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

Good morning, ladies and gentlemen, and welcome to the Akero Therapeutics conference call to review results for the recently concluded SYMMETRY Cohort D study. As a reminder, today's conference call is being recorded. I'd now like to turn the conference over to Bill White, Akero's Chief Financial Officer 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; Tim Rolph, our Chief Scientific Officer; Jonathan Young, the Chief Operating Officer; and Patrick Lamy, Senior Vice President of Commercial Strategy. Today, we will be sharing top line results from a 12-week expansion cohort of the Phase IIb SYMMETRY study known as Cohort D, evaluating efruxifermin or EFX for short, in combination with the GLP-1 receptor agonist or GLP-1 for short, in patients with NASH and type 2 diabetes. Before we begin, I ask that you please read the disclaimers presented on Slide 2, and we'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 express or implied statements regarding implications of this analysis of the SYMMETRY study or 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 that 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 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 covering data from our Cohort D study, which is available on our website at akerotx.com under Press Releases in the Investor Relations section. The presentation will 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 have joined today's webcast. We initiated this expansion cohort to assess whether EFX could be added in patients with NASH, who are already being treated with GLP-1 for type 2 diabetes mellitus. This was an important question for us to address because approximately 2/3 of patients with F2 or F3 NASH have type 2 diabetes. The primary purpose of this study was to determine if EFX could be added with acceptable tolerability for patients already receiving a GLP-1. Both medicines used alone are associated with more frequent gastrointestinal side effects. The secondary purpose was to assess whether the potential for EFX combined with GLP-1 to offer treatment benefits for NASH patients more than GLP-1 alone. Although NASH with fibrosis stages F1 through F3 was confirmed for each patient enrolled in Cohort D, the secondary endpoints were based on noninvasive measures covering markers of liver steatosis, injury and fibrosis. Markers of whole body glycemic control and lipid metabolism were also evaluated. Here's the bottom line. The safety and tolerability of EFX dosed to patients in combination with the GLP-1 therapy was broadly comparable to that of placebo-treated patients receiving GLP-1 therapy alone. In addition, no new safety signals were evident. The study thus met its primary endpoint of demonstrating acceptable safety and tolerability with the addition of EFX to existing GLP-1 therapy. In all markers of liver health and fibrosis presented today, EFX combined with the GLP-1 therapy, was more effective than GLP-1 alone, in most cases, significantly so despite the modest study size. Likewise, glycemic control and lipid profiles were improved more in the combination of EFX with GLP-1. The data we report today exceeded our expectations for Cohort D. We believe EFX has the potential to provide substantial benefits for the many NASH patients who have type 2 diabetes mellitus and are being treated with GLP-1 therapy. I'll now ask our Chief Development Officer, Kitty Yale, to dive into more detail on today's data.

