I'm very happy to be sitting here with Rohan, who's CEO of 89bio, and 89bio is one of the liver companies that we've been focused on for a long time in the area formerly known as NASH, now MASH. So, I think we'll start off, Rohan, if you can give us just an overview of 89bio so we can get everyone on the same page. Sure. Thanks for having us, Lisa. So 89bio is a late-stage clinical development company focused on liver and cardiometabolic diseases. And our lead program, which we call pegozafermin, it's an FGF21 analog, which we believe can be transformational in these disease states. Because the way FGF21 acts, it can have a very profound effect on liver as well as cardiometabolic diseases. We have demonstrated this in two distinct indications. One is NASH or MASH, as it's known now, where we had really positive phase IIb data earlier this year, and we are now getting ready to move into phase III development in the first half of next year. We also have a second indication, which is severe hypertriglyceridemia. So this is patients with triglycerides above 500 mg/dL, so very high levels of triglycerides, and there we are already in phase III development. We announced really good phase II data last year, and based on regulatory input, we initiated a phase III study in the middle of this year, with top-line results from that phase III expected in 2025. One highlight is yesterday we put out new data from our phase IIb study in NASH, which was a long-term extension in that study. Our primary endpoint was at 24 weeks, which is the data we put out earlier this year, and yesterday we announced data from 48 weeks of treatment, again, in a blinded phase, which showed really good, robust, and consistent response all the way through weeks 48, with a really nice tolerability profile. This becomes important when you think about NASH, where you're going to be doing long phase III studies, and more importantly, a chronic condition, you want to see sustenance of response as well as good tolerability. So we just wrapped up the Liver Meeting not that long ago. I think it was the last week. A couple of weeks ago. Two weeks ago. Yeah. It's all a blur now. What, what were some of the key takeaways from the Liver Meeting, from your perspective? Sure. I think so I think one thing was, I think in NASH, MASH, there's been a lot of progress made over the last couple of years. I think we've learned a lot more about this disease state, and now you're seeing data from late-stage programs, right? And potentially, the first drug could be approved next March. So there was a lot of buzz about finally, we're getting a drug to market, and this has been a question which I always get from investors. Like, no one's actually proven that in phase III, you can get across the finish line, and we are getting to that stage. So that was one. Clearly, there was a lot of interest in the FGF21, because a lot of the experts and clinicians are looking at FGF21 as a class of drugs, which could really make a difference to these patients, especially those patients who are advanced fibrosis, like F3 and F4 patients, which are cirrhotic patients, because you want really a highly potent anti-fibrotic. And it, it was very clear everyone is focused, at least in the expert community, on drugs which have a very profound impact on fibrosis. I think the third theme is, no surprise, a lot of discussion is how are the incretins or the GLP-1 therapies going to impact the space, right? And our take was, people go, "Look, these are good drugs." They, because a lot of these patients have obesity or diabetes, and these drugs will be used, but the GLP-1s are not a cure-all for NASH. There's a lot more to NASH than just managing diabetes. And then, more importantly, I think in some of the presentations, they talked a little bit about how those drugs are going to work peripherally, and you're probably going to need liver-directed drugs. I would say those are the kind of the main ones. A lot of talk on the transition of the name from NASH to MASH. Yeah. That's going to be interesting, but it looks like that train's left the station, and over time, I think everyone's going to be calling it MASH. I think you're right in that there was a lot of... Of course, there's been buzz about GLP-1s for the last year, and it's kind of unfortunate timing, because we've finally made so much progress in MASH. But to your point, you know, that category hasn't yet shown a benefit on liver fibrosis- Yeah ... which is sort of the holy grail of MASH treatment. Yet next year, there's going to be some important studies reading out. You know, how important do you think-- You know, for example, for tirzepatide- Sure There's going to be data for, you know, in MASH, and I think actually some longer-term semaglutide data as well. How important are those readouts for kind of like, you know, investor interest in space? Maybe we should take a poll of the room. I don't know. But, like, how are you seeing, you know, that, Sure ... potentially impacting, the value? So I think it's an important data point. I mean, as you mentioned, so semaglutide has done large studies in both pre-cirrhotic F2, F3 population and in the cirrhotic in F4, and in neither of those studies were able to demonstrate improvement in fibrosis. Very nice NASH resolution numbers. Not surprising, given the impact they have on diabetes and weight. I think the tirzepatide data, again, the feeling, at least in the expert community, is it probably will work on NASH.... but the jury is out whether it'll have an impact on fibrosis, because, again, like the GLP-1s, so we should talk about meaning from mechanistically, there are no GLP-1 receptors on the liver. So the premise is a lot of the activity taking place on the liver is