, which is the first-line generic. Everyone, you know, we know about 60% don't normalize, right? They don't hit them at the alkaline phosphatase level, that is at normal levels, you know, which is target marker for, you know, disease progression. And, so the only current second-line agent, you know, FXR agonist Ocaliva, you know, we know for, you know, one out of two patients don't hit the composite endpoint to start with, and they have low single-digit percentage of patients who normalize based on their POISE study. So versus the one in four that we've seen normalized for us. And above all, then coming to pruritus benefit, we know Ocaliva actually, you know, potentially increases or has the potential increased pruritus or itch, which is a very debilitating condition for patients suffering from PBC, unfortunately. And what we've seen, not just one study, but two studies, where we've seen, you know, statistically significant reduction, right? So, you know, so clearly, I think this plays a very critical role from an activation perspective. I think this is where the mechanism, what I've been saying, is not just the anticholestatic, but the fact that, you know, you know, seladelpar is expressed, you know, in the macrophages and, you know, and in the circulating, both the resident circulating macrophages and Kupffer cells, I think plays a role, has in terms of the anti-inflammatory effect, and it's, you know, it's also translating it for antipruritic effect. The, you know, the question on elafibranor, we know very little to be able to really have a fair comparison. Again, when I do these comparisons, again, the caveat being these are across studies, so, you know, all the caveat withstanding. But when it comes to, I mean, maybe specifically on elafibranor, we know the, we know very less. Obviously, the top-line data, what they have shared was very, you know, limited versus, you know, what we put out. Of course, we'll know more, as you know, they share the results at their summary at AASLD next week. But what we know, of course, the composite endpoint was likely lower than what we had. They were not able to hit the statistical significant difference in pruritus, which is going to be an important one. And of course, the normalization is one thing that I'll be looking at. I know we know what their phase II data has been more on the lower end, like between 10% and 12-13%. So again, that's something that we ought to wait and see where elafibranor is. But what excites us from a differentiation perspective, and I think it's maybe I'll use leverage kind of our breakthrough therapy designation that we got from FDA. We're like super thrilled and gratified because it would clearly emphasize and underscore the potential for seladelpar. And previously what was our breakthrough therapy designation was just early PBC, but now it includes PBC including pruritus and also including patients who you know without cirrhosis and with compensated cirrhosis. Again reflecting kind of the data that we've been able to generate even the full response. So clearly I see this a differentiator. I mean what is how is this going to translate commercially to your question? I mean, I would like to think it actually increases the probability of an indication statement, including that includes pruritus. But of course, we've got to wait and see in terms of the part of the review where FDA lands. But I do think this is definitely a, you know, we see it as a real positive outcome, you know, for seladelpar. Mm-hmm. Yeah, I'm surprised more people aren't talking about the updated breakthrough designation. If you were to get this in the indication statement, what would this mean in terms of the number of eligible patients that could be treated with seladelpar, and how to think about the commercial impacts of that? Sure. Let me, so, in terms of the broader commercial opportunity, we estimate about 70,000-75,000 patients are treated in the U.S. And as I said, actually, six out of 10 actually don't get normalized instances by starting UDCA and being on treatment. At the time of our, you know, I mean, potential approval based on response, if we're successful, there's an addressable of about 21,000 patients, who are, you know, have elevated about 1.67x upper limit of normal, which is the criteria for a response study. So that would be an address, needed addressable patient population. And while 9,000 of those patients have tried Ocaliva, based on our estimates, two-thirds have actually discontinued based on indicated to various factors. Pruritus could be one, I mean, efficacy could be another factor. But these are, so that clearly is a low-hanging fruit of patients who discontinue. But there's also a significant number, another 12,000, so to speak, who haven't, you know, who are technically second-line eligible patients who we know are progressing the disease, will benefit from a, you know, treatment like seladelpar, what we think is, you know, clear opportunity for us. So those are kind of the immediate, again. So when you think about, and this includes the fact that now, if you're successful in including having cirrhosis in that, based on our data set, I think it's just clearly from a physician perspective, I see this the broadest spectrum of patients who will be a