Good morning and welcome to Evercore ISI's Healthcare Conference. My name is Liisa Bayko. I'm one of the SMID Cap analysts here, and I'm joined by 89bio and Rohan, the CEO. We've known each other for some time, and really excited for you to be here. Why don't you start with a quick overview of 89bio? Sure. So we are a late-stage clinical development company focused on liver and cardiometabolic diseases. Our lead program is pegozafermin, which is an FGF21 analog, which we believe can be transformational in these disease states. We are studying pegozafermin in two distinct indications. So we have two phase III trials in MASH, one in pre-cirrhotic F2 and F3, and that study initiated earlier this year. And then we have a second study in the cirrhotic population, which also initiated this year. And in both these studies, there's two shots on goal. So based on histology, we hope to get accelerated approval in both these indications in the U.S. as well as in Europe. And then we continue these patients for outcomes to get full approval. We also have a second indication in severe hypertriglyceridemia, which sometimes gets overlooked, but we're pretty excited about it. This is patients with triglycerides above 500 mg/dL. It's a huge market with an unmet need. And there we have a phase III study, which is projected to read out in 2025. So it's exciting that we'll have our first phase III readout next year. It's a biologic drug, which is given once a week or once every two weeks, and it's presented in a liquid prefilled syringe. So it's pretty convenient for patients. And this is important when you think about patient convenience. And what we've seen is a pretty nice, well-tolerated profile to date. Last one I'd close out is kind of where we are from a cash position. We recently did a financing. So if you look at the pro forma cash, we are at $565 million approximately. Proforma cash is what we're sitting at today. There's always been a lot of controversy on the MASH market, and now we have Rezdiffra. So kind of any insights, perspectives on how that launch is going, what it says about the market? Look, Liisa, we've always believed there is a market here. I know there's been some skepticism. Is this actually going to get commercialized? We fundamentally believe that there is a huge commercial market, and I think the Rezdiffra launch is showing it, right? And it's not just the fact that they've exceeded the consensus estimates. It's just looking at the payers are willing to cover it. Payers are not requiring a biopsy. That was a big question, like, is that going to kill the market? But then you also see the penetration they're getting across and the breadth of physicians who are prescribing it. When we talk to physicians, whether it's experts or we do our pulse survey with GIs and hepatologists, the intent to treat numbers remain incredibly strong. Maybe you can speak to sort of where do you see the role for FGF21s in the MASH market? You know, we have Rezdiffra. There are other molecules coming. We have obesity medicines, which address some of the fat in the liver as well. So what role do this class of drugs play? We think the sweet spot for pegozafermin is in the advanced fibrosis patient population. This is primarily the patients with F3 disease and with compensated cirrhosis. Let me explain why we think that. When you think about MASH, it's a progressive disease. In the real world, physicians are not going to biopsy and say, "You're an F2, you're an F3." They're going to look at what is the risk profile of these patients, right? And they categorize it into kind of low, medium, high risk. And if you think about it, if someone is a low-risk patient, which is more like that F2 patient, the physician's treatment objective is to resolve the steatohepatitis. However, once they progress and they become high risk, the treatment objective changes from resolving steatohepatitis to prevent the progression to cirrhosis, prevent the progression of fibrosis. So if you think about that construct, Liisa, if your goal is to resolve steatohepatitis, you can use a good metabolic drug. Someone can be in an F2 state for 10 years, right? Address their underlying disease like diabetes, obesity. But once you are advanced and your treatment objective is to prevent progression of fibrosis, you want a really potent anti-fibrotic. And that's what's unique about FGF21 and pegozafermin is we not only work on the metabolic pathway, we are incredibly effective as a potent anti-fibrotic. And so that's where we think the sweet spot for us is that advanced fibrosis. And then in the cirrhotic market to date, the FGF21 class seems to be the class who has shown a benefit, right? People have tried. It's a tough disease to treat. And we're pretty optimistic that FGF21 and pegozafermin is going to show a benefit in that. Having said all of this, we acknowledge that people are going to be on GLP-1s. Incretin therapies are going to get used. We see that more as backbone. People are going to be on these for their diabetes, their obesity. It doesn't faze us because we are showing really good data with pegozafermin on top of GLP-1s. So a lot of these patients will be on GLP-1s, but we've seen it in our own study. They still progress and they end up with F3 and F4. So we think we coexist very well with that class of drugs. But the sweet spot for us is this advanced fibrosis patient, which we think we can come to dominate. So that brings me to my next question. I want to talk about the upcoming Akero data. It seems like that would be really important visibility for you as well, because we'll be looking at long-term data in this compensated cirrhotic population. What are you hoping to see in that data? We know when we saw the earlier data point, it didn't quite, you know, kind of theoretically reverse fibrosis, but there were some trends there in, or reverse cirrhosis, sorry. So what are you hoping to see in this data? What would be encouraging? What would be disappointing? Maybe