Akero Therapeutics, Inc. (AKRO) Earnings Call Transcript & Summary

Okay, great. Good morning. Welcome. I'm Eric Joseph, senior biotech analyst with JPMorgan. And our next presenting company is Akero. Presenting on behalf of the company is CEO, Andrew Cheng. There will be a Q&A session after the presentation. [Operator Instructions] So with that, Andrew, thanks for joining us.

Good morning. Thank you, Eric, for having us. So 2025 is going to be a very exciting year for Akero, and I'd like to begin by talking a little bit about the year ahead of us. So let's move on to the first slide. This is our safe harbor statement, which is in very small 8-point font, and I will not read, but I'm going to pause so that I can be compliant with the safe harbor and legal disclaimers. Okay. Let's move to the next slide. So when you think about the things that have taken place over the last year or so for Akero is that we've really made the transition from a Phase IIb company, which we had both primary endpoint results for our Phase IIb F2-F3 pre-cirrhotic study in 2022. And then in 2023, we had our primary endpoint for our Phase IIb cirrhotic study. Those have progressed in that we had the 96-week readouts last March for the pre-cirrhotic study and upcoming next month, we'll have the 96 readout for the Phase IIb cirrhotic study, which we call SYMMETRY. In that time frame, we've also started our Phase III program, which was initiated with the 2 studies, which we are calling SYNCHRONY as part of a 3-study package. The first 2 studies, SYNCHRONY Histology and Real-World began in the Q4 '23, and yesterday, we very excitingly announced that we completed enrollment in the first of our Phase III programs. That is SYNCHRONY Histology, which is a -- excuse me, SYNCHRONY Real-World which is a noninvasive study, looking at patients who are F1 through F4 in a randomized, double-blind, placebo-controlled fashion 600 patients over 52 weeks, and these patients are followed noninvasively. So this is -- the primary goal of this trial is 1 of safety and efficacy, but it is 1 which the patients, although they did have a biopsy to come into the study patients came from screening from SYNCHRONY Histology, there will be -- there's not a second biopsy. They all be followed it for noninvasive manners looking at both efficacy and safety. And we -- importantly, because the study was fully enrolled we announced yesterday, we'll read out in the first half of 2026. And as we've done in previous studies, as the time drops closer, we will refine that time point because you can imagine that with the first point, yesterday at 1 year later is -- will be quite -- we can narrow that window. Well, why don't we move on just by way of background just to understand what efruxifermin is. Efruxifermin is a bivalent FGF21 analog that is an Fc fusion protein that we -- the founders, Tim Rolph and Jonathan Young, enlicensed from Amgen in 2017. And and that really is the basis for Akero. Importantly, FGF21, as you may recall, native FGF21 has a very, very short half life that doesn't make it suitable to be a drug, and what the Fc fusion protein does is, it extended the half-life to between 3 to 4 days. And it also has modified in the FGF21 portion, mostly at the C-terminus, you can see modifications at the 171 and the 180 residue. And you can see that it's important that it enhances the binding to the co-receptor beta-klotho as the cartoon designates the interaction of EFX in order to transmit a signal is a trimeric interaction. The C terminus is FGF21 binds with the co-receptor beta-klotho anchoring to the cell surface. And then the end terminus is able to bind the FGF receptors, whether it's 1C, 2C or 3C to transmit the signal through the trans memory domain as diagrammed in the cartoon there. Importantly, that what we've seen through our clinical trials is I mentioned that we've seen sustained pharmacodynamic effect through 2 years in our FGF3 portion through 36 weekend with our F4 patients, which will follow-up on soon in the 96-week readout. Why don't I turn now and talk a little bit about the cirrhotic patients because that's what's -- we're reading out next month. And just as a reminder, we borrowed this slide from an FDA presentation. It's from patients in gastroenterology, but the FDA has used so we thought we would use it as well. It just highlights the importance and unfortunately, the acute medical need for patients who are cirrhotic. In red is a Kaplan-Meier curve. And you can see that the 50% mortality for patients who are diagnosed is F4 outside of liver transplantation is unfortunately 50% mortality is at 5 years, and is dramatically different when you look at the other pre-cirrhotic stages, if 1 were to go to the right on the Kaplan-Meier curve, you can see that the, let's say, the F2 or F3 patients, that same 50% mortality occurs at about 15 years. So really, there's a pretty stark difference in terms of the outlook for patients who are pre-cirrhotic versus cirrhotic. And that really highlights the need to have therapeutics for this population for which, unfortunately, there is no approved agent this population. Turning now to the SYMMETRY study, which is our Phase II trial. As a reminder, it's a randomized double-blind placebo-controlled study looking at 2 doses of efruxifermin, 28 or 50 milligrams versus placebo in patients who are compensated cirrhotics that is their F4 Child-Pugh A patients. So the key inclusion criteria really is listed here that they're biopsy-confirmed, type 4, Stage IV MASH, and compensated cirrhotics with either type 2 diabetes or 2 of the formal components of the metabolic syndrome. The primary endpoint readout at week 36, and I'll talk about that momentarily. And as a reminder, we're now in February reading out the 2-year data that is week 96. Keeping in mind that we're not powered for this endpoint. The primary endpoint was at week 36. There are key secondary end points. I won't read through all of them, but they're listed there that we revealed also at week 36, but will also be looked at week 96. So turning to the next slide really talks about the -- on the bar chart on the left, we can see that these are the week 36 results at the primary endpoint. That is for patients who had a 1-stage improvement of fibrosis without worsening of MASH, it demonstrated that the 50-milligram arm demonstrated a 24% one-stage approved in fibrosis, in contrast to 22% for the 28-milligram dose and placebo at 14%. As noted in the bars that neither the 2 EFX arms reached significance when compared with placebo. But as you'll see in a follow-on slide, these are among the best results ever seen in this population. We also conducted a sub-analysis on the bar chart on the right. The subgroup looks at patients who had -- were either diagnosed for greater than 6 months prior to study entry as having cirrhosis or cryptogenic cirrhosis. That is those patients with the most advanced form of Child-Pugh A those who have sometimes is referred to as burned out MASH, that is that they have relatively little liver fat because much of their liver has been replaced by -- and the hepatocytes be replaced by fibrosis. And in that population, we see that roughly the efficacy is largely the same, 22% for the 50-milligram dose. But interestingly, the efficacy drops for the 28-milligram dose and interestingly, for placebo, down to 3%. So it's something as when we looked at a relatively large subgroup, more than approximately 60% of the patients in the readout, we see some differences when it comes to the response rates in the placebo and the 20-milligram arm overall, looking at that primary endpoint. I mentioned earlier, looking at it, this is 1 of our landscape slides, and I'll just call your attention to, this is a