Thanks, everyone, for joining us. I'm Andrea Newkirk, one of the Biotech Analysts here at Goldman Sachs, and I'm really pleased to be joined by Andrew Cheng, President and CEO of Akero. Thanks so much, Andrew. Thanks for having me. Maybe at a high level, let's start with where the NASH field is now. We've obviously seen a lot of development, both on the clinical development side with the first commercially approved drug last year. What makes you so excited about the forward path in NASH, and how do you see Akero as best positioned to take advantage of that? You know, that's a great question. What we'd see is that, and this is hats off to the Madrigal team and their CEO, Bill Sibold. He got the first drug approved last March of 2024, and you know, it really speaks to the medical need and how well that drug has done. As a result, there are many challenges that were, I would say, investors' pushback on the NASH field, but have really been addressed by that. What's so exciting is that, you know, we'll talk about this a little later, but in January, we really had some F4 data that was really a first of its kind. We were lucky to have a simultaneous publication in the New Journal of Medicine last month, along with a podium presentation at Late-breaker at the European Association for Liver Disease. We're really excited about the opportunity to not only address the pre-cirrhotic population with past data, but the new data in the cirrhotic population, which has really been difficult to treat to date. Yep. About FGF21s, how does efruxifermin differentiate from pegozafermin? We also saw Boston Pharmaceuticals' efimosfermin, which is now GSK's, but how is efruxifermin differentiated? Efruxifermin is a fusion protein, an Fc fusion protein, so it's fused to the Fc portion of our IgG, and in that is similar to the Boston, former Boston, former Novartis, now GSK compound following the acquisition in May. Yet on the other side, it's a dimer, so it's a divalent or bivalent compound, so there are two FGF21 attached. What's different about it is that, unlike the other two agents, there have been important modifications at the C-terminus. What I mean by that is that FGF21, in order to be active, requires a trimeric interaction. That is, that there's a binding from the C-terminus to this co-receptor called beta klotho. It's that binding that regulates the activity, and there's a natural endopeptidase that cleaves that residue 171, and we've made, or Amgen because we're an ex-Amgen compound, made modifications to that to enhance the binding. Therefore, the longer it is tethered to the co-receptor, it is better able to bind to the N-terminus domain to the FGF receptor. I know that was a long answer, but the short answer is that the pegozafermin is a pegylated single-chain FGF21, and it does not have, we are the only one with that modification and some of the other modifications at the C-terminus. That is the short answer. Great. What do, maybe what do those modifications really translate to as you start to think about the efficacy profile? Sure. They translate to better kinetics at the binding, mostly in the dissociation context. We've done some in vitro work, but really what they translate to is, quite honestly, some of the best clinical results we've seen in the field, both in the pre-cirrhotic and in the cirrhotic population that we've touched on. The cirrhotic population I mentioned earlier, we're the only company, FGF21 or any other mechanism, to demonstrate one-stage improvement of fibrosis in cirrhotics ever. Unfortunately, the patients have very few options there, and for us to be able to demonstrate is an important milestone for patients with cirrhosis. Similarly, we've seen in terms of one-stage improvement in cirrhosis, excuse me, in the pre-cirrhotic population, we have about a 75% one-stage improvement of fibrosis with roughly a 50% effect size over placebo. Again, that dwarfs the competition in the field. Let's start with the cirrhotic data that you just presented in January. It's first very large, first large data set in this patient population. Maybe talk to us about what you saw between week 36, week 96, what that could imply if patients were to stay on even longer. What kind of effect size could you see? I think that's a great question. To recap the data, we showed at week 36, we showed roughly a 10% difference between active and placebo, which was not statistically significant. At week 96, 60 weeks later, we saw roughly a 25% difference, roughly 39% versus 14% for a 25% delta. What's important about that is the principle, as you just highlighted, that longer dosing matters. We saw this principle in the pre-cirrhotic population too, so it's very internally consistent. We saw roughly about a 20% effect size in pre-cirrhotics at week 24. At additional 72 weeks, then we saw 75% one-stage improvement of fibrosis or a 50% effect size. The effect size more than doubled from 20% to 52%, and then in cirrhotics, it went from 10% to 25%, again, more