candidate for, who could benefit from seladelpar, right? We're not making a choice. You are not making a choice for, you know, would my symptom worsen with this, where I'm not having any choice, or is it, can I use it for a cirrhotic, you know, like Child-Pugh A patient? So clearly, it gives us an opportunity for us to go after the broadest patient pool. But that's just the beginning. Where we think it goes after beyond is, I mean, I'll start with normalization. One of the data, the feedback that we are getting now and what excites you know physicians and our thought leaders from response is the first thing that they go to is actually normalization. To say, "Hey, jeez, this gives me an opportunity to normalize one out of four patients," right? So clearly, that's the goal, where 1.67x is kind of our is a regulatory endpoint, and that may limit our payer considerations early on. But the goal is to normalize, and that's where our, I would say, our ideal study kicks in, where we're going after patients who are, you know, currently above ULN, but less than 1.67x and are not part of any of the current second-line criteria. But we think as we generate data from an ideal study, our second-line opportunity pool, that will only expand, and to almost double actually the size. So that gives us. So I think I would say it. We have a profile and a data set, a data set that where you don't have to make compromises or choices because, you know, we're clearly, there's an opportunity to differentiate on every aspect of efficacy, you know, symptom benefit, and not least of which, I mean, I should probably add here, is also safety. You know, we have over 500 active exposures of seladelpar for patients in seladelpar B, and it's continuing as we speak now in our long-term study. And so that would be. I see it as a huge differentiation as well versus elafibranor. I mean, if you think about it, they had about 45 patients in their PBC phase II study. So clearly, we see there's an opportunity, the robustness of the data set. Of course, we'll have an opportunity to share the full profile, you know, next week, and so I don't wanna, you know, go too much deeper there. But what we had shared earlier, the top line was it's consistent with what we've seen in the past, and that is actually a fairly weighted statement because for us, it's based on much more robust data set. So we think safety could be a differentiator as well. Mm-hmm. Absolutely. Well, I'll, I won't ask you about the data that you'll be presenting next week, but I will ask you, heading into AASLD, what are you looking to see from a competitive perspective, from the elafibranor data that would, say, make you more confident in your competitive positioning? What could you see that might make you less confident in your competitive positioning? And any particular kind of benchmarks in thinking about the rate of ALP normalization, the specifics on the magnitude of effect size on pruritus, that you would say this amount of difference is meaningful to physicians, but this amount of difference might not be. I mean, how are you thinking about that going into this update from elafibranor? Well, I can tell you what we're focused on, with respect to, you know, our data set and what we will – the type of data we hope to share more, you know, next week. Of course, one is, you know, in the top line, we were able to show the absolute endpoints that we had shared. So I think it is important to share. For full appreciation of the profile, I think we would like to – we will be sharing this, as we've done in the past, like after our top line, and we go, when we shared in the medical conference. We would share the onset and, you know, durability or duration of response is something that we'd like to share for. We will be sharing in our, for primary and secondary endpoint, so clearly that's going to be important. Are we seeing a sustained, you know, pruritus benefit? Are we seeing ALP normalization? What is the, you know, the trend looks like of the 12-month period? So those are, I think is going to be an important one, to share. Then number two, I would say, is things that we have not, shared, but we, you know, but it, you know, is, is important. I mean, in other inflammation, liver injury markers like ALP, which is... I mean, in the past, we've seen about 20% drop, you know, in our phase II data sets, and now we'll have an opportunity to share what that looks like in our RESPONSE. That's going to be one. I mean, lipid parameters is some another one that we've, you know, we'd like to share and something that physicians always call out and say, "Well, yes, the patients may not have a huge cardiovascular risk," but if you have a drug, basically go by our phase II data and prior ENHANCE, and if it improves your, it uses LDL, it's actually a benefit for our patients and, you know, unlike probably what we've seen at OCA. And of course, we'll have to wait and see, you know, what alirocumab data looks like across, along these parameters. So that's - and then the safety is going to be a critical one, right? I think I already mentioned that earlier. So for me, those are the parameters. Then compare, of course, I mean, we feel good with what, you know, the data we have and the profile that we, you know, we think