Good, good afternoon, everybody. Where's the camera? Yes, we're gonna be doing this for Tony. Good afternoon, everyone. Thank you so much for joining our Piper Sandler Healthcare Conference. My water. Really excited to have the team from Sagimet Biosciences here. Lots to cover in the next 25 minutes. Maybe a great place to start is AASLD, right? We just recently came from the conference. Could you maybe kinda capture your high takeaways from the liver meeting, and then go into what was the new data that Sagimet presented at the conference? Sure. AASLD, you know well. The pinnacle of... Yeah Liver disease. Lots to learn. There were four pieces of data, which are actually not drug specific that I thought were very good. Okay. One modeling study is showing that NASH will go up by about 25% over the next couple of decades. Yeah. NASH-related cirrhosis by 50% over the next couple of decades. So staggering. Yeah. Staggering amount. The second has to do with AI pathology which is definitely gaining ground. Yeah. I think, we've seen several presentations by the major players. Yeah. It's becoming more and more important for us to better understand disease response. The third one was, Rohit Loomba presented an analysis from MAESTRO-NASH, which... MIT, yeah. ... in a pre-specified manner, confirmed that PDFF is one of the best. NITs, among other... Yeah. ...pieces, but PDFF in particular. And finally, data from the NAFLD NIT Consortium that Stephen Harrison presented. Over 6,000 patients from several drug trials. Actually, we are... Yeah. ... we are part of the companies that give data, and they found a number of ways through NITs to better screen patients to reduce screen failure. Yeah. Among all the things that they presented, FAST Score. Was the best one. And we know that screen failure rates and NASH are very high. This is very useful. No, that's very helpful. And could you maybe also talk about, you had, two posters that were presented there. What was the data presented in the poster, and how does this data increase our conviction column? Sure. We'll talk about FASCINATE-2 quite a bit. So the main poster for that would be the lipidomics poster. Yeah. So, what we showed this time was we reproduced... Yeah. ...and improved on the findings. Yeah. F rom the phase 2A, showing that lipotoxic issues are reduced by denifanstat, and changing also the composition of triglycerides to a more favorable one. Lipotoxicity is one of the three key drivers of NASH, and of course, denifanstat as we know, hits all three. But lipotoxicity is where it all starts. Yeah. So that was one of the posters goes without saying. Yeah. That increases our confidence. Yeah. In the phase 2b. The other poster was a preclinical work looking at semaglutide and a FASN inhibitor in, mice and... Yeah. ...in the obese mice, showing that the combination is better than the parts knowing that the number of patients on GLP-1s coming into NASH study is going to increase considerably. That, in our opinion, is a valuable finding as well. Thank you. Is there - h ave you guys had a chance to look at how much GLP-1 usage is present currently in your FASCINATE-2 study? We haven't disclosed that information. Okay. But what I can tell you is, in conversations with our advisors... Yeah. ... they're saying that they expect the GLP-1s to be in about 50% of patients... Oh, wow. ...entering NASH trials. Okay, now, at this junction, given that it's... Yep. ...the uptake. Perfect. Would love to kind of now dig in into FASCINATE-2. Sure. I think obviously the readout is expected in 1Q. I think you're gonna share the histological findings from the study. So I guess the first question that everybody has to ask is, as we head into the data, what would be considered a positive signal to warrant moving forward into a phase 3? So if you could talk about what, in your view, is considered, you know, the bar for success across the, you know, NASH resolution and 1-point improvements. Sure. We have not, of course... Yeah. ...disclosed the assumptions... Yeah. ...in the protocol. What I can tell you is that we are powered... Yeah. ...well enough to hit the endpoints... Yeah. ...that we believe we'll hit. Yeah. Then have an end of phase 2 meeting with FDA. Right now, we have to hit one of the primary endpoints... Okay. ...either NASH improvement, or NASH resolution, or NASH plus NASH improvement. Okay. I think your question bodes well, though, and that is what would spur us on to phase 3, and I think the combination of hitting those endpoints is gonna be... Okay.. ...really important. Rod, is there a certain treatment effect size that you would want to see, or as long as you show statistical separation in one NAS or NASH resolution, warrants you to move forward? If, again, we have not disclosed... Yeah. ...treatment size. We are adequately forward... Yeah, okay. ...to have a good result. Okay. The other question that comes up is, the