than doubling. We're very excited, and when you think about long- term, unfortunately, even though we're the first of its kind to be statistically significant and a 39% improvement, unfortunately, it means that 61% of the patients didn't see an improvement by two years, but we believe with longer dosing, they can see that benefit. Do you expect that a plateau will be reached at some point, or could you continue to see improvement over longer durations? Very difficult to say for sure, but based on what we've seen from both the pre-cirrhotic and cirrhotic populations, it's not clear that there will be a plateau, primarily because the compound is very effective at shutting down new collagen synthesis. Remember, a fibrotic burden or collagen is a balance between the rate of new collagen deposition and degradation. Because we've sort of shut off synthesis and degradation is ongoing in the background, one could see over time, even the greatest fibrotic burden potentially could get reduced. Do you have a sense or an understanding of why some patients may take longer to respond here? Because you are seeing a deepening of that response over time, which implies new patients, and I think you've shown some data to that effect, but what distinguishes a patient who's kind of an early responder versus one that takes a little bit more time? We're still digging into that, but on fresh, what it appears to be is that there's a range of collagen burden. Cirrhotics, unfortunately, some of them may have as little as 6% collagen burden in their liver. Some may have as high as 35%. We think that the people who respond the soonest are those with the smallest collagen burden. As you think about your phase III, I mean, that's a great segue, but as you think about your phase III and the patients that you're enrolling, are you, talk to us about your inclusion criteria then to that effect? Sure. You You can imagine that as we go to phase III, we're trying to leverage the learnings that we have from our phase II- B study. When we look at the people who responded, those 39% of people at the 50 mg dose, we're really sort of reverse engineering and looking at what they call predictors of success. What are those characteristics for those patients, and how can we translate that into the inclusion criteria into phase III? That is what we're actively doing. Also, keep in mind that there are two cohorts. All patients will, in phase III, be followed for outcomes, but there's a subset of patients that will get a second biopsy. In terms of who should be in cohort one and be followed for outcomes, or who should just be followed for outcomes, we're trying to redirect and enhance those populations for success. Got it. That's interesting. Maybe just one question on VCTE, which was also another measure that you reported here. How should we think about the magnitude of benefit you saw there relative to, say, Madrigal, who also reported a VCTE improvement? You're referring to some data that over the, in that, on the 50 mg dose in SYMMETRY, what we saw is roughly a 7.3 kPa decline, average decline in VCTE, and what we saw compared to with the Madrigal data is roughly 6.7 kPa. Of course, whenever I make this kind of comparisons, you always say comparisons about cross-study comparisons are fraught because not exactly the patient baselines are exactly the same. At the same time, they're in the same zip code. What we'd say is that we're no worse. When we look at some of the other metrics that Madrigal put out, they commented that 52% of those patients had a 25% reduction. If you look at that as a threshold, in our comparison, the number of patients that had a 25% reduction was 70%. Again, numerically greater, but probably not outside the zip code. What is more meaningful as you try to assess the benefit of a drug? Is it VCTE? Is it the one-stage improvement per biopsy? How do we think about those two endpoints? I think when we look at it, the biopsy is, of course, the issue because the medical expression, the issue is the tissue, so you're absolutely certain what's going on. At the same time, recognizing that there are only so many portal tracts in a small biopsy out of a 16-gauge needle, and that the liver is the largest solid organ in the body. The question is, VCTE is also very helpful because it gives you a totality of the data. The best circumstance is no one metric or measure is ideal, and you would look at the totality of the data and seeing the changes that you see, but also that's corroborated by a non-invasive helps really marry those two data points together to give physicians and patients confidence that the drug is doing what it should be. Got it. Multiple endpoints to get a better idea. Correct. As you think about the safety profile here, you did have three hepatic decompensation events that happened to be in the treatment arm. How should we interpret that finding? Yeah. So I think a lot of investors have asked me about that at this conference, and some of it has to do with