seladelpar presents. Of course, we'll have to wait and see, you know, from a competitive dynamics in the profile, how it plays out to elafibranor, but I would say, you know, we'll, we feel good going in. Mm-hmm. Absolutely. It'll be interesting to see the details of the data. Heading into potentially your first product launch and filing next year, how are you thinking about the commercial preparation, the size and scale? And then from the cost perspective, how much do you expect this will cost? Sure. I'll. So we're—I mean, our commercial, pre-commercialization efforts, pre-commercial planning, it already is in full swing, is what I would say now, that we've just even actually accelerated now that we are other side of data, so to speak. Our MSLs, our medical team is on board. You know, we've most of the majority of about 12 MSLs we're targeting are already there. In fact, it's, I mean, I see AASLD as somewhat of a coming out party for CymaBay, because I think it's an opportunity for us to showcase our for our medical teams, in fact, showcase, you know, the data set and have a chance to meet the top leaders. So, you know, with and their investors and encourage them to, you know, swing by our booths next week. So I mean, so a lot of... So we're already, so the medical team is already on board. They're already on the field with some, you know, data dissemination in our, you know, basic PBC education. And, that's happening as we speak. The commercialization we have on the commercial front, I would say, all the commercial leadership team is in place, talking about market access, you know, commercial operations, analytics function, the marketing. So that's all in place. Obviously, these are all important critical pillars, and we've, in fact, beyond market access, I would say probably there's about one step lower. We're already, you know, building out the field team that their team is already there so that we can start to present ourselves and educate the payers on PBC and the advancements there, that's happening. Again, this is also a place where medical can help us from an education perspective. And then the sales, you know, field probably will come in, you know, it's usually more closer to a PDUFA date once we have a sense of where that timeline looks like. So it's not uncommon to expect that two months before. You know, so that's kind of where we are. So we've, I mean, we're excited where we are. We're, you know, things are moving in full swing, brisk pace, I would say, for U.S. commercialization efforts. I mean, with respect to the cost, you all, I'll refer to the cash runway that I shared, the guidance that I shared yesterday, at the earnings. I mean, our cash runway should give us what we need to support our operating expenses through into the first half of 2026. Again, always say it's, you know, you have one chance to launch. You gotta make it right, so but we feel we have the strong balance sheet that has enabled us to have a strong launch for sure in the U.S. So that's clearly what, you know, kind of where we are. Mm-hmm. More work to do, more work, there, but I think the team is excited. Mm-hmm. Absolutely. You have exciting phase III data, and, you know, certainly commercial preparations are underway. But in terms of thinking about, you know, strategic options, particularly commercialization ex-U.S., how are you thinking about the puts and takes of the advantages of commercializing yourself or engaging a partner, and the framework that you're applying in thinking about what would drive the most value? Good question, Ellie. I mean, so from an ex-U.S. perspective, maybe I'll call out first that we have a partner in Japan that we signed early in the year. One of the reasons we went to that region, one of that geography first, because we know there's gonna be some bridging studies that will be required from Japanese regulatory requirements. We wanna get a head start there, so we found an amazing partner with Kaken, and I would say we had a very, you know, strong financial terms. So in a way that, in that sense, it set the benchmark for what we may end up doing in Europe. With Europe, we're actually, we feel we're not in a rush to... You know, we wanna have the strategic optionality to actually have those rights with us. It doesn't mean we've been engaging with our, you know, with various, you know, potential partners and players who could, you know, potentially get seladelpar quick as faster. So that's always there. We're evaluating that, you know, the partnership potential. At the same time, we feel that the balance sheet we have, that we don't need to immediately make the call now, and just have the strategic optionality, you know, be it, you know, be it for inbound or if you're doing it, or, you know, if you end up doing, adding, you know, some, looking at some value growth opportunities where we think it makes sense for us to own the rights. So we're also evaluating that, and it may also involve us, you know, having a more staged launch perspective. We know, U.K. and Germany, for example, drive 50%-60% of the potential there, so we have an opportunity to have a more staged launch if that makes sense in the long term. So that's kind of where we are. So we're keeping our options open, and we don't feel like