central reader that you guys are conducting, it's a central. It's a single reader. And there is also what we realize as you will be moving forward to a registrational path, you may have a pair or, or two pathologists reading it. So is there an opportunity, maybe not a top line, but at some junction, to maybe when you identify a second reader and then have the analysis done retrospectively with single and both readers? How do you visualize this? Because a lot of- Uh... The next question for investors after the Phase IIb data will be: What is the translation of biopsy results from Phase IIb to Phase III? Uh-huh. Going from a single reader to a dual reader? Sure. Several points... Yeah. ...to the question. The first one, and it's important, is a single reader result... Yeah. ...from the IIb is enough. Yeah ...for the end of phase II. Yeah. Of course, this is what we agreed upon... Yeah. ...with FDA. We can retrospectively look... Yeah. ...at the data... Yeah. ...if we elect to do so. When you have a single reader of the caliber of ours, and I can tell you... Yeah. ...Pierre Bidossef... Yeah ...France, probably one of the best... Best, yeah. ...in the world. Data that come from him are very solid. Yeah. For the phase III, as you said, about a panel... Yeah. ...and FDA encourages companies to discuss... Yeah. ...how a panel would look... Yeah ...the important thing is that at the start of the trial the panel... Yeah. ...is trained together. I see. So that they are in good agreement as to how to call a balloon hepatocyte ballooning... Yeah. ...and so on and so forth. No, that's very helpful. And team, I guess, the other question that comes up is, you've also been very vocal that you're utilizing the AI pathology HistoIndex to benchmark similar. Will that data be also available at the top line? Yes. How do you hope to make that translation between both the, you know, per-person versus AI machine learning? Sure. The data, yes... Yeah. ...we'll be releasing AI pathology... Yeah. ...with a HistoIndex. The correlations can only go to a certain extent... Okay ...because of the way the platform is... Yeah. ...we gain that beautiful quantitative assessment of response that is not possible with a human. You can have an idea about the stages... Yeah ...but also they don't quite overlap with the nature of how the data are analyzed. Yeah. But they do add to the... Yeah. ...pathologist, and they bring back to your question... Yeah. ...about the phase 3, those data will... Yeah. ...bring more, even more confidence into the translation to a Phase III. Okay, very helpful. Is there an opportunity to, I guess, my question is, post that readout, how soon could you actually - how much of the safety data set could you be presenting also at the top-line data to us? Sure. We'll be presenting the... Yeah. ...safety data. Yeah. As you may imagine, it's the... Yeah. ...top-line safety... Yeah. ...the key parameters. One thing we know about the drug is we don't have limitations. Yeah. We remain blinded to the Phase 2b. Yeah. But we do have, as we mentioned, an independent data monitoring committee, and that committee has assessed the study. They are completely unblind. They're completely unblinded to all data, safety, efficacy... Yeah. ...you name it. They've assessed told us, "Continue as planned, no signals, no issues. Then, I guess, how soon after the Phase IIb study would you be able to start engaging with the regulatory agency to discuss next steps? Sure. Once we have the results, we will work as expeditiously... Yeah. You know what I mean? Yeah. That word. Expeditiously. Expeditiously... Yeah. ...as we can to have a meeting... Yeah. ...as early as possible. We cannot commit to the timeline because the agency dictates... Yeah. ...the timelines... Right. ...not us. Okay. And then in terms of phase 3 design, I assume, you know, your plan is to be very much in alignment of other historical- Yeah. Phase III designs that we've seen. Very much so. Is there some thought process behind designing a study that... Oh. ...is different than what we have seen so far? We're thinking a lot. That's a very good... Yeah. ...we're thinking a lot.. Yeah ...of course, of the phase III. Yeah. The good news is, as you said, other companies, in particular, Madrigal- Yeah. They set a good footprint... Yeah ...for us to follow. We are... Of course, the thing about Phase III is you have the guidance. Yeah. ...from the agency that you have to follow. But roughly speaking- Yeah Those studies look very much alike... Yeah ...in size, duration... Yeah ...and all that. Yeah. So this is, it's good to come behind... Yeah ...and learn behind a successful Phase III and learn what worked, what didn't work. Yeah. No, that's great. And then, is there an opportunity to also... What we're seeing is that once companies initiate their phase 3, they also start a cirrhosis trial because that could be supplemented as an outcome. Would