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

Good day, and welcome to the Akero Phase IIb HARMONY Week 96 Data Presentation. [Operator Instructions] As a reminder, this call is being recorded. I would now like to turn the call over to Bill White, CFO and Head of Corporate Development. You may begin.

Thank you, and good morning. Joining me today are Andrew Cheng, President and CEO of Akero; Kitty Yale, Chief Development Officer; and Tim Rolph, Chief Scientific Officer. Today, we will be sharing top line 96-week results from our HARMONY Phase IIb clinical study for efruxifermin, or EFX, for the treatment of pre-cirrhotic MASH. Before we begin, I ask that you please read the disclaimers presented on Slide 2. And I'd like to remind you that various statements that we may make during this call will include forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including expressed or implied statements regarding implications of this analysis of the HARMONY study, our future plans, including our plans around the development of EFX, prospects and strategy, financial goals and guidance, product attributes and pipeline, drivers of growth and other statements that are not historical facts. Such forward-looking statements are not guarantees of future performance, and therefore, you should not put undue reliance upon them. Management's assumptions, expectations and opinions reflected in these forward-looking statements are subject to risks and uncertainties that may cause actual results and/or performance to differ materially from any future results, performance or achievements discussed in or implied by such forward-looking statements, and the company can give no assurance they will prove to be correct and will not provide any further guidance or updates on our performance during the quarter unless we do so in a public forum. Please refer to the press release we issued today and risk factors included in the company's filings with the Securities and Exchange Commission for a discussion of important factors that may cause actual events or results to differ materially from those contained in our forward-looking statements. Prior to this call, we issued a press release regarding the top line results from our Phase IIb HARMONY study, which is available on our website at akerotx.com under Press Releases in the Investor Relations section. The presentation we'll walk through on today's call will be available immediately afterwards under Events and Presentations in the Investor Relations section of our website. I will now turn the call over to Andrew Cheng, Akero's President and CEO.

Thank you, Bill, and thanks to all who joined today's webcast. I'm excited to introduce today's results from the Phase IIb HARMONY study following treatment with EFX for 96 weeks beginning on Slide 3. As you may recall, we shared the results of HARMONY's 24-week primary endpoint in September of 2022, for which the study was fully powered for statistical significance. We did not design the HARMONY study to be fully powered for the week 96 endpoints we are discussing today. Nevertheless, as we reported this morning in our press release, the 50-milligram EFX dose group achieved statically significant differences relative to placebo on fibrosis improvement of at least 1 stage and no worsening of MASH; fibrosis improvement of 2 stages and no worsening in MASH; MASH resolution and no worsening of fibrosis; and finally, a combination of fibrosis improvement and MASH resolution. The 28-milligram EFX group achieved statistically significant differences for every histology endpoint, except 1 stage improvement of fibrosis without worsening of MASH. These statistically significant results are even more compelling when one considers that the placebo rate on the endpoint of fibrosis improvement without worsening of MASH increased between week 24 and week 96. The study sample size and increased placebo rate suggest that the statistical significance reported today reflects the magnitude of EFX's unprecedented effect sizes observed across multiple histologic endpoints. I'd now like to turn the presentation over to our Chief Development Officer, Kitty Yale, to walk through the compelling results in detail.