you can qualify that. Sure. So Liisa, when we saw that data, I think we had maybe a slightly different take than the investor community. We actually thought it was solid data. It actually built the case that FGF21 as a target can actually impact cirrhosis patients. And I say that based on the totality of the data. Yes, it missed the primary endpoint, but it was never powered for a primary endpoint of 10%. And I think the study was too short at nine months. We think at two years we should see a widening of that delta. We'd like to see that that delta went up. When you ask any of the experts, they'll say a placebo-adjusted delta of 10% is clinically meaningful. If you had 12%-15%, that's really good, right? And so if we see a widening of the delta, that'll be important. Clearly, obviously, you'd like to, all of us in drug development, want to hit stat-sig. But I think we also want to see what the totality of the other markers look like, because in some ways that will inform us about how to power your study in phase III and how do you think about some of the endpoints you're looking at in phase III. Our phase IIIs have just started. So we have the flexibility based on what we see in the data to make any adjustments. So I think from a development perspective, I think that's going to be incredibly important. Understanding the tolerability of the drug, we think there is a difference between pegozafermin and efruxifermin on tolerability. I think we're going to get some more data from this. So clearly, you know, it's an exciting time for the category. It's exciting for FGF21. Our gut is we should see good data, right? All the markers would suggest, you know, we've done 48 weeks in the F4 population. We've seen a maintenance of benefit across all the liver endpoints, and what you would expect if you dampen and maintain the injury and insult to the liver down over an extended period, you should see a benefit on histology. What kind of threshold? We've heard different numbers thrown around, like a 15% delta or this, that, and the other thing. We also know there's going to be a lot of patients discontinuing. How do you think about how to really interpret the data? So again, I'll go back to, I think what in a phase III setting, a 10% would be viewed as clinically meaningful. A 12%-15% would be viewed as this drug will get broad utilization. Now, I think in their study, obviously, with a bigger N at 10%, it was not stat-sig, so it's not going to be at that. I would encourage us to look at what does this mean from the likelihood that your phase III study is going to be positive, because the phase III studies, we are powering it pretty adequately, right? Because the one thing which I think will be important to see in this data set is they had a placebo response of 14%. When you talk to some of the KOLs, as I talk to them, they go like, the likelihood that in a cirrhosis patient population, after two years, you will see that higher placebo response will be very rare. Because unlike an F2 patient who can stay in that disease state for a long time period, cirrhosis patients progress, unfortunately, right? So I think that's a couple of the dynamics, because 14% is pretty high, you know, for a two-year study. So we just saw each other at the liver meeting, and there was some really interesting data there from Boston Pharma. So my point is there are several FGF21s now emerging, right? This is a very interesting target for this disease. There's yourself. We've talked about Akero. Boston Pharma came up with their once monthly. We have one from Novo. I think we know a little bit less about that. Where do you see how you're differentiated from those? And, you know, I guess any comments on the new data from Boston Pharma and how that positions them with the once monthly? Be curious on how you see the distinctions between these molecules and what that might mean ultimately for the commercial opportunity. Sure. So let me start at the category level, and then let's talk about specific differentiation, right? Our perspective is if FGF21 as a class lives up to its promise, we think the category is big enough that there's going to be multiple FGF21s who could be incredibly successful. So if you look back at other therapeutic areas in large markets, multiple classes of drugs do really well, right? Meaning you're seeing it in GLP-1, right? And you have Ozempic, you have Mounjaro, but Trulicity is yet selling multi-billion dollars, right? You look at all the immunology drug classes. If you have a target which is incredibly good, you have multiple drugs who can become blockbusters. I genuinely believe that could happen in this space because based on the data to date, FGF21 as a class looks like the best class. So let's talk a little bit about the differentiation, right? And then I'll come to the Boston data. Each one of these drugs has taken a different approach to extend their half-life. So we have glycopegylated the version to increase the half-life, allowing us to deliver it once a week, once every two weeks. efruxifermin and the Boston, they've used a fusion protein backbone. And I think some of the differences you see might be related to the structural elements. Now, if you look at the efficacy between, say, us and efruxifermin, I would argue it's very similar. So at week 24, both of us saw about a 20% delta, placebo-adjusted delta. Boston saw like in the same range, like early mid- 22 or 23, but in a much smaller sample set, right? It was, and with a very high discontinuation rate, which is very confusing when you have a 28% discontinuation rate. However, on tolerability, we see a very different profile. We see pegozafermin tends to have much lower AEs consistently on the GI AEs relative to efruxifermin. We have not, with pegozafermin, seen any significant or clinically meaningful changes relative to placebo on bone biomarkers or DEXA scans, so we think there's a little difference in the tolerability. It might be associated with the structure