what they're trying to understand because phase III has an outcomes basis for liver events. The liver events are, so we're clear for your audience, ascites or esophageal varices or hepatic encephalopathy or all-cause mortality. When one takes that lens and sort of looks backward into phase II, what we saw is that the actual balance was that we had, unfortunately, a patient died of pneumonia on the placebo arm, and then we had two patients with ascites, one on 28, one on 50, and then we had one patient on 50 having hepatic encephalopathy. The breakdown, if you were using the phase III lens, would essentially be one, one, and two. Is there an imbalance? Sure. There's an imbalance. Two is greater than one. I'm not debating that, but what we would say is the imbalance is not very large. Got it. Is that surprising to you though, that the annual, or I guess maybe the decompensation event rate was essentially, I guess maybe zero in your arm and placebo? Yes. We would say that we've always expected that the decompensation rate would not be linear. How we model phase III, we don't imagine that it's going to be an equal amount each year. We think that the numbers will grow over time. The reason we know that is that the five-year mortality for these patients is unfortunately about 50%. People don't get, they don't get diagnosed all at the same time, and over time, we think the events will accrue. Maybe one other question here on safety. Just the observation of bone mineral density loss. Walk us through what you did see between the 36 and the 96 weeks. I'd be curious to understand whether you measured, whether you measured it at the femoral neck at week 96 and what those findings were. Right. We measured BMD at baseline, and the FDA asked all FGF21s to look at that because it was a mouse data. The BMS pegbelfermin drug, which was discontinued, was asked to look at BMD as well, and I believe pegozafermin as well as the Boston compound. We looked at it at baseline and looked at it at week 48 and week 96. The difference from those two time points is from week, you asked about the change between week 48 to week 96, we saw roughly about a 2.5% decline, placebo adjusted, in both the lumbar spine and femoral neck in between the first year and the second year. You know, when we think about it, unfortunately, the patients in our study, they had multiple medical problems. Roughly 40% of the patients were osteopenic at baseline. Yet even though they were osteopenic, some of them on the verge of osteoporosis, only 3% of the patients in the active arm were receiving treatment for that. These are drugs that frankly were approved in the previous century and are generic, and it can be given as a once yearly injectable. What it really says is that we did not push our physicians hard enough, who are mostly liver doctors, to take care of an area that they do not have a lot of insight into, which is the endocrine metabolism of bone. When we go forward in phase III, we will be highlighting these issues and to emphasize to them too, these are their patients, the whole patients, and refer them out. Do you expect that the 40% osteopenic rate that you just mentioned, is that reflective of the broader population, or is that more just what you saw in the specific trial? Yeah. I think it's clearly what we saw in this trial, but at the same time, I think when one thinks of NASH, MASH in general, especially with cirrhotics, it's a more advanced disease. As a reminder, in the baseline characteristics, the baseline patient in our study, the average patient, was roughly a 66-year-old postmenopausal woman. The study was roughly 70% women, and most of them, given the age range, were postmenopausal. The bone mineral density profile for these patients is worse in general, as we saw from the baseline, than most average patients. I think when we go forward, we just acknowledge that patients with NASH, MASH, they do have complicated medical histories. Are you surprised that we haven't seen the same profile emerge for some of your other FGF21 agents? Yeah. So what we'd say is that for some of the other FGF21 agents, no one else has run a Cirrhotic study, so they don't know because they haven't conducted the study. The data for which there are available is in the pre-cirrhotic patient. Pegozafermin has run a 48-week BMD, of which they saw no difference in placebo versus their compound after 48 weeks. Similarly, when we ran our pre-cirrhotic population, like the pegozafermin, where it's been studied, we saw no difference between active and placebo at 48 weeks either. It is really with longer-term dosing, the two-year point in the pre-cirrhotic population, plus the cirrhotic population where we've seen this difference. Got it. Okay. So maybe too early to tell with some of these other agents. I think, yeah. Okay. Let's move to your phase III here. If you can just provide an update on where you stand with these trials and remind us of the expected timelines. Perfect. Our phase III program