we're, you know, you know, against the wall to make this call right away, but, I mean, something that we will be, you know, making a decision soon. Mm-hmm. Absolutely. We talked earlier about some of the advantages of your data in pruritus. Thinking from a competitive landscape, we're expecting to get some of the initial data from the IBAT inhibitors in pruritus. How are you thinking about that in the context of your data, and how you think about market segmentation? Particularly since if you get an indication statement, theoretically, that could maybe open front line for the patients with pruritus, and how you're thinking about the potential competition from IBAT inhibitors? You know, good question, Ellie. I mean, when I think about IBAT inhibitors, that's purely for cholestatic pruritus, right? If you really think about it, they don't necessarily, you know, improve, you know, the markers for the PBC disease by itself. They don't reduce alkaline phosphatase, for example. So really, it's not a. I mean, we're going after a PBC patient, where it's important to get the ALP down. And the question, so it's going to be more where the patients are, right, in terms of spectrum, in terms of, you know, disease progression is probably where if the patient is completely almost early first line, if maybe IBAT inhibitor may play a role, but if you're like, you have slightly elevated, you know, ALP and then where it's important to reduce both the ALP marker and you wanna have greatest benefit, obviously, clearly that's, you know, it's where seladelpar would play. So we don't. So I see it as a bit of a different category first as itself, because clearly that's not, I mean, they wouldn't be, they won't be treating PBC and it's purely an, you know, you know, you know, you know, dealing with, I guess, the cholestatic itch. Mm-hmm. Absolutely. One of the most common questions I get from investors is how to think about the size of the market opportunity. We talked about the large number of patients, but we've also seen a commercial launch with Ocaliva that's treating a minority of them. Of course, we've seen your data and improvements on itch. How should we think about, you know, the dynamics in terms of the number of prescribers. Mm-hmm. And, you know, a little bit of the decentralized nature of the treatment of PBC and your confidence that, you know - 'cause theoretically, if you treat even half, I mean, half these patients, that'd be a massive, massive market. But how are you thinking about the accessibility of these patients, these practices, and the degree to which you can get them to prescribe seladelpar? No, again, I mean, the activating the patients is kind of where our, the commercial team's whole focus is on, right? Because we know there's this opportunity out there, and I, I'd want to call out, I mean, clearly, you know, I don't think it's the right to frame this market through the lens of probably what Intercept had been able to achieve, just because there's some of the limitations as we know with the profile. But also, again, if you just look at the persistency and discontinuation, I mean, you may be looking at a different market size if it was, you know, had a persistency similar to the first line agent, for example. So clearly, I think in terms of the different value proposition that seladelpar presents, I mean, clearly we see an opportunity to go after a much more broader pool. Where are these patients, right? I I mean, majority of these patients are treated by, you know, hepatologists and GI docs, and in fact, the hepatologists are probably, I mean, it's less than 200, in fact, but they treat probably 8x-9x or more than 5x compared to the rest. So it's a very concentrated problem. You'd expect, you know, some of the early adoption from there. It is important to go after the broader GI, you know, treated doctors and, you know, GI, gastroenterologists who treat the majority of the PBC patients. So clearly, the team is, what we're doing right now is actually, you know, for our sales force site and structure, optimizing our target plan and, you know, how do you-- what would it take to activate the patients? Who do you go first and who do you go next in terms of, in a more, you know, phased approach? But clearly, that's kind of... You know, we're going through that exercise now to be able to, activate those patients, I think, you know, is what we need to do. Mm-hmm. I see we're almost at time, but one quick one. Do you expect to have an adcom? You know what? I wish I would know one way or the other. I mean, you know, if we feel we have a very robust, like, you know, good profile and data set. We've had a fantastic, great engagement with the regulatory, you know, regulatory bodies over years. So it's, you know, and have a robust data set. So I well, I don't know one way or the other if that's going to happen. I don't think anyone knows at this point, but we're prepared either way. So but I think, I mean, the engagement, the recent engagement, even on breakthrough was, I mean, a kind of a thing reflects, I think, you know, what I see as a strong partnership and with the regulatory bodies. So, we'll be prepared either way. Great. Well, with that, thank you so much for joining us, and thanks, everyone, for joining us in the room.