of a pegylated version versus a fusion protein versus efruxifermin; we have a differentiated profile in that we are giving it once a week and once every two weeks versus a once-a-week drug, and I think this is important, and here Boston Pharma has once a month, and this is important in a chronic disease state. Patient compliance is often driven by convenience, and that becomes important. A third very interesting differentiation is we are a liquid product in a prefilled syringe. efruxifermin is a lyophilized drug, and as I understand, Boston Pharma is a lyophilized drug. Per se, that's not. You got to reconstitute it. You can inject it. But if you think from a life cycle management perspective, one day you might decide you want to have a co-formulated product with a GLP-1, something Novo is looking at. You mentioned Novo. pegozafermin could have a potential to be co-formulated. I'm not sure how you co-formulate a glycopegylated. I'm not saying it can't be done. Sorry, how you co-formulated a lyophilized tablet with a liquid, right? And then the last differentiation is I think the fact that we are developing it in two distinct indications in a commercial setting is going to be a significant advantage. So a lot of MASH patients are sitting today in endocrinology and cardiology offices. With the SHTG indication, we're going to be able to leverage and have a presence in these treating physician offices besides just the GI and Hep, right? So having multiple indications, and again, I'll go back to other therapeutic areas, the synergies you get from it and the halo effect you get from having more than one indication actually helps build your presence. So again, I'll go back to, I think FGF21, we can be successful, Akero can be successful, but we have a very differentiated profile. The Boston data to answer your question, it's a small data set. I think we need to learn a lot more. I am intrigued that they, you know, in the active drug arm, they had like a 26 or 28% discontinuation rate, which makes it a little difficult to interpret the results. And they had a very high placebo rate. So it's, but it looks like the drug works. The AE profile still continues to be, when you look at the GI AEs, you know, you're yet talking in the 30% range, similar to efruxifermin. pegozafermin tends to be more in the teens. So I think we still have, and then finally, I think efruxifermin and pegozafermin are significantly ahead. I don't know whether it's a year ahead or probably two to two and a half years ahead, which puts us at a very different position. You know, the two of us, I think, are going to be the market leaders. Are you working on an autoinjector? That is part of the life cycle plan. Yeah. Okay. Would that be for initial commercialization or kind of a next generation? It'll be the next generation. Okay. Yeah. The initial commercialization will be in the prefilled syringe, but we're using a very standardized Becton Dickinson prefilled syringe, which can work with pretty much most autoinjectors. Do you see an opportunity for cryptogenic cirrhosis for the FGF21 class? Because that could be, you know, a whole other part of the market that we haven't really considered. Yes, so we have elected in our phase III not to include cryptogenic. The only reason there could be a role for it, okay? I think the reason is you don't know. I mean, cryptogenic is basically you don't know what's caused it, right? People are saying there could be MASH because historically there was a MASH diagnosis. I think we decided not to include it in the phase III because we did not want to mix up the data. I think there could be absolutely a role, but we'd like to potentially study that in a separate cohort. That makes sense. As distinct, like, from confounding your data in your phase III, and then you're like trying to scratch your head, like, you know, what happened? Okay. Just a couple of words on your strategy for SHTG, because you're going to have that data actually relatively soon, and then you'll kind of wait. That'll be, how do you kind of get that indication when you have the MASH program going? Yeah. So we have said MASH is our priority. We think that's the bigger indication from our IRA perspective. We think that's what we want to lead with. However, we think there is a significant market opportunity for SHTG, okay? What we want to do is, Liisa, have a discussion with the agency whether this single study would be adequate to support a supplemental BLA filing, right? If SHTG was the lead indication, we know you require two studies. But in a world where you've already got an indication for MASH, you've built a large safety database, because with the MASH trials, there's going to be a huge safety database. If we were able to get the regulators to align that a single study is adequate, that really puts us in a very advantageous position, right? Because at that point, we don't need to spend any more money. We've already expended the money against it. If the agency requires a second study, we would figure out what's the right timing to do the second study. But strategically, we see SHTG as a supplemental BLA, you know, to support and expand the MASH indication we have. Okay. And as we sort of wrap up, because we're getting close on time, maybe you can just talk about your cash runway. I know you recently raised some more money, so that's great. How far does that take you? And walk us through kind of what's in store for 2025 for 89bio? Sure. So what that cash takes us, it takes us past our SHTG readout next year. And it takes us much closer to the readout from the MASH programs, the histology portion. It doesn't take us all the way till the readout of the histology portion of the MASH. So you can say well into 26. The key ones for us next year is the SHTG readout in phase III. And then it's more about the enrollment, you know, and how we are tracking on the two phase III studies of MASH in 2025. Excellent. Well, thank you so much. Cool. Thanks, Liisa. Thank you.