happening indirectly. Similarly, there are no GIP. That's also a incretin which acts in the gut, right? So the question is whether that will impact in a short time period of 48 weeks the liver. Now, having said that, I think it's an important data point because utilization of these drugs continue to rise. And so when we think about our drugs, like an FGF21, where we have shown very nice data on top of the GLP-1s, we recognize that a lot of these patients are gonna come into the office on an incretin therapy, and but we are showing that on top of these patients who are in stable doses, we see benefits on whether it's liver markers, whether it's fibrosis markers, et cetera. So the feeling is, look, we'll understand the data. It will inform how we think about additional development. But the case is these drugs could work, but they're not curing the disease, right? I mean, even if you have a 25% fibrosis response, that means 75% of patients are not responding. When you think about the late stage, the other dimension I would bring out is when you think about late-stage NASH, you really want a drug which is going to act pretty rapidly on the fibrosis component. In earlier stages of NASH, Lisa, physicians will say, "It's okay. I can take 2 years, 3 years, 4 years to impact their NASH." Once you get into phase 3, the clinician's whole goal is prevent progression to cirrhosis. I can't take the risk because once you cross that bridge into cirrhosis, it's really bad for the patients. And then, once you're in cirrhosis state, you want to prevent decompensation, because once you're in decompensation, unfortunately, it's 6-12 months, you're into a liver transplant or some kind of really bad mortality outcome, right? So when you're in that stage, what the clinicians are saying is, "I'll use a GLP-1, but I need something more dramatic or more, like, directed at the liver." So long answer is, look, we're looking forward to seeing the data. I think it impacts the field, and you know, to us, it doesn't change the overall landscape for additional therapeutic options required for NASH. So you're really honing in, it sounds like then, on this sort of F3 population. Is that, is that fair to say? We think our trials will be F2, F3, but we think the sweet spot for an FGF21, which is a good antimetabolic and a very strong antifibrotic, is that advanced fibrosis patient. And then, clearly, we think there's a huge opportunity in the F4 cirrhotic population. We've shown some promising data. The other FGF21 has shown some promising data, and we think that's a market where really the FGF21s are most likely to be the most successful players, you know? I mean, it's the highest unmet need. Let's just dive into that. Now I'm gonna push that question up in my, in my mind here. Sure. So the cirrhotic population, there were some, you know, I guess, somewhat disappointing data, in fact, right, from one of the other FGF- Yeah ... 21 players out there, namely Akero, and you know, the stock took a big hit. You know, what is your take on that data, and what does it mean for your program? Sure. So, I think you're referring to the SYMMETRY data- Yeah ... which people might be familiar with, with efruxifermin. So just to remind the listeners, so efruxifermin is an FGF21 agent, analog, sorry. It's a different technology. It's a fusion protein. Ours is a glycoPEGylated version of FGF21. Very similar data from an efficacy perspective observed across the spectrum, whether it's F2, F3, or F4, but differences in tolerability in the two drugs and differences in dosing regimen. That's a once a week. We had a once a week, once every two week drug. So they announced data from a really good study, close to 200 patients in F4 cirrhotic patients, and they missed their primary endpoint, which was a reversal of fibrosis. And it clearly cast a black cloud about over the entire category. When we take a look, Lisa, at the data, we actually think it's very encouraging data. And I remember having a conversation with the KOL, like my CMO and myself, like we were sharing the data, and we were like: "We'd love to talk to you about this failed study." And the first reaction was, "That was not a failed study. That was the best F4 data any drug has shown to date." So why do we say that? When you look at the totality of the data, not just that one primary endpoint, we think it was very compelling. NASH resolution numbers were good, all the biomarkers looked good, all the non-invasive tests looked good. And so from our perspective, our external lens, is it actually supported the premise that FGF21 could be active in an F4 population. I think the question in this case was, it was a study done for nine months. Is nine months long enough to show a reversal of fibrosis? When we had talked to all the experts, even prior to the study readout, they're like, "F4, you want to be 24 months. You want to run a long trial." And then the second was: Was it adequately powered, right? So, our take from that data set was actually we took a very different lens. We know it's investors had a different view of it, but from a pure drug development perspective, we think it's a powerful data set to suggest that FGF21 could be incredibly potent and really help these patients. Yeah, one thing I've been contemplating, like, duration, you know? Yeah. On one hand, I can see longer, you know, longer duration, maybe better results, but also does the disease catch up? I mean, would you maybe start to lose effect over a longer duration? I don't know. I mean, you're pretty advanced disease when you already have cirrhosis. Sure. Curious. So it's a very fair question, right? What is that right balance? I'll make two comments. Why longer duration? So think about an F4 patient. It's probably