is just that. It is a program. There are three studies that comprise it, the first of which is what we call SYNCHRONY. All the studies are in the SYNCHRONY program. It is not very creative. The first one is called SYNCHRONY Real-World. These are patients who are non-invasively followed. They all have confirmed NASH, MASH, phase F1 through four, and they are being randomized two to one to being treated with efruxifermin 50 mg or placebo, and they are being followed for one year. There is not a second biopsy. This is designed to mimic what happens in the clinic. No one releases a biopsy for non-study patients. We are following them primarily for safety and tolerability, but we will also have VCTE, ELF score that we will be following on the efficacy side. We enrolled that study a little ahead of schedule, and we announced that in January of this year. It was a 52-week study. We expect to have results in the first half of 2026. Also, the second study is called what we call SYNCHRONY Histology. Those are F2, F3 patients who are randomized to either 28, 50, or placebo, and we're following them for 52 weeks. The primary endpoint is one-stage improvement fibrosis and MASH resolution as a composite. The study is still ongoing in terms of its enrollment, and we expect results in the first half of 2027. Lastly, the third study is what we call SYNCHRONY Outcomes. SYNCHRONY Outcomes being an F4 study, which we talked about a little bit earlier. We just enrolled the first patient in September of 2024, and we haven't quite given guidance yet, but we expect to later in the year. How are you thinking about the selection of the composite endpoint in the Histology study? Yeah. In the United States, the FDA allows as a primary endpoint either one-stage improvement of fibrosis without worsening of MASH or MASH resolution without worsening of fibrosis. However, in Europe, the EMA requires the and, so you need to have both. In that way, we just chose the composite endpoint, recognizing that it is an and and recognizing that the building blocks are the two separate components. The FDA will have what they need to have, and the FDA is aware of our primary endpoint. What are the implications of having that composite as you think about the study design and the powering? Yeah. So great point. We know from our two-year HARMONY data that the composite endpoint, because it's an and, allowed for a very small placebo response rate because you have to achieve both. While at the same time, there's roughly about a 5x difference when it comes to those patients, roughly 35% versus 7% who achieve that endpoint. For powering, having a small placebo is very helpful for us. That helped with the powering of the overall profile. Great. If you think about the phase III study in F4, one of the big debates here is on this selection of the endpoint and how the regulatory agencies may accept a biopsy endpoint. What is your latest understanding of the path forward here? I think when one thinks about that, one has to think about what the guidance in 2019 says, which is that the first sentence of the guidance says, "Since no study has ever demonstrated that there's an improvement in one-stage improvement fibrosis, we have to conclude that the best way is to look at outcomes." Given the data we've already talked about from our SYNCHRONY study, I think that sentence might need to be revised. In terms of how we're dealing with the agency, we're very comfortable given the language we received from the Europeans that they accept one-stage improvement of fibrosis in cirrhotics, and we're working with the division to get there. I know some other companies in the space are very clear that they have a pathway, and we feel that if they have one, we're likely to have one too. Great. Makes sense. Anything you can share? You know, we've touched a little bit on powering and how the choice of that endpoint has improved the powering of the study for your Histology study, but what can you share as it relates to your Cirrhotic study? Yeah. I think the Cirrhotic study has two components: cohort one, which is powered for biopsy, and the second component, which is really the outcomes. I think when one thinks about the biopsy, which is a little bit easier to understand, we were initially powered for, based on the 36-week results, but in light of the frankly unexpected and yet gratifying results that we saw in January when we had the 96-week data, we're re-examining the powering because the effect size was greater and the number of patients we may need in that cohort may decrease somewhat. We haven't reached a conclusion on how we're going to modify that. Given the nature of this cohort one is still enrolling, we still have a lot of runway, and we'll probably discuss that with the agency. We're not quite there yet. For your phase II-B, I guess maybe for that, for that study there, is there the potential that the 96-week data could support approval, or do you really need this phase III study? I think we really