placebo-corrected slide. So when it looks at the other compounds that have been studied for F4 NASH, you can see a variety of different companies. Two of the studies come to my former company, but also different mechanisms, some FGF21 as well as LOXL-2 GLP-1 from semaglutide from Novo. And there is 1 unfortunate similarity putting all the studies to the right is that really the results were largely very placebo-like. And in some cases, placebo had a better response than some of the patients treated with active. If you look at the semaglutide results or the Bristol-Myers pegbelfermin results, placebo exceeded the active arm, and you can see that's represented by the negative number. So clearly, this has been a difficult field and to have successful trial results. And I mentioned earlier that you see the Akero efruxifermin results, although not statistically significant, as I pointed out earlier, were the best results seen in the field to date, at about 8% and 10% placebo rejected effect sizes But 1 of the challenges when 1 looks at biopsy overall is that the liver is among the largest solid organs in the body, yet we're looking at a biopsy of using a 16-gauge needle, and you're looking at 10 or 11 portal tracks. And it's quite small. How does this local 1 looks at the entire liver looking non-invasively? And you can see that at this study, you can see that when 1 looks at some of the more reliable noninvasive measures was the ELF score, a composite score, liver stiffness or Pro-C3, you see important improvements in both the ELF score, statistically significant versus placebo and in Pro-C3 as a marker of inhibition of new collagen synthesis, patients treated with EFX at either dose have responded very well. And you see this is consistent with what we've seen in prior pre-cirrhotic studies. This is an example of 1 of the patients, and I think this is something that we did not fully expect to see. That is that this is a patient histologically that had a 3-stage improvement of fibrosis. They came into the study, and you can see the baseline biopsy on the left, which is F4, you can see the extensive bridging fibrosis as well as a nodule on that slide. And after 36 weeks of treatment and a mild weight loss of about 2 kilograms, they -- this patient was this 69-year-old woman, managed to be F1 after 9 months of treatment. So this was a remarkable improvement. We have 2 patients in each of the arms or 1 patient each arm, 2 patients total have 2-stage improvement of fibrosis as well as a 3-stage improvement of fibrosis. So really, when we look at this, we see the potential for EFX to reverse fibrosis in patients who are cirrhotic, something which some physicians had and investors had a question, was at all possible, but the histologic evidence is here on this slide. At the same time, looking at noninvasive measures, so this is a NASH score on the right-hand side, 1 looks at histology, fibrosis markers. We'll focus on the NASH Score at the top, you can see at baseline, the patient at a NASH score of 5 with 1, 2, 2 across the categories. And after 9 months, the NASH score was 0. So really both both measures looking at liver biopsy for fibrosis NASH score and looking below when we look at noninvasive markers, see improvements in ELF Pro-C3 as well as FAST. So again, a very consistent picture for this patient, both histologically and as well as noninvasively. So when 1 thinks about this, 1 of the questions I often get asked is, well, that's great. that this patient has done well at 36 weeks. How will this read out at the 2-year point at 96 weeks, we'll read out week, why do you think things will improve. And to that, we look at some of the results from previously I mentioned in the HARMONY study. So as a reminder, similar trial design, different color scheme, but we have 2 doses in a randomized double-blind placebo-controlled trial of F2-F3 patients. All the patients were biopsy confirmed Again, the primary endpoint is slightly early at 24 weeks. But then at 2 years, we had a follow-on biopsy. And importantly, what we see is that when 1 looks at 1 stage improvement of fibrosis, which is on this slide, these are the results sort of shadowed in -- for both doses. You see statistically significant results at both -- for both doses at week 24 versus placebo, roughly 40% versus 20% but interestingly, when one looks at what happens at 96 weeks, we see a real expansion, especially at the 50-milligram arm of the response rate going from 41% to 75%. And then really when one looks at this, it really tells us that longer dosing has improved the response. And the question was, what is the color around that longer dosing? Are these the same patients, different patients? Or when one looks up -- let's see if I did that wrong. So here we go. Going to the next slide is that we've broken this down in the -- within the bar charts of the 75%. I think it's the easiest to look at there. And you can see that, we have a group of patients who had a sustained response, 11 out of the 21 patients who -- of the 75%, and those patients had the -- had a response at week 24, but also maintain the response out to week 96. But interestingly, the -- roughly half the patients, 10 out of the 21 were new patients, people who were not successful at week 24, but then with increased dosing became successful at week 96. So we're encouraged that the anti-fibrotic effects and the benefits of this compound are not -- they don't plateau at the 6-month period. They can be maintained and extended, so that's 1 of the strongest points for us that we think that longer dosing does matter for this compound, and it can be manifested in histology. And so when we break this down and look at the subgroups, I think to give a little -- put some numbers around it, the top box really looks at patients who had the sustained response, and you can see for the 50-milligram dose, that number is 92%. 11 out of the 12 patients who were successful at week 24 maintained and were continue to be successful. So we have a durable response for those patients. And then for the people who were nonresponders at week 24, you could see 63% of those who of the 10 out of the 16 became responders. So we continue to bring in new successes. So longer dosing does benefit patients regardless where they were successes at week 24 or not. Now 1 of the other questions is when one looks at the slide, you can see that we've expanded the breadth the patients who are responders. But what happens to patients who are already responders? And can the depth of response increase? And this is a measure of 2-stage improvement of fibrosis. And in this slide, you basically see that very point is that in the -- using the same schema, you see roughly 15% of the EFX-treated arms had a 2-stage improvement in fibrosis at week 36 -- excuse me, at week 24. But by week 96, you can see that's increased to 36% in the 50-milligram arm and 31% in the 28-milligram dose. So again, now longer dosing has done both things. It's both expanded the breadth of response but also increase the depth of response. So one thinks of a 36% 2-stage approval of fibrosis, that is a number, quite honestly, is quite strong. And that's -- as you've seen on the slide, highly statistically significant when compared with placebo. Let's turn now to the patients who have F3 fibrosis. One of the reasons we bring this up is investors often ask a lot of these responses driven by the easier-to-treat patients who are F2. There's less fibrosis, maybe all of the patients who have a 2-stage improvement are driven by the F2 patients. We've just narrowed the analysis to focus on the F3 patients, the hardest-to-treat pre-cirrhotic patients. You can see the response rates at week 24, 29% and 28% on the treated arm versus