Thank you, Andrew, and good morning, everybody. I'm thrilled to report the 12-week results from Cohort D. Let's begin by reviewing the design of Cohort D, which is shown on Slide 4. Cohort D is an expansion of the Phase IIb SYMMETRY study, a randomized double blind placebo controlled trial in patients with biopsy-confirmed NASH. Although the main SYMMETRY study is evaluating EFX in patients with cirrhosis due to NASH, Cohort D takes the EFX in patients with biopsy-confirmed fibrosis stage 1, 2 or 3. All patients enrolled in Cohort D were required to have been on a stable dose of GLP-1 therapy for at least 3 months prior to entering into the study. In fact, approximately 2/3 of all randomized patients have been receiving GLP-1 therapy for a year or more. Patients were randomized to receive once weekly subcutaneous doses of either 50 milligrams of EFX or placebo in combination with their baseline GLP-1 therapy. The primary endpoint evaluated safety and tolerability over 12 weeks of treatment. While Cohort D was a small study and was not statistically powered for comparisons of efficacy, a set of secondary endpoint -- sorry, a set of secondary endpoints were prespecified for comparison of EFX combined with GLP-1 -- compared to GLP-1 alone. These included change from baseline to week 12 for noninvasive markers of liver steatosis, injury and fibrosis. In addition, given the potential of GLP-1 and EFX to have complementary effects on whole-body metabolic health, markers of glycemic control and lipid metabolism were analyzed as was change in body weight. We believe improvement to overall metabolic health will be a critical consideration to regulatory authorities as they review the overall risk-benefit profile of investigational NASH drugs. Before diving into today's exciting results, let's review the study disposition and the analysis set used for today's presentation. As shown on Slide 5, 32 patients were randomized. One patient randomized to the placebo arm was not dosed. The full analysis set and the safety set are [ compromised ] (sic) comprised of 31 randomized patients who received at least 1 dose of investigational product. Two patients both in the EFX treated group discontinued prior to week 12. One discontinuation was due to withdrawal of consent and the other was for nausea. Consequently, 10 placebo patients and 19 EFX treated patients completed 12 weeks of treatment. On Slide 6, we review baseline demographics. Most patient measurements were comparable between the 2 treatment groups. However, the placebo group had a higher proportion of females and patients with F3 fibrosis as well as a higher baseline level of liver fat. Baseline hemoglobin A1c was lower in the placebo group. Not surprisingly, given GLP-1's well-documented effects in liver steatosis, type 2 diabetes and body weight, some of the baseline measures in Cohort D were lower than seen in our previous BALANCED and HARMONY study. For example, mean baseline liver fat content was appreciably lower and levels of AST and ALT were within the standard reference ranges. On Slide 7, we report baseline medications for type 2 diabetes. The top of the table identifies the baseline GLP therapies that were taken during Cohort D. The doses of GLP-1 therapy were within the labeled range for treatment of type 2 diabetes. Other antidiabetic medications were also required to have been stably dosed for 3 months prior to entering the study, and they are summarized in descending order at the bottom portion of the table. Patients in the EFX treated group were generally more intensively treated with diabetic medications than those in the placebo group. Let's dive into the data. We report results for the primary endpoint of safety and tolerability on Slide 8. There were no deaths in the studies, and no patients were reported to have drug-related serious adverse events. There was 1 patient who discontinued due to nausea -- and that was -- the patient was treated with EFX. Consistent with previous evaluations of EFX, gastrointestinal events were the most frequently reported adverse events. The overall tolerability profile was similar to what was observed with EFX in our previous BALANCED and HARMONY studies. Diarrhea was more frequent in the GLP alone group than the EFX combined with GLP group, while nausea was slightly more frequent in the combined group than for GLP alone. Both treatment groups reported decreased appetite and more EFX treated patients reported increased appetite. However, there was overall a mean reduction in body weight observed for EFX treated patients despite the reports of increased appetite. As we turn our attention to secondary efficacy endpoints, we note that overall, the combination of EFX and GLP-1 yielded marked improvements relative to GLP alone, even though Cohort D was not powered to demonstrate statistically significant differences on these endpoints. Slide 9 shows the relative reduction in liver fat observed after 12 weeks. An impressive 65% relative reduction was observed for EFX plus GLP-1 compared with 10% for GLP-1 alone. Slide 10 puts this magnitude of reduction in context by comparing it to decreases observed for the preceding HARMONY and SYMMETRY studies as well as for studies with key competitor investigational therapies. Even though cross-trial comparisons cannot be made due to important trial differences, including all of the design features summarized here, we think these results provide useful cohort context ends for Cohort D data. Baseline liver fat is denoted above each histogram. A higher baseline for liver fat allows more scope for relative reduction. As seen here, Cohort D has the lowest mean baseline lever fat at 11%, the others range from 17% to 20%. Despite less scope to reduced liver fat and the fact that patients entered the study on GLP-1 therapy, which has been shown to reduce liver fat, the 65% relative reduction for EFX is greater than all but one of the competitor investigational therapy shown here. The 65% relative reduction observed with the addition of EFX versus the 10% relative reduction with GLP alone highlights EFX' potential to suppress liver fat even further for patients taking a therapy that has already appreciably decreased their liver fats. A fuller perspective on the extent of liver fat reduction following EFX treatment is provided on Slide 11. As shown in the far left panel, 88% of patients treated with EFX normalized their liver fat. So that means reduced it to less than 5% during the 12-week treatment period, compared to just 10% for the placebo group. Analysis of prior studies with EFX have revealed that the probability of resolving NASH and improving fibrosis by one stage is threefold more likely when lever fat was normalized. The center and right panels show how liver fat normalization was achieved following treatment with EFX. Liver fat was reduced by more than 50% in 88% of patients treated with EFX compared to 0% for placebo. And despite a mean baseline absolute content of 11%, 56% of patients met an even higher threshold of greater than 70% relative reduction after treatment with the EFX compared to 0% for placebo. Given the correlation between liver fat normalization and the regulatory endpoint of NASH resolution and one-stage fibrosis improvement that we observed in the HARMONY study, we are encouraged that nearly 9 out of 10 treated EFX patients normalized their liver fat within just 12 weeks of treatment in Cohort D. Slide 12 shows the effects of EFX on noninvasive markers of liver fibrosis. Previous studies with EFX have shown consistent reductions in these markers as well as significant improvements of fibrosis assessed by histopathology. The leftmost panel showed a change from baseline for the serum marker PRO-C3, indicative of new collagen synthesis in the liver. The reduction was statistically significant versus baseline for EFX added to GLP-1, but not for GLP-1 alone. The next panel shows change from baseline for enhanced liver fibrosis, or ELF score, which is derived using an algorithm based on 3 serum biomarkers indicative of soft tissue fibrosis deposition and turnover. There was a statistically significant reduction of 0.6% for EFX compared to an increase of 0.1% for placebo. A reduction of 0.5% has been reported in other longer-term studies to correlate with a one-stage improvement in fibrosis. The panel right of center shows change from baseline for liver stiffness as measured by transient elastography using FibroScan. There was a statistically significant reduction versus baseline of 16% compared with about 2% for the GLP alone. The rightmost panel shows the FAST score. This score combines the liver stiffness with controlled attenuation parameter or CAP score and AST to identify patients at higher risk of NASH progression. We observed a significant reduction for the EFX group, reflecting a higher proportion of patients who moved to a lower FAST -- lower risk FAST category. These results for noninvasive markers are important because they show the ability of EFX to accelerate regression of fibrosis for patients already receiving GLP-1. Let's shift to markers of liver injury, which are shown on Slide 13. As mentioned previously, mean ALT and AST levels for patients entering Cohort D were mainly within the reference range at baseline. Nonetheless, adding EFX to GLP-1 for 12 weeks resulted in significant reductions in these markers of liver injury. Liver enzymes were unchanged or slightly increased for the placebo group. In sum, we believe the changes in noninvasive measures of whole liver steatosis, injury and fibrosis reinforce EFX' potential to resolve the steatohepatitis and to reverse fibrosis for patients with NASH when used in combination with existing GLP-1 therapy. I would now like to turn the presentation over to our Chief Scientific Officer, Tim Rolph, who will present additional biomarker data.