Thank you, Andrew, and good morning, everybody. I'd like to begin with a reminder of the design of the HARMONY study, which is shown on Slide 4. The HARMONY study was a Phase IIb randomized, double-blinded, placebo-controlled, multicenter, dose-ranging trial in adult patients with biopsy-confirmed MASH with fibrosis stage 2 or 3. Patients were randomized to receive once-weekly subcutaneous dosage of either 28 or 50 milligrams of EFX or placebo for 96 weeks. As Andy mentioned, the primary endpoint at week 24 was reported in September 2022 and was the proportion of patients with F2, F3 fibrosis to achieve at least the 1-stage improvement in fibrosis without worsening of MASH. The primary endpoint at 24 weeks was the basis of the primary assumptions and the sample size of HARMONY. Today, we're reporting the end-of-study preliminary top line analysis after 96 weeks of treatment with EFX. And these include the key histology endpoints of the proportion of subject to experience at least a 1- or 2-stage improvement in fibrosis without worsening of MASH, the proportion of subjects to experience MASH resolution without worsening of fibrosis as well as the proportion of subjects to experience at least a 1-stage improvement in fibrosis and MASH resolution. We are also reporting a change after 96 weeks relative to baseline and placebo for noninvasive markers of liver injury, fibrosis, markers of overall metabolic health as well as safety and tolerability. Group sizes and analysis set are defined on Slide 5. The full analysis set comprised of all 128 patients who were randomized. The safety and the modified full analysis set, which we refer to as the intent-to-treat, or ITT, includes all 126 patients that were randomized and received at least 1 dose of study drug. The liver biopsy analysis set used for the week 24 primary endpoint includes 113 patients with baseline and week 24 results. The liver biopsy analysis set at week 96 includes 88 patients with baseline and end-of-treatment biopsy results. There were 34, 26 and 28 patients for the placebo, 28- and 50-milligram dose groups, respectively. On Slide 6, we review the baseline demographics, which have been shared previously. As a reminder, these are generally comparable to those observed in biopsy-confirmed MASH patient population. However, patients in HARMONY exhibited characteristics of more advanced-stage disease. Approximately 70% of the patients had type 2 diabetes and 2/3 with Stage 3 fibrosis. Only 13% in HARMONY were on a stable GLP-1, and therefore, subset analyses of the study are not meaningful. I would, however, point you to our Phase IIb SYMMETRY cohort B study, which demonstrated that the safety of the combination therapy given together were similar to those given alone and also the add-in EFX to a GLP-1 therapy significantly improved noninvasive markers of MASH-related disease. Before diving into the histology results, let me point out that the biopsy analysis methodology [indiscernible] was unchanged between weeks 24 and 96. So turning to our efficacy data on Slide 7. We report the results for those patients who completed the week 96 endpoint of fibrosis improvement of 1 or more stages without worsening of MASH. For the 50-milligram EFX group, fibrosis improvement was achieved by 75% of patients, which was statistically significant compared to that for placebo at 24%. The response rate for fibrosis improvement without worsening of MASH trended higher for the 28-milli group -- 28-milligram dose group at 46%. The improvement of the 50-milligram EFX represents a 34% deepening of response from the previously reported week 24 analysis, that is, from 41% to 75%. [ And fortunately ], the response rate for the 50-milligram EFX group was threefold higher than that for placebo at 96 weeks. Using an intent-to-treat, or ITT, analysis set, which treats any missing data as nonresponders, the 50-milligram EFX group at 49% remains significantly different from placebo at 19%, with the 28-milligram group showing a trend towards improvement in fibrosis at 30%. A reversal of at least 1 stage in fibrosis, which, by definition, includes both patients who have also experienced a 2-stage improvement in fibrosis, is reasonably expected to improve clinical outcomes in a long-term study. Slide 8 highlights how the response to EFX was sustained and expanded with increasing duration of treatment. Starting on the left, looking at placebo, the majority of responses at week 96 appeared to be new, which is not sustained from the previous analysis of histology at week 24. In contrast, for the week -- for the EFX 50-milligram group, the majority of responses at week 24 persisted through 96 weeks, and the response expanded considerably with 10 more new responders by week 96, meaning an unprecedented 75% of patients experienced an improvement of fibrosis without worsening of MASH. Similarly, for the EFX 28-milligram group, the majority of responses at week 24 persisted through 96 weeks with 2 additional new responders. Moving to the tables on the right. Among the patients who completed 96 weeks, the proportion of week-24 responders who sustained their improvement in fibrosis through week 96 was much higher at 92% and 83%, respectively, for the 50 and 28 milligrams than placebo at 40%. The proportion of new responders at 96 that had been previously nonresponders at week 24 was 63% for the 50-milligram dose group. Slide 9 places the fibrosis improvement observed after 96 weeks of treatment with EFX in the competitive landscape. Information relevant to interpreting each data set is provided above the corresponding histograms. These differences in trial design, patient populations and other factors mean cross-trial comparison should be viewed with caution since no head-to-head trials comparing these agents have been conducted. Needless to say, we believe the 75% response rate and the 52% placebo-adjusted effect size for the 50-milligram EFX set EFX apart. Slide 10 highlights how the response to EFX with deepening [indiscernible] with increasing duration of treatment. Here, we report the results for the week-96 endpoint of fibrosis improvement of 2 or more stages without worsening of MASH. Both EFX treatment groups were significantly better than placebo, with a response rate of 36% for 50 milligrams and 31% for 28, at least tenfold higher than that of the placebo at 3%. The statistical significance of this degree of fibrosis improvement is further supported by the corresponding ITT analysis. Approximately 1/4 of F2 patients fully resolved their fibrosis, i.e., went from fibrosis stage 2 to 0 after 96 weeks of EFX treatment. Slide 11 places the observed fibrosis improvement of 2 stages or more without worsening of MASH in the competitive landscape. As noted on the previous slide, cross-trial comparison should be viewed with caution since there's currently no head-to-head trials comparing these various investigational agents. As you can see here, low-dose semaglutide had a lower response rate than EFX, while the high dose was only 4% higher than the 22% placebo rate. The placebo rate for resmetirom and EFX were [ 43% ]. However, whereas response rate for resmetirom's treatment arms were about 3x higher than placebo, the response rate for EFX were more than tenfold higher than placebo. Turning to Slide 12. The population enrolled in HARMONY covers MASH patients with F2 and F3 fibrosis, with F3 comprising approximately 70% at baseline. The more advanced F3 fibrosis stage is generally considered more challenging to reverse than F2 and at a greater risk of progressing to cirrhosis. Here, we present a subset analysis of F3 patients from the HARMONY study, showing the rate of fibrosis improvement of 1 or more stages without worsening of MASH. The response rate of 68% for the 50-milligram EFX group was significantly higher than that of placebo at 14%, as was the response rate for the 28-milligram dose group at 