placebo. And when one expands out to week 96, you can see that roughly 68% of the F3 patients have responded. Yes, smaller than the average of 75%. But again, very robust response and when one thinks of more than 2/3 of patients by 2 years who are F3 baseline having a response of 1 stage improvement in fibrosis. And you can see that's in contrast to 14% on placebo. So again, that response is highly statistically significant. And when 1 looks at this, you can see that breaking this down into the similar slide of the patients who are F3 who had 1 stage or more of fibrosis. You can see on the 50-milligram dose, actually, the majority of those patients, 8 out of the 13 had a 2-stage improvement in fibrosis, even though there -- so the harder-to-treat population, yet they still were able to have a 2-stage improvement of fibrosis with extended treatment. So when one thinks about the totality of the data, it's this response rate, which is 75% 1 stage improvement of fibrosis is not driven exclusively by the F2 patients. It's shared almost equally between F2 and F3 when 1 looks at the pre-cirrhotic patients. One of the questions that's come up from -- mostly from physicians or our investigators is that we all recognize how important biopsy is as it's the FDA and EMA regulatory standard for approval. But at the same time, clinically, biopsies are not used as often. So what the pushback and the question for us is, when you think about this compound being approved, how will noninvasive measures be able to guide us because that's what -- patients aren't eager to have biopsies. It probably comes as no surprise. But how can we follow these patients and what noninvasive measures are helpful. So these are data set, and I'll walk you through. It's a little bit complicated that we presented at last fall's AASLD meeting, the Society of liver disease in San Diego. What we've done is taken the patients who have had 1 stage improvement of fibrosis, and that's 1 of the circles, and then we've wanted to see how much overlap with their -- is there with common noninvasive measures. The noninvasive measures we've used or liver stiffness, which is generated from a fiber scan. And it's a liver stiffness response of greater than equal to 30%, which is often correlated with clinical benefit, and an ELF score of reduction of greater than equal 0.5. And what you can see is that on the far left in placebo, of the patients start to roughly half the patients, 47% of the placebo patients had none of those attributes, not a single one. And then when you think about those that had overlap, as you could see with the overlapping Venn diagram, you can see that the placebo response, none of them had more than one. So even for the patients who had, had a one-stage fibrosis, they had neither liver stiffness improvement or ELF. And what that really shows is that the placebo response is likely a representative of a sampling error, the liver being heterogeneous, and that there are times when 1 part of the liver may be F2 or F3 or F1. And when you see it improve it, it's not really correlated with the noninvasive measure, which is a representative of the whole liver. Now in contrast what you see, let's just move to the far right in the 50-milligram dose is that when 1 looks at the patients who had no -- none of those measures, meaning that in contrast to the placebo 47%, that didn't occur. Every single 50-milligram patients had at least 1 of those measures, whether it's fibrosis improvement on histology or either the ELF score improvement greater than the 5% or the FibroScan improvement. So that's -- it's not so common that things are black and white in clinical studies, but this is 1 of the most important, and then when 1 looks at the patients that had all 3 events, roughly 40% of the patients had that event. So improvement of fibrosis, correlated and overlap with both noninvasive measures. And you can see the 28-milligram is in between. So we have a nice dose response. But what this data helps highlight is that for EFX, the histology does correlate well with a whole body -- on whole liver, excuse me, noninvasive measures. And it's an important guide when it looks forward to when this compound is approved, how physicians use this. You could see that they could use either or both of these noninvasive measures to follow their patients. Let me turn now to the next slide. Turning to safety. This is, again, important. Importantly, nobody died in the study to date. There were serious adverse events that we're seeing anywhere from 9% to 16% depending on the groups. The number of patients that had a drug-related serious adverse events was 1 in each of the EFX arms. So just a small number of patients, the reasons are listed on the slide. The most common adverse events were GI in nature, diarrhea and nausea, but keeping on relatively few patients discontinued for either of those 2 events despite the number being roughly about 35% to 40% for each of those adverse events. So overall, the drug has been relatively well tolerated. You can see that the discontinuation rate is less than 10% after 2 years, 1 thinks about these events. And that's an important thing on 1 interprets this slide to look at the duration of study because it's cumulative. Other safety measures to look at, blood pressure, there's no statistical difference in either systolic or diastolic blood pressure 2 years when compared to placebo. There are markers of hematologic function in hemostasis, whether it's platelets, bilirubin or the composite scores of MELD and Child-Pugh, they remain stable, progression of cirrhosis with balance across the group is relatively small, fewer than 5 patients in each arm and roughly similar between the groups. There were no significant changes in bone mineral density at 1 year with the EFX arms compared to placebo. We did see a 2 years significant reductions of between 3% and 4% at the lumber spine and reductions at the 50-milligram dose only, not at the less than 3% of the femoral neck. It's important to keep in mind that some of the differences were driven were aided by an increase of about 8.8%, 1% in the placebo arm. In terms of fractures, the fractures were relatively similar between the groups. The worrying fracture of vertebral fracture was only seen in the placebo arm at the first lumber era. So lastly, I'll just conclude. As we think about the SYNCHRONY Phase III programs, which we're in the midst of. On the far right, it's a SYNCHRONY Real-World noninvasive study. As I mentioned earlier in the presentation, we've completed the double-blind enrollment. And we're very excited about that with the first readout in the first half of next year. And for the SYNCHRONY Histology, the registrational biopsy study that enrollment is ongoing still, but we expect the readout to be in the first half of 2027. So we're very pleased with how that's going. As a reminder, that study is also powered for end points at 5 years at 240 weeks, the primary endpoint outcome. So we'll be following not just for the 1-year histology readout that will lead -- that will lead to a filing for accelerated approval but will be followed for long term outcomes. Lastly, the third study is a SYNCHRONY outcome study, which is an F4 compensated cirrhotics, that is randomized double-blind placebo-controlled study looking at 2 doses -- 1 dose, not 2 of EFX, just the 50-milligram dose. The primary endpoint for biopsy will be at 2 years like the data we'll soon see, and that is the outcomes portion of it, the clinical events that we're looking at the hepatic clinical events will be followed for approximately 260 weeks, roughly 5 years. And there are key secondary endpoints that are listed here. But with that, I'll probably stop and thank you for your attention.