taken them 15 years to progress to that stage. Their fibrosis matrix is a very dense matrix, okay? As distinct from an F2 patient who might have got there in two to four years, right? So to break down the matrix, you need a much longer time period, and you also then need a longer time period for the liver to heal and regenerate. So from a biology perspective, this is why even before the study read out, the experts were, F4, you want to give it a longer time, right? Your other question is, how long... Like, if you go too long, is something else happening in the body? If you are addressing the underlying issues which are causing NASH, which is the steatohepatitis, the diabetes, the obesity, you're keeping those in control, so you're stopping the insult to the liver- Right. Then it is okay. If the liver insult continues, you're absolutely right, right? Because it's a leaky bucket. If you're continuing to have insult to the liver and you're working on the fibrosis, it will keep... It doesn't get better. And this is where I think FGF21 is unique, because we are addressing the underlying core of the disease, which is the metabolic dysregulation. So if you were just doing something on fibrosis but not impacting the underlying metabolic dysregulation, it could be problematic. We think that's the benefit of something like an FGF21. How are you thinking then about your Phase III program? Let's start with cirrhotics, and then we can move to kind of the F2, F3 population. You know, resmetirom is doing an outcome study in cirrhotics. Yep. There was a thought that maybe, you know, some other companies might try more of a biopsy endpoint. Is that still in play now that we've seen that data, or do you think you'll go down the path of doing an outcome study? Then maybe we can talk about your phase II, III. Are you going to do a standard kind of- Standard. resmetirom-like study or some other twists you can put in there? How, how are you thinking Sure. about your phase III program? So these, as we've shared publicly, we are in the process of finishing all our regulatory discussions, both with the FDA and EMA, on both these studies. And by the end of this year, we will have clear guidance based on what the regulatory input is on both these programs. So in the next few weeks, you will hear exactly the specifics. But conceptually, here is where we are. We are looking to do two phase III studies, one in F2, F3, which is arguably the more classic study you would do. And that's an important study because you can get accelerated approval based on histology and get to market, right? We want to bring this product to help patients. I think the second study is in the F4 patients, which today the guidance document requires you to do an outcomes study in the U.S. Interestingly, in Europe, the guidance document has always kept the door open for discussions on using histology as a basis of conditional approval or the, which is the same as accelerated approval. And we look forward to having those discussions, you know. Okay. The symmetry data does not scare us, to be honest. Good. I mean, I actually thought the magnitude of benefit, I would agree with you, was actually quite good, and- Yeah ... if you had powered it, you might have gotten a different outcome. But Phase II studies aren't always meant for that purpose. But, okay, I want to, I got a lot of questions on, like, why you're pursuing SHTG. So why are you pursuing SHTG? So, there's a couple of things I would say. One is, it is a large market which still has a very significant unmet need, okay? There's over 4 million patients with SHTG. About two million get treated, and about 1 million of them are unable to bring their triglycerides below 500, despite being on medication. So which is the fish oils, the statins, the- But there's a nice pipeline coming along- So- ahead of you, even. So- So, let's talk about that, right? So the pipeline is the APOC3 drugs, right? We think FGF21 offers something very different and unique. So when we talk to clinicians, what they say is, "We want something which does more than drop triglycerides." Reducing triglycerides is important, but these people all have liver fat. They have glycemic control issues. 70% are either prediabetes or diabetes. The APOC3 drugs do nothing on liver fat, and they do nothing on glycemic control. The third thing I will say is, so this was recent data from Arrowhead's APOC3. In their data set, when you look at the placebo-adjusted triglyceride reduction, it's not that much better, and they had a whopping 59% increase in LDL. These are patients at a high cardiovascular risk. Yeah. I just wonder whether a physician is going to put someone on a drug which is going to actually take their LDL up. We kept LDL flat. Okay. Okay? The last thing, and they also had 20% had glycemic control issues. So I think the drugs—now, if someone's triglycerides are 1500 or 2000, your primary goal is drop triglycerides. All this other metabolic benefits is not as that important. But the sweet spot of most patients are triglycerides in that 800 ±. That's where we think it is. I think the second thing I would say is, in the last 30 seconds, is—it's a de-risk program. The endpoint is reduction in triglycerides from baseline for full approval. We've got that in writing from the FDA. Our phase II data was incredibly compelling, 63% reduction in triglycerides. So it gives us a second de-risk program, and there is a lot of leverage we get from NASH. Great. So just quickly, in five seconds, what can we look forward to next year from 89bio? I think the key ones is the initiation of our phase III programs in NASH and continued execution on the severe hypertriglyceridemia program. Excellent. Thank you so much. Sure. Thanks a lot, Lisa.