40%. Here, we've broken out the relative contribution from 1- versus 2-stage improvement amongst F3 MASH patients. All of the F3 responders on placebo experienced the 1-stage improvement without worsening of MASH. By contrast, the majority of responses in both EFX groups were 2-stage improvements in fibrosis. We believe reversing from F3 to F1 fibrosis is likely to reduce progression to cirrhosis. Slide 13 reports the proportion of patients with MASH resolved with no worsening of fibrosis among patients who completed 96 weeks of EFX treatment. Levels of MASH resolution with no worsening of fibrosis were more than twofold higher at 57% and 62%, respectively, for the 50-milligram and the 28-milligram and significantly different from placebo at 24%. The corresponding ITT analysis further supports the statistical significance of these improvements for 50- and 28-milligram EFX groups relative to placebo. Slide 14 shows the percentage of patients in each group to achieve both fibrosis improvement of at least 1 stage and MASH resolution at 96 weeks. The response rate of 54% and 42% for the 50-milligram and 28-milligram EFX groups, respectively, were significantly greater than that of placebo at 9%, representing six- and fourfold higher response rates relative to placebo. Once again, statistical significance was maintained under an ITT analysis. We're encouraged by the [ strict ] strength of our histology results and what they may mean for our ongoing Phase III SYNCHRONY study. We believe demonstrating that a substantial proportion of patients experienced reversal of fibrosis after 96 weeks of treatment appears to differentiate EFX from therapies aimed at reducing body weight. Based on the results reported for patients whose body weight was reduced by 10% after a year, whether by improved lifestyle or gastric bypass surgery, it appears to take much longer than 2 years to improve fibrosis at the level of improvement observed after treatment with 50 milligrams of EFX over 96 weeks in HARMONY. We attribute the faster response of EFX to, firstly, its direct antifibrotic mechanism of action as demonstrated in preclinical studies; and secondly, its rapid resolution of MASH, which [ unraveled ] after 24 weeks of treatment in the Phase II study, comparable to those observed after a year of weight loss therapy. Slide 15 shows the effect of EFX on noninvasive markers of liver fibrosis, which are measurements of the status of the whole liver and are complementary to histopathology. On the left, we report change from baseline and the enhanced liver fibrosis, or ELF, score, derived using an algorithm based on 3 serum biomarkers indicative of rates of soft tissue, extracellular matrix deposition and turnover. The ELF score has been shown to correlate with the 1-stage improvement of fibrosis and cirrhosis. Here, we see statistically significant reductions of 0.7 and 0.8 across the EFX groups compared to a 1% reduction for placebo. A reduction of 0.5 has been reported to correlate with reduced progression to cirrhosis for patients with F3 fibrosis. The middle chart reports change from baseline for pro-C3, a serum marker of synthesis of new soft tissue, fibrillar type III collagen, indicative of fibrogenesis in the liver. Here, we see statistically significant reductions of 40 to 50 micrograms per liter across the EFX group compared to a decrease of 7 micrograms per liter for placebo. This translates to relative reductions of 24 -- sorry, 23% to 34%, well above the 20% reduction that has been previously correlated with a 1-stage improvement in fibrosis. The chart on the right reports change from baseline for liver stiffness, measured by transient elastography using a FibroScan instrument. Here, we see reductions of 4 to 7.2 kilopascals across the EFX groups are roughly 20% to 39% compared to a decrease of 0.6 kilopascals for placebo. In previous study of reduction in liver stiffness of greater than 20% or greater and equal to 25% was associated with fibrosis regression. The beneficial impact on liver health associated with the substantial improvement in liver histology following treatment with the EFX for 96 weeks is illustrated on Slide 16, which shows the EFX rapidly and sustainably lowered serum ALT and AST clinical markers of liver injury. Statistically significant reductions for both EFX groups were observed at all but 1 time point from week 4 through week 96, reflecting EFX rapid and direct alleviation of hepatocyte stress. At week 96, there were dose-related reductions in ALT of 37% to 44% for the EFX group compared with a reduction of 10% for the placebo. For AST, we see statistically significant similar rapid and sustained dose reductions from week 4 through week 96. Taken together, the significant results from both histology-based endpoints and noninvasive measures of whole liver fibrosis and injuries suggests that EFX has the potential power to reverse patients with MASH out of advanced fibrosis towards a healthy liver. Let's shift now to treatment-emergent adverse events summarized on Slide 17. The overall safety and tolerability looks similar to what was reported during the week-24 analysis. This table represents the entirety of the safety data through week 96, including what was previously reported. Starting at the top of the table shown here, there was no death in the study. A total of 15 serious adverse events were reported, which were relatively balanced across the treatment group and reflect the complex comorbidities of this advanced MASH population. Only 2 of these SAEs were drug-related. As previously reported for the 24-week data, 1 patient in the 50-milligram group had an SAE of esophagitis. After week 24 and through week 96, there were 3 new EFX-treated patients who discontinued due to drug-related adverse events, 1 case of diarrhea in each of the 28-milligram and 50-milligram group along with a reported case of pancreatitis, which was reported as an SAE. In the latter case, the diagnosis appears questionable since imaging failed to confirm as pancreatitis and the associated symptoms resolved quickly within 24 hours. The bottom portion of the table presents an overview of the most frequent drug-related treatment-emergent adverse events. Consistent with previous evaluations of EFX, the most frequent adverse events were transient, mild-to-moderate gastrointestinal grade 1 or 2 event. The majority of the injection-site reactions were mild, grade 1, and there were no discontinuations due to injection site reactions. As reported in previous studies, even though increased appetite was reported as an adverse event, mean body weight trended lower across EFX dose groups. Slide 18 containing the safety overview. No statistically significant changes were observed for heart rate, diastolic or systolic blood pressure at week 96. Markers of liver injury and hemostasis remained stable over the 96 weeks of treatment. The number of patients that progress to cirrhosis was low and balanced across treatment groups. Moving on to bone health. For context, many of the patients enrolled in HARMONY were women in the postmenopausal age group. The expected bone loss in this population described in the literature is around 1% to 1.5% per year. Therefore, a 2% to 3% decline over 96 weeks is expected in this demographic. At week 48, there was no statistically significant changes versus placebo at either the lumber spine or the femoral neck region of the head. At week 96, small reductions in the bone mineral density were observed in the EFX dose groups versus placebo in the lumber spine region of 3% to 4% and in the femoral neck region, which was less than 3% and it was only for the 50-milligram dose group. Unexpectedly, the placebo group experienced a 1% increase in the lumber spine region, which led to the statistical difference. I'll now turn the presentation over to our Chief Scientific Officer, Tim Rolph, who will present our biomarker data.