Thank you, Kitty, and good morning, everyone. Restoring metabolism in the whole body through a healthier status is essential for establishing an environment to support the liver as steatohepatitis resolves, fibrosis regresses and the population of hepatocytes regenerates. The improvements in liver health associated with EFX treatment combined with GLP-1 suggests healthy metabolism is substantially restored at a whole body level, which we review, starting with Slide 14. Although GLP-1 is known to be effective in improving glycemic control, combining EFX with GLP-1 was observed to result in greater reductions in hemoglobin A1c. As shown in the left [Technical Difficulty] reduced HbA1c significantly by 0.5% relative to baseline compared to 0.2% for GLP-1 alone. The greater impact for the combination translated into almost 1 in 4 EFX treated patients normalizing levels of hemoglobin A1c below 6.5%. EFX improves glycemic control by complementing the insulin secreting action of GLP-1 therapy. EFX increases sensitivity of metabolic organs or tissues to insulin, in effect enhancing the ability of insulin released by GLP-1 to promote blood glucose uptake by, for example, adipose tissue. Increased insulin sensitivity leads to reduced secretion of insulin from the pancreas, which can be measured through the marker of C-peptide. As indicated in the left panel of Slide 15, EFX treated patients experienced a significant 22% fall in C-peptide level. Further evidence of efruxifermin's insulin sensitizing well is seen in the numerically greater decrease in levels of insulin after 12 weeks of treatment with EFX, as shown in the center panel. In the longer term, we believe reduced insulin secretion could help to preserve pancreatic function, thereby delaying the need for treatment with insulin and improving the prognosis of the patients. By enhancing insulin-dependent [ glucose ] uptake and nutrients -- and storage of nutrients by adipose tissue, EFX redirects energy away from the liver. This, in turn, enables the liver to use its excess stores of energy, particularly fat droplets that may otherwise contribute to NASH progression. Finally, the right panel shows a significant increase in the Adiponectin, another marker of insulin sensitivity. Adiponectin also serves as a marker of the pharmacological action of EFX on adipose tissue. Levels increased by 129% for EFX combined with GLP-1 compared to minimal change for GLP-1 alone. Restoring healthy whole-body metabolism not only requires better glycemic control but also improved lipid metabolism. Slide 16 shows change from baseline for serum levels of a number of key lipoproteins. As shown here, the EFX combined with GLP-1 improved lipoprotein profiles beyond what was achieved by treatment with GLP-1 alone prior to study start. Starting at the left panel, the level of triglyceride was reduced significantly by 42% for EFX compared to minimal change for GLP-1 alone. The next 2 panels showing results for non-HDL cholesterol and apolipoprotein B, are important for NASH patients with elevated triglyceride level because these measures are considered better predictors of overall risk of cardiovascular disease than LDL cholesterol. Here, we see a significant reduction versus baseline for non-HDL cholesterol of 19% for EFX combined with GLP-1 compared to a decrease of 7% for GLP-1 alone. Moving to the center panel, apolipoprotein B is significantly reduced by 21% after treatment with EFX and GLP-1 compared to a 5% reduction for GLP-1 alone. In the next panel, treatment with EFX and GLP-1 was associated with modestly lower levels of LDL cholesterol similar to GLP-1 alone. On the other hand, levels of HDL cholesterol increased significantly by 38% after treatment with EFX combined with GLP-1 compared to minimal change for GLP-1 alone. To put the clinical benefit of these improvements in lipoprotein profile in context, up to 80% of the NASH subjects are reported to be dyslipidemic. Dyslipidemia is a substantial contributor to the high incidence of cardiovascular disease among NASH patients, which is the main cause in mortality. In summary, we observed that in Cohort D, the lipoprotein profile of NASH patients was improved substantially more by the combination of EFX with GLP-1 than by GLP-1 alone. Moving on, Slide 17 shows change in body weight. Induction of weight loss is, of course, one of the major benefits of GLP-1 therapy. Here, we see that adding EFX to GLP-1 was associated with continued weight loss of 1.2 kilograms after 12 weeks comparable to the 0.8 kilogram loss for GLP-1 alone. After accounting the differences in baseline levels, these very encouraging improvements in metabolism in Cohort D are generally comparable to those observed in the BALANCED and HARMONY studies. Four independently conducted studies of EFX in patients with F1 to F4 NASH have now shown a consistent pattern and the magnitude of improvements in markers of liver health and whole-body metabolism. This consistency increases our confidence that we will continue to see favorable results in the ongoing Phase IIb SYMMETRY study as well as in the upcoming Phase III SYNCHRONY studies. Before handing the presentation back to Andrew, I'd like to offer a few thoughts on the relative potential of GLP-1 and EFX to reverse NASH fibrosis. As a reference point for patients with NASH, loss of 10% or more of body weight, whether after bariatric surgery or adoption of a healthy lifestyle, is associated with substantial resolution of NASH after a year, but regression of fibrosis takes much longer, up to 4 to 5 years. Rates of NASH resolution and fibrosis regression with GLP-1 therapy, as reported in other clinical trials, appear to be following a similar time scale and pattern. This is consistent with the potentially beneficial effects of GLP-1 deriving largely from weight loss and improved whole-body metabolic health. In contrast to these slow rates of fibrosis regression, EFX appears to be improving fibrosis over an appreciably shorter time scale. In both the BALANCED and HARMONY studies, treatment with EFX was associated with evidence of significant fibrosis regression within 6 months. We believe this reflects 2 distinct actions of the EFX. One is direct inhibition of collagen synthesis in the liver, observed within 4 weeks of starting treatment. The other is more indirect, relying on the potential of EFX to normalize liver fat and to reduce stress, injury and death among hepatocytes, which in turn reduces profibrotic signaling. We believe this indirect inhibition of new collagen synthesis or fibrogenesis plays out over a longer time scale. We therefore expect that EFX given to patients already taking GLP-1 therapy has the potential to accelerate regression of fibrosis and to resolve NASH in a substantially greater proportion of patients. The medical need for patients with F2 or F3 NASH is to prevent them from progressing to cirrhosis or preferably reverse some [ out-of-liver ] fibrosis. We believe EFX has the potential to do this both as a monotherapy and when used in combination with GLP-1 therapy. I'll now hand the presentation back to Andrew.