need the phase III study. As a reminder, as good as the results are, there really were 46 patients at the 96-week time point on 50 mg, and we believe there are roughly 1.5 million to two million Americans with NASH cirrhosis. Hard to see how that's going to translate in light of such a big population. Understood. That's a nice segue to where you see the commercial market evolving beyond just Rezdiffra, Rezdiffra, potentially sema getting their label expansion. You could be on the market as the second liver-directed agent for NASH. How do you see the commercial market? We see, as nicely developed by Rezdiffra and the Madrigal team, we see the market is quite large and quite a bit of demand for a drug that can improve and reverse fibrosis. We are excited for the F2, F3 space, and we are excited for the F4 space. Where do you see efruxifermin fitting in? We think given the chronology of approvals and the idea that, A, Rezdiffra has been, well, by the time we get approved, will have been on the market for several years. The fact that when the semaglutide product gets approved later this year, and remember, it is a line extension, having obviously had a diabetes indication for more than 10 years, we are not going to be first line. Unfortunately, for most patients on these drugs, the effect size is not the largest. There will be some patients who unfortunately were not served by either of those two agents, and hopefully we can help them. Got it. So that's for the F2, F3. Right. Presumably for F4, that's where you would really find. Correct. For F4, since we likely are the only drug to have a one-stage improvement of fibrosis demonstrated to date, we would probably be the drug of choice for those patients since there really isn't anything else. If Madrigal's outcome study is successful and they show benefit, albeit not with a biopsy endpoint, does that change your calculus as you think about where efruxifermin could be used in the F4 patient population? Not really, because I think it's a little bit like one-stage improvement of fibrosis in pre-cirrhotics. It works, and I expect that Madrigal's drug is doing so well. At the same time, as we move forward, drugs may come along that have a larger effect size. Even if they're approved and are successful in their outcome study, drugs that, as long as we are able to have a bigger effect size, may have the chance to benefit patients. As you think about how FGF21s will fit into this market space, there may be three of you coming onto the market in pretty short order. How do you think about the relative split between efruxifermin, pegozafermin, efimosfermin alfa? Yeah. Is there enough differentiation? I think it's incumbent on us as the company and 89bio and now GSK to create that differentiation between us so that physicians and patients have enough data from which to choose. We're happy that when I think about it, that there are multiple choices because that's how they are. We think about diabetes, think about statins, think about PD1s. There are multiple choices within the space. I think the net of this is all benefits physicians and patients. What has your market research suggested to you on that point about which FGF21 will be the agent of choice? Of course, our market research is we have some ideas and concepts that may not be borne out, but I would say that given the data that we do have and we're the only compound with data, it obviously looks on our data a little more fair. We await the results from the other two companies, and we'll have a better answer for you once we see those results. All else equal on efficacy and safety, how important is the dosing, the dosing frequency? I think the dosing frequency, obviously less frequent dosing is better, assuming that there's no difference in the safety profile. I think in some cases, there are in other classes, there are drugs that may be administered, let's say, monthly versus weekly, but it's multiple injections given on the same day, which may not distinguish themselves favorably compared to other drugs. I think it all depends. If it's one injection once a month with the same volume, I think that is very favorable. I'm not sure that that's the situation we currently have in the FGF21 space. Got it. What is your understanding right now of how payers might approach an FGF21 being on the market, particularly as it comes behind some other agents that will be potentially cheaper, more entrenched in the marketplace? I think it's one where it's incumbent for drugs that always come later to demonstrate value. Especially if they want to charge a premium to it, then they really have to make the case that they deserve that payment. That has to be demonstrated clinically. They have to prove, I mean, of course, you can do that in a head-to-head study, but in the absence of that, you really have to make a very clear case that your drug merits that differentiation. That's incumbent on us to win that battle. If you're able to make that argument that there is