Thank you, Kitty, and good morning, everyone. The sustained improvements in liver health and histopathology after 96 weeks of treatment are underpinned by restoration of health in metabolism at a whole-body level. Starting with markers of lipid metabolism, Slide 19 shows that triglyceride levels are reduced significantly by almost 30% for the 50-milligram EFX group from baseline when adjusted for placebo change. Lower levels of triglyceride were associated with a 5% reduction in non-HDL cholesterol for 50 milligrams EFX relative to placebo. Levels of HDL cholesterol were increased significantly by 22% relative to placebo for 50-milligram EFX, while levels of LDL cholesterol were effectively unchanged by comparison with placebo. The pattern of changes for 28-milligram EFX were similar to those with 50-milligram but tended to be smaller. The improvement in lipoprotein profile is qualitatively similar to that observed after 24 weeks treatment, albeit the magnitude of improvement was somewhat smaller. Slide 20 presents the effects of 96 weeks treatment with EFX on markers of insulin sensitivity for all completers, including patients with and without type 2 diabetes. The most widely used measure of insulin sensitivity, HOMA-IR, indicated a statistically significant reduction in insulin resistance or 40% from baseline for 50-milligram EFX relative to placebo. Consistent with this, the level of insulin secretion was reduced by 28% from baseline for 50-milligram EFX relative to placebo. Another accepted indicator of insulin sensitivity, adiponectin, was increased significantly by 46% over baseline for 50-milligram EFX relative to placebo. The pattern of changes for 28-milligram trended in a similar direction but was smaller and not statistically different from placebo. Moving to Slide 21. As in previous studies, treatment with 50-milligram EFX was associated with the trend to mean body rate loss of 3.5 kilograms, with 28-milligram appearing to be weight neutral. The improvements in markers of metabolic health up to 96 weeks of treatment with 50-milligram EFX confirm a pattern seen across the preceding 5 independent studies in MASH patients with F1 to F4 fibrosis, of whom 2/3 or more have type 2 diabetes. In particular, improving sensitivity through insulin is essential to relieving the burden on the liver of excessive energy, which underlies steatohepatitis and the development of fibrosis. Sustaining these metabolic benefits over 96 weeks gives us confidence that the 50-milligram dose of EFX will again deliver the improvements in liver health, including regression of fibrosis in the SYNCHRONY Phase III program, which commenced enrolling in late 2023. I'll now hand the presentation back to Andrew.