you be taking a similar approach, like sort of like a F2, F3 population? Plus a cirrhosis outcome study, that is? It's a good question. Yeah. That's the alternative... Okay ...approach that FDA... Yeah ...suggests to accelerate... Right ...outcomes in the end. Cirrhotics is part... Yeah. ...are part of our focus. Yeah. We have a hepatic impairment... Yeah ...study going on... and that study is important... Yeah. ...as part of the regulations... Yeah. ...to go into cirrhotics. Yeah. It's a population that we're definitely interested in. Okay.. It's high on our agenda to... Okay. ...to do that pathway. Have you guys had generated any data in cirrhotics so far? No. No. No, you have to have the hepatic impairment. Okay. Yeah. Oh, to have it completed before... Yes. ...you actually initiate the... Actually, to this point that you made, in cirrhotics, for registration you need outcome... Yeah. ...not histology. Yeah, right. Really, what you want to do is, am I okay to go? Yeah. Totally. Yeah. We expect to be... Yeah. Totally fine, and then you see how things move. Yeah. One important thing that we learned from different... Yeah. ...studies in cirrhosis is the patients do have a significant... Yeah. ...amount of fat in the... Yeah. ...hepatocytes, and you can bring that down. You can bring inflammation... Yeah. ...and so on and so forth. So, yes, it's a population that does make sense. It's a population that mechanistically does make sense for us. Yeah. Yes, it's high on the list. I think the natural question from investors upon FASCINATE-2 being successful will be. And it is around also the same time as we will be seeing potentially the first approvable of the first NASH drug in end of the first quarter. So I think the question comes up is: How do you hope to differentiate, right? Like, what is the differentiation that denifanstat brings? Let's say, let's take it under the assumption that another oral resmetirom doesn't get approved, and there are a couple other agents that are maybe slightly ahead of you. What is the differentiation that denifanstat would bring versus other mechanisms in this very large population? Not, I mean, not the- Right. The size of the big market. It's a growing population. Yeah. I mean, it continues to grow, and I think we owe some support for our friends that are sponsoring- Yeah GLPs, right? Yeah. I mean, certainly driving awareness and identification of these... Yeah ...of these patients. So I think your point-your question is a really important one, and, and I think what we bring to the table is a really unique molecule, right? I think you pointed out that it's highly differentiated. It's really the only one that targets fat inflammation and fibrosis independently. It doesn't rely on just fat reduction... Yeah. ...to translate into... Yeah. ...a downstream effect. I think what's really important about that is that we are the only fat inhibitor, right? Everybody else that has a product on the market... Yeah. ...is a fat burner or a fat oxidizer. Yeah. While we are extremely confident that our molecule can be... Yeah. ...a standalone therapy, it also can work very well... Combination ...as a companion... Yeah. ...as a completely separate mechanism for a companion approach... Yeah. ...to treating these patients that are almost certainly... Yeah. ...going to need it. Yeah. And I think that really should be highly effective... Yeah. ...to the scientific community as well as the investment community. Yeah. And, I think one of the things that, as you guys know, it's taken quite a bit of pressure on the- on many NASH stocks, as including yours, has been this continuous outflow of, you know, the GLP-1, and that the GLP-1 is gonna take significant market share. And obviously, you guys alluded to the preclinical work that you have, which is the synergy between your product. Right. And that, you know... Could you maybe talk about your discussions with physicians, and what you've learned at the liver meeting on why aren't the GLP-1 the answer for now, right? Because I think that is, like, such a misconception for many investors. But it would be definitely worth to tackle that. Yeah. So the two things, the two key things we learned was, one, come, our trial... Yeah. ...or any other trial, about half the patients coming in- Yeah. ...will be on a GLP-1. Yeah. That expectation tells you that they don't... Yeah. ...solve the disease. Yeah. Weight loss matter. Yeah. There will be some patients... Yeah. ...that will respond, but we were also told... Yeah. ...by our KOLs, that there will be a very large... Yeah. ...proportion of patients that need something... Yeah. ...that is NASH... Yeah. ...specific. Got it. Yeah, no, I think, you kinda hit it. I think the two main areas are tolerability. Yeah. You know, you're gonna have a very large percentage of population that are gonna be episodic on GLPs. Yeah. They're gonna go on them... Yeah ...for as