differentiation, do you think payers would forgo any type of step-through requirements, or is that still probably on the table? You know, payers have a lot of tools to advantage or disadvantage your product, some of it based on the clinical profile, but some of it based on the economics. How you're able to negotiate or navigate that pathway, I think, is a little bit of a TBD because the TPP Target Product Profile still is established in phase III. We do not know what that will be. We also cannot understand exactly how the market will be as we move forward. A lot of it will have to do with price and has to do with rebates. There are a number of things that can influence whether how step edits are used and how products are advantaged or disadvantaged. What are your thoughts on combination use? I think combination use is here to stay. It already is here. Recall that even in our SYNCHRONY study, 20% of the patients were receiving GLP-1. Combination use is there. Was it combination use for MASH? Was it combination use for diabetes? Combination use for any other indications, obesity that were being used? I think when one thinks about a drug like a GLP-1 that has multiple indications, it is likely to play a role given the patient population and likely to be here for quite some time. Mechanistically, do you see rationale for combining efruxifermin with another liver-directed agent? We don't have a lot of data, so we don't have any data with something like Madrigal's compound because it was just approved last year. Most of the data we have today preceded that. I think one can see drugs that can work for patients, and I think there's a lot of flexibility. We're not precluding any one of those things, but I think until the data are available, it's a little tougher to assess accurately. For all liver-directed drugs or some, we'll have to parse that more carefully. Maybe just on that point, as you are enrolling your phase III study, Rezdiffra on the market now, how are you handling those patients who may have been exposed to the drug? I think right now for phase III, we're allowing those patients because it's an approved agent, but it's one of those things that we stratify by. Got it. Okay. Interesting. Maybe in the final couple of minutes that we have here, given the FGF21 mechanism, are you interested or do you see utility in exploring other adjacent indications outside of NASH? We do. I mean, I think that's one of the questions we often get asked by investors is, what are you going to do about your pipeline? When we think about that, most commonly that's done for many companies is, oh, let's look at a novel new molecular agent. What would be that entity that we'd be studying? That is a pathway we could change. There are some things that are interesting to us. At the same time, given the result we have in F4 that we can reverse cirrhosis, that's particularly interesting to us because cirrhosis has been challenging for decades, that it's been irreversible and really been a very challenging position for patients and physicians. As we look at how to address that, we think we have a valuable sort of beachhead, as it were, in we've demonstrated cirrhosis, which is a common response of the liver to a variety of insults. In our case, it's due to NASH, MASH, but there are other insults that result in cirrhosis. It may be a better use of our resources and of the agent to capitalize on the investments we've made in terms of manufacturing, toxicology, CAR- T studies, all the preclinical work that's gone in, and perhaps explore other causes of cirrhosis as something we may want to follow up on. Interesting. Any interest in, I guess, because you do have such a potent antifibrotic agent, any interest expanding even beyond cardiometabolic into maybe like pulmonary fibrosis indications? We feel the fibrotic pathway is pretty common. The balance between degradation and synthesis of new collagen is applicable for a lot of different organs. I would say that to do that, let's say in the pulmonary, let's say we were to look at other fibrotic diseases of the lung, that's a little bit of our farther putt, as they say. We probably need to do a phase II- B study to really have proof of principle. At the same time, within the liver, I think we're less likely to do that. We potentially could go straight into phase III. Of course, that requires consultation with the agency. I think staying within the liver is a little bit easier, a little more less of a stretch, but it doesn't preclude us from going outside the liver. Got it. Maybe the final question here, just remind us of your cash runway. Where does that get you to? Yeah. So we're fortunate to have investor support that we have $1,128 million in our last report of our Q1 earnings. That gets us into 2028. Got it. Into commercialization? You know, we haven't given that, we haven't been as granular as how that gets us into 2028. Okay. With that, thank you, Andrew, so much. Thanks again for having me. Thank you, everyone.