Thank you, Tim. Turning to Slide 22. Let me offer a few concluding remarks with a focus on the EFX 50-milligram dose group. The large EFX responses on histology measures and the magnitude of statistical significance reported today far exceeded our expectations for a study with a sample size of only 88 biopsies at week 96. Here are the key takeaways from the HARMONY study. First, we believe the results reported for at least 1-stage improvement in fibrosis with no worsening of MASH are unprecedented. 75% of patients treated with 50-milligram EFX met this endpoint compared with 24% for placebo, with a p-value of less than 0.001. Second, EFX has been shown to have a deep impact on fibrosis. 36% of patients treated with EFX 50-milligram experienced a 2-stage improvement in fibrosis with no worsening of MASH, 12x the placebo rate of 3%, again, with a similar p-value of less than 0.001. Third, EFX was shown to have broad effects. 63% of patients who had not yet experienced a 1-stage improvement of fibrosis with no worsening of MASH after 24 weeks converted to treatment response at week 96 compared with 20% for placebo. Fourth, EFX was observed to be durable. An impressive 92% of week-24 responders treated with EFX 50 milligrams sustained their treatment response at week 96 compared to 40% for placebo. Finally, EFX has been observed to have high rates of treatment response among patients with advanced F3 fibrosis. 68% of patients treated with EFX 50 milligrams with F3 fibrosis at baseline and a week-96 biopsy had at least 1-stage improvement of fibrosis without worsening of MASH compared to 14% for placebo, once again at a p-value of 0.001. We believe these are the attributes of an investigational mass drug with the potential to have a transformative impact on patients' lives, if approved for marketing. Before closing, I'd like to take a moment to extend our gratitude to all of the investigators, study site staff and patients who participate in the HARMONY study. Today's exciting data would not have been possible if it were not for the dedication of our investigators, their teams and our patients. I'd like to turn things over to the operator for questions and answers.