Okay. Great. We have time for some questions. [Operator Instructions]. But actually, we have a question submitted me the portal. So I think I might start there. And this is sort of a mechanical question related to the mechanics of the 96-week readout coming with the SYMMETRY trial. Do pathologists reread baseline biopsies, right? Both baseline and 36-week biopsies as part of the 6-week assessment. Is there any potential for sequence bias? And do you use the same 2 to 3 pathologists in scoring histologic change?

Okay. So that's a multilayer question. Let me just go back towards the ones I can remember you will remind me on the portion I forget. So the number of pathologists is the same. So there are 3 pathologists. We follow the same practice that we have in the HARMONY study that is that 2 pathologists have to come to consensus. And if they can't come to consensus the third will serve as an adjudicator. But there's really -- the study is mostly read by 2 pathologists, and the second question or maybe the first part of the question was, I believe, about sequence bias. So we address sequence bias by inserting randoms slides that sort of are screening biopsies that are done throughout -- so they're -- as they're reading the reread some original screening samples that may not be patients who are actively in the study, but they can't assume that because the patient is later in the trial that's necessarily a 96-week biopsy. They don't, however, reread the baseline at 36 weeks as part of the [indiscernible] they're not part of -- we're not rereading those. There are just some samples that are used to address the sequencing issue, but without reassessing the biopsies that have already been read out.