long as they can tolerate them, then they'll go off of them. Yeah. It'll be very similar, I think, in many ways... Yeah. ...to a lot of weight loss medications that have existed Yeah. ...for the last 30 years. Yeah. While patients are on it, yes, they will definitely see fat reduction. There's little doubt about that, but they haven't been able to translate it into fibrosis improvement. Yeah. You know, the two main studies that have been conducted, and I know it's just a singular GLP part of the equation. Yeah. But semaglutide in 72 weeks, and basically, the population that we're evaluating showed zero benefit in fibrosis despite showing... Yeah. ...improvements in NAS and NASH resolution. And then, in the 52-week study that was just published by Rohit Loomba in Lancet last year, showed that if, you know, there was definitively. No improvement in fibrosis nor in NASH resolution... Yeah. ...in the F4 cirrhotic population. To date, the fat reduction hasn't necessarily translated automatically... Yeah. ...into, excuse me, into fibrosis improvement, which is, as you know... Yeah. ...the key to a... Yeah. ...successful medication. So I think we'll continue to see these medications used, and frankly, I think we all should be thrilled that they are. Because, again, I think they're increasing awareness. Yeah. Diagnosis and identification of these patients. Yeah. And then disease-modifying medications like ourselves or a THR Could potentially step in and really... Yeah. ...push these patients across... Yeah. ...the line to... Faster. You know, a better... Yeah. Yeah. Exactly. A faster, better clinical outcome. Yep. No, absolutely. Do you think now, as you guys are obviously awaiting data, we're getting this question quite a bit? Is that right now the guidance is 1 Q? Is there a point at which you plan on fine-tuning the guidance more narrowly and give, like, sort of a monthly basis, and we'll have data on this month? Is that- We are working as expeditiously... Yeah. ...as we can. Yeah. To really deliver data as... Yeah. ...early as possible. You may imagine a lot of data... Yeah. ...generated... Yeah. ...in a study takes time to become... Yeah. ...available. Yeah, to make sure that it's... We're providing a pretty comprehensive data set here. Okay. Right? I mean, it's, it's not only the human histology... Yeah. ...as you pointed out, but also the digital pathology... Yeah ...as well. As well as many of the NITs, I think. Correct. All of the key NITs. Yeah. That will be presented. Yeah. That is... Yeah. Is there a reason to also, given that the EASL conference is gonna be around the corner, potentially save some of the data for that? So we... Will the EASL be, or will there always be an opportunity to do both, yeah? Our goal is to present the data... Yeah. ...at EASL. And without a doubt... Yeah. There will be new data. Yeah. Given the sheer amount of... Yeah. ...the volume of data. Right. Yeah. That come from a IIb. Right. The key data will be the top line. Yeah. But, absolutely, there will be new information... Additional. ...at EASL and at other conferences... Got it. ...as we dig... Yeah. ...dig more and more. Okay. And then maybe, like, another question is, what is the current like, sort of cash... I don't have Tony up here, but the current cash, the cash runway, because I think the next step for a lot of company and for a lot of investors are, how do you think about partnership interest, partnering this asset at this junction or conducting a phase 3 on your own? Yeah, no, look, I think we've just reported our earnings for the third quarter. We're just a little bit over $100 million... Yeah. ...in cash. We've been very conscientious in how we're handling that, and we'll continue to do so. Our cash runway, it takes us out into the first quarter of 2025. But I think, as you pointed out.. Yeah. ...is with positive results. Yeah. As we anticipate with our IIb in the first quarter, we're going to have to go out and... Yeah. ...pursue financing... Yeah. ...to get the phase 3 started and keep the timelines intact. That's really all of the money that we generated from the IPO is... Yeah. ...with the exception of a very small subset we're developing for acne, is really dedicated to match and all the efforts to support that. So, will we consider strategic options? Absolutely. Yeah. You know, we're going to be very opportunistic as we as we pursue the best path forward. Our goal is to get this product out as quickly as we can. We think it would be highly invaluable to the community, and patients will benefit enormously, so. Great. Well, team, we have covered a lot. We really can't wait for the data, which is pretty, you know, imminent in the first quarter. We're wishing you the best of luck. Thank you. We can't wait... Thank you. ...to see it, and have a great 2024 as you have ahead of you. So I want to say thank you on behalf of all of us here at Piper Sandler. Thank you.