[Operator Instructions] Our first question comes from Michael Yee with Jefferies.

Congrats on some great data. We had 2 questions. One on efficacy, given what you've seen and how things significantly improve over time. What are the -- what do you think the read-through is here to what is also ongoing in your F4 cirrhosis study? And how do you think about the implications for cirrhosis patients? And then the second question is on safety. On bone mineral density, I know Kitty made a couple of comments. Can you just sort of repeat what you said there and whether these patients [ would have been ] progressing anyways and whether there would be any ability to control for that in the Phase III?

So Mike, maybe I'll start and just say, when we think about the read-through, obviously, different patient population, different fibrosis burden overall. That being said, we're certainly encouraged by the results we see today, and we'll continue to watch as the story develops. I'm sorry, I couldn't be more specific. Maybe Kitty, do you want to maybe go back to your script and just clarify for Mike?

Sure. So Mike, I think what we saw in this study was the patients coming in to HARMONY, come in, unfortunately, with relatively poor bone health. And I think that's probably because of the patient population in general. Like I said, this was a large number of women on that sort of postmenopausal age group. I think you -- unfortunately, at that point in life, those women are expected to see bone loss over time. And that's what we know from the literature. It's approximately 1% to 1.5% per year. And so the decreases that we see in the HARMONY study in terms of the ranges are not really that surprising. I think the one aspect that was surprising was that we saw in the lumbar spine region that the placebo response actually increased by 1%, and that's really what led to the statistical significance in that group at 96 weeks.

Our next question comes from Eric Joseph with JPMorgan.

Let me also add my congrats on these data. A couple of questions from us. Notwithstanding that you have stat-sig fibrosis benefit on an ITT basis, I'm just wondering how we should be thinking about those patients that were absent from the liver biopsy analysis set going from 24 to 96 weeks. I guess were patients lost a follow-up or perhaps just unwilling to undergo a repeat biopsy? And I'm asking just to get a better sense of the longer-term compliance profile on EFX. Secondly, just circling back on this bone loss impact. I guess were there any imbalances that may have contributed to the delta? And ultimately, how are your study investigators looking at that impact and the ability to manage it in practice? And I guess -- or [ what happens here ] in the Phase III study? Are you perhaps pursuing to kind of further assess and perhaps mitigate some of that relative bone loss?