Okay.

I think that's what the question was.

Yes. That seems to be true to you pretty well. Maybe in just the second part of the question is -- and I'm sure you get this a lot, we certainly do, which is just how to think about the retention -- patient retention at the 96-week readout given that it's likely that these are sicker patients relative to the -- those in the the non-cirrhotic patients assessed in the HARMONY trial.

Yes. So I think that's very important. We get that question too. So the patients are sicker. These cirrhotic patients have more advanced liver disease, but they have more advanced everything disease, diabetes, cardiovascular disease, they're just -- unfortunately, they face a lot more -- the greater number of medical challenges. That being said, the question is really focused on retention. So unlike the pre-cirrhotic patients for which they're thankfully is now 1 approved drug, there are no approved drugs for F4, so while they do face more advanced disease at the same time, they also -- because of the week 36 results, they know that this compound has led to 1/4 of patients on the 50-milligram arm being no longer cirrhotic. And that's a pretty compelling reason to stay on the study. There is another reason, which is that like the HARMONY study, the SYMMETRY patients who are randomized to placebo are offered open-label drug in Study 107 as a follow-up and just as a way to balance committing to a placebo in a clinical trial for 2 years, so it's both -- so it's a reason to stay on the study because there is the opportunity to access open-label drug.

A question here?

So quick one. Similar to trial, are the patients being followed by noninvasive methods like FibroScans or just the biopsies at the week 38 -- 36 and week 96?