Thank you, Tim. Cohort D focused on treatment with EFX in combination with GLP-1. Our primary objective was to determine whether these 2 compelling mechanisms had an acceptable safety and tolerability profile. We believe today's Cohort D results affirmatively addressed that question. As I mentioned at the beginning, these data far exceeded our expectations. We do not expect to see such strong across-the-board improvements for the combination of EFX with GLP-1 compared to GLP-1 alone. Especially noteworthy was normalization of liver fat at 12 weeks for 88% of patients treated with EFX in combination compared to 10% with GLP-1 alone. The success of GLP-1 as a treatment for both type 2 diabetes and obesity, which are highly prevalent among NASH patients, has led some to opine that GLP-1 will dominate treatment of NASH and to question whether other mechanisms can improve meaningfully on what GLP-1 offers. Today's results suggest that GLP-1 therapy alone is unlikely to be a sufficiently robust approach to treating a complex disease like NASH. EFX has the potential to provide substantial benefits for the many NASH patients who have type 2 diabetes mellitus and are already receiving GLP-1 therapy. Let me take a moment to review the status of our development program as summarized on Slide 19. Akero's next key milestone is the readout of our Phase IIb SYMMETRY study in patients with compensated cirrhosis due to NASH. We remain on track to report those results in the fourth quarter of this year. We've named our Phase III program, SYNCHRONY. The first planned studies are SYNCHRONY Histology and SYNCHRONY Real-World; the formers in patients with NASH fibrosis stages 2 and 3, the primary endpoint is to resolution of histopathology. The second is a real-world noninvasive study of patients with NASH fibrosis stages 1, 2 and 3. The primary end point is to be safety and tolerability. Protocols for both of these studies have been submitted to the FDA. We expect to initiate both studies during the second half of this year. Before closing, I'd like to take a moment to extend our gratitude to the investigators, study site staff and patients who participated in Cohort D. Today's exciting data would not have been possible were it not for the dedication of our investigators, their teams and the patients who participated. I'd now like to turn things over to the operator for questions and answers. Operator?