Yes. So Eric, maybe I'll start with the second question just on bone. I think it's something that as we look at over 2 years, as Kitty mentioned, the amount of bone expected in this population is roughly -- basically over 2 years, 2% to 3%. And that being said, the investigators will be following BMD in Phase III, and we expect we will share the results with the investigators, and we encourage them to -- there are multiple therapies available for bone loss. If they experience bone loss, we encourage them to seek endocrinologist consults as well as appropriate treatment. And then maybe for the question for a patient disposition, Kitty, do you want to touch on that? For those who didn't make it to week 96 but made it to week 24?

Yes. So really to respond to your question, Eric, I mean, I think what you can see is that between week 24 and week 96, we had very few patients who actually discontinued due to adverse events. It was only 3 patients, as we mentioned. The rest of the discontinuations really fall under the category of administrative. And so that falls into things like patients that withdrew consent or when lost to follow-up. And I think it's really in relation to patients having to attend [ classic ] clinic visits weekly over 96 weeks across the treatment groups. And so when I look at the administrative discontinuations, it was 6 on the placebo group. There was 7 on the 28-milligram group. And I think it was just 2 on the 50-milligram dose group, but that really explains the patients that didn't have week 96 biopsies just really because they were no longer willing to participate in the study for those reasons.

Our next question comes from Mike Ulz with Morgan Stanley.

Congratulations on the data as well. Maybe just 2 for me. So just starting with fibrosis, you mentioned the 50-milligram arm. I think there were 10 additional fibrosis responders post the 24 weeks. Just curious if there's anything unique about those patients, for example, were they more like F3 patients versus F2, for example? And then maybe secondly, just given the robust effects you're seeing at the 50-milligram dose arm, do you still think you need to evaluate the 28 milligrams in Phase III?

Yes, Mike, I think with the second one, I think it's something that we're reflecting on in light of these data at -- something, obviously, we'll be discussing in consultation with the agency. So I don't think we have a lot to say at this point. We're certainly taking a look at the totality of the data. And then in terms of your first question about looking into specific characteristics of the 10 patients on the 50-milligram group that really developed that 1-stage improvement in between week 24 and week 96, I think this is something that on an individual patient level, we're still digging through. These data are very fresh, and I don't know that we have a specific understanding of all the characteristics defining those folks. Unless Kitty, did you have anything else to add?

No. Although I would say that maybe we weren't that surprised by this, Mike. When we had looked at the data after 24 weeks, we knew from an analysis performed by our pathologist that even in patients who didn't, at week 24, reach a 1-stage categorical improvement in fibrosis, there was a number of patients that had these what pathologists described as patterns of regression, although just not quite meeting that 1-stage improvement of fibrosis. And I think now looking back at what's clear that those patients just needed longer treatment duration to reach that 1-stage categorical improvement. And so that's what we're seeing at week 96.

Got it. That's helpful. Congrats again.

Our next question comes from Liisa Bayko with Evercore ISI.

Congratulations on the data. I just wanted to ask sort of a slightly different question in terms of progression to forward. So have you looked at the data in terms of stabilization versus any patients who did progress to either cirrhosis or F3 from F2 or F3? I'd be curious on that kind of like ability to stabilize versus placebo.

Kitty, do you want to just -- maybe the easy way just to start with the cirrhotics?

Yes. So maybe I'll start, Liisa. So in terms of progression to cirrhosis, the numbers were very small. And so it's going to be difficult for us to see anything particularly meaningful of that, and it was balanced across the treatment groups. When we look at the broader data in terms of progression, including those going from F2 to F3, that data that, I think, is going to be interesting, and it's something that we'll present an upcoming scientific conference. And so there's not really more data that we're going to share about that today.

Thank you. That's all the time we have for questions. This does conclude our presentation. Thank you for your participation. You may now disconnect. Everyone, have a great day.