They're being followed by both, biopsy week 26 -- 96, but the noninvasives, whether it's ELF-score, FibroScan are continued from week 36 onwards. So we will have all of those data at week 96.

so it will be a little bit an additional 6 weeks -- 60 weeks since the 36-week assessment. I guess how -- what is your expectation around the sort of the level of deterioration or fibrosis worsening on the placebo arm, maybe perhaps referencing the existing natural history or your clinical data. Is there sort of an expectation that you would have us keep in mind in terms of how the placebo arm may perform with the longer time plan.

Yes. So unfortunately, as I shared from the Kaplan-Meier curve, the pace of clinical dysfunction or demise is more rapid for F4 patients. So you saw that at the -- at 5 years, 50% of the patients will -- there's a 50% mortality. And so when one thinks of a placebo patient for 2 years being untreated. One would think the portion of the liver that is F4 would progress. So one thinks recognizing -- and this gets at the false positive sampling is that say that a patient at baseline is roughly half F4, half of 3, it's very unlikely that they would -- that ratio would remain the same and be so at 2 years. And so as a result, the increasing proportion of liver that is F4 more likely than not will lead to a likely lower placebo false-positive rate at week 96. Now we don't expect it to be 0, but we don't -- we'd be surprised if it's the same number or higher.

Just on the tolerability profile. In the F4 population, and specifically, just on the point of bone loss -- the potential for bone loss. -- may yes, can you just sort of talk about the -- any incremental propensity to experience bone loss in the F4 population relative to the non-cirrhotic population? And what would be an acceptable sort of loss margin for still chronic treatment of the cirrhotic population.

Yes. So in the cirrhotic population at week 36, we did see a nonsignificant difference at the lumber spine at week 36, and then we did see a significant difference in the hip. That contrast with the week 48 measure in the non-cirrhotic, which was both recent a placebo-like I think it really speaks to the advanced disease that these patients face, not only in diabetes, liver disease and as well as bone disease. I think in terms of what the benefit risk is, I think what you're driving at, Eric, I think the benefit risk is very different in the population primarily because of the mortality as being so acute. I'll ask also is the fact that unfortunately, a lot -- many of these patients had osteopenia at baseline, but were untreated with pretty basic measures of standard of care, which are calcium vitamin D supplementation as well as existing drugs anti resorptive drugs for osteopenia that were not being utilized. So as we go forward, we're highlighting the importance of bone safety for all patients in this study and that's something we hope to improve upon in Phase III.

You highlighted kind of almost a subpopulation to some extent within the cirrhotic population, those with cryptogenic cirrhosis, right, or that kind of burned out cirrhosis in SYMMETRY, ITT, it seems like that comprise about 17% of the population is how reflective is that of the sort of real-world prevalence of that subtype, and for your ongoing SYNCHRONY outcomes trial, how is -- I guess, what allowances are there for -- what's the expected composition of cryptogenic patients? Is there an enrollment cap or quota there?

Yes. So I think cryptogenic patients are among the most advanced compensated cirrhotic patients that there are. That's why they're -- they don't have as much fat because fibrosis is largely sort of moved that out from the hepatocytes, I think there's not great data on what the true in terms of natural history, what the percentage is, the numbers we've seen are up as many as 15% of the patients. So at 70%, we're a tad higher in terms of where the study is we've seen in terms of our entry criteria, likely be similar to what we had in SYMMETRY, probably around 20%. So will we get there? We're not sure. But I think it's important 1 thinks about an outcomes-based study the more advanced patients are those who reach outcomes sooner. So it's important, which is why we included them in Phase II -- Phase IIb is to help us understand how they respond and how they the drug and how suitable they would be to have in Phase III.

And just picking up on the progress update with SYNCHRONY Real-World, having fully accrued that trial, kind of a broader eligible patient population drawing across the non-cirrhotic and cirrhotic spectrum. Just to what extent does sort of the enrollment pace there inform the pace of enrollment of SYNCHRONY Histology. And I guess how is accrual there trend relative to expectations?

So I think it's important to note that everyone who has a SYNCHRONY Real-World patient was screened for SYNCHRONY Histology. So the fact that this trial enrolled as rapidly as it has is reflective of the screening pace in SYNCHRONY Histology, so I think when one looks at that, we're pleased with what's happened in the SYNCHRONY Real-World. Similarly, we're pleased with where we are with SYNCHRONY Histology.

All right. Well, I think we might leave it there for questions. So thanks, everyone, for tuning in to the session. And thanks for the presentation, Andrew.

Thanks very much for having us.