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

We had 2 questions. One was, Andrew, obviously, the efficacy here looks phenomenal in combination. We wanted to understand perhaps a little bit on the safety tolerability, maybe just talk a little bit about the nature of it. I think I see lower diarrhea rates, which is pretty remarkable in combination, but maybe slightly higher nausea. Just can you remind us on the onset or the nature of the nausea, particularly as chronic therapy in combination and then talk about how to think about that for EFX. And then second question, just really quickly was how to take these findings in the advanced, that is, are the diabetes patients in the background therapies allowed in Phase III and stratified or is that just a separate potential study? Maybe just remind us how you actually implement these findings.

So maybe I'll ask Kitty to sort of take those 2 in order. That would be great.

Sure. No problem. So Michael, I think what is really noticeable about the Cohort D data in terms of the safety and tolerability that it is incredibly consistent with what we've seen in BALANCED and HARMONY. And so really no surprises. And in terms of the GI adverse events, I think the one thing that we've always stated quite clearly that makes these events unique is that they're very transient. And so the patients have waves of either diarrhea or nausea, but it's not a constant event. They're mostly grade 1, some grade 2, and they do occur earlier in the treatment timeframe, where the one patient that did discontinue due to nausea, it occurred at week 2. And that's consistent with what we see in our other studies where any sort of GI adverse events seems to predominate in the first month of treatment. And then really after that time points, the patient find it very easy to continue on treatment. And they definitely abate over time. In terms of the Phase III program, we will continue with how we've designed our Phase IIb program, and we will allow patients to come into the study as long as they're on a stable GLP-1, and that has always been defined as like being on a stable dose for at least 3 months. We did have patients in both BALANCED and HARMONY that we're on GLP-1. The numbers were relatively low, though. It was just under 10% for BALANCED and just under 14% for HARMONY. But I think as we see the prevalence of these medications of growing globally, we do expect that we might have slightly higher numbers of patients on them within the Phase III program.

Very helpful. I do recall the onset was more in the first month and sort of mitigated. So very helpful.

Our next question comes from Eric Joseph with JPMorgan.

Thanks for this updated data. Given that patients had to be on stable GLP meds for at least 3 months prior to entry, do you have a sense of how their liver, lipid and fibrosis markers performed prior to entry? We've been a little bit surprised by some of the changes on the placebo arm on measures like Pro-C3 and LDL cholesterol. So I'm just wondering how we should be looking at those changes on the placebo arm, whether they're considered real or noise and how they might trend with longer follow-up perhaps in the Phase III program such as in SYNCHRONY. And then -- as it relates to just administration here in combination with the GLPs, can you just talk about sort of how -- what was called for in the protocol, whether they were administered with EFX -- whether the GLP, if GLPs and the EFX were set to be administered in company, at the same time with one another or in a staggered fashion? I'm just trying to think about sort of in the commercial side and how diabetes patients might be -- might seek to use the 2 agents in combination with one another on a scheduling phases.

So Eric, maybe just in general, I would -- it's difficult to know exactly what the trend would be in longer-term dosing since this was only a 12-week study. But I would say that it's important to note that 2/3 of the patients had already been on GLP-1 for at least a year. So I think really what you see, the bulk of the study really is likely -- the answer to your question is that with GLP-1s, you do see slightly lower liver enzymes than perhaps naive or new to therapy NASH patients we've seen in the past. But at the same time, I think the results of the study are quite robust because this is largely the trajectory that when we look at the results, it really shows that the GLPs, there's quite a bit more liver fat that can be moved in the combination. And so there is still quite a bit of room for improvement with the addition of EFX. And in terms of administration, Kitty can confirm, but I believe they were -- there's no instructions as to -- that they had to be administered simultaneously or at the same day, it's really at the discretion of the patient.

Andrew, that's correct. And we really wanted it to be sort of like a real-world setting. So there was no guidance given in terms of how the 2 were administered together.

Okay. Got it. Maybe just one follow-up, if I could, on weight change. You commented here on the mean difference in weight change. I'm just wondering if there's a -- really, if you could just kind of comment on the proportionality of patients who saw weight loss versus any who experienced weight gain with the combination and how that may have differed with -- how that compared with placebo or GLP-1 alone.

So Eric, at this point, we've just received the top line data. The individual patient data we have yet to receive, and that's sort of what you're asking, if we could have seen a histogram or individual patient plots of how the number of patients gained versus loss. Overall, we're just pleased that EFX compared well to a drug that's known for weight loss.

Our next question comes from Mike Ulz with Morgan Stanley.

Maybe a follow-up on an earlier safety question. Just in terms of the one patient that did discontinue due to nausea. Was there anything unique about that patient in terms of baseline characteristics, et cetera? And then secondly, if you can just talk a little bit about the patient numbers for some of the efficacy end points, specifically liver fat seems to be only 16 patients, but in some of the other analyses, there's a higher 21 patients?

Sure. Kitty, do you want to address the 16 versus 21?

Yes. So that was -- we had an issue, Mike, where there were 3 patients at one center where there -- we collected their baseline MRI-PDFF and then it was only after they were randomized that we realized that there had been an issue with the way they've been collected. We do actually have those patients. We had brought them back in and we repeated their MRI-PDFF, but was after baseline, so we didn't include them in the main analysis set. But at a future point, I mean, they were only 2 or 3 days after starting treatment. We'll be able to do another analysis and include those patients, but it was just that it was an administrative problem. And on the question about the patients that discontinued due to nausea, there was really nothing particularly unique about that patient. They did have a medical history of migraines that had been occurring prior to the patients coming into the study. And so I think just really was in that patient that was already suffering with migraines that they weren't comfortable with the nausea, but really nothing else unique about that patient.

We have time for one last question. And that question comes from Liisa Bayko with Evercore.

Most of them have been answered. I think the data shows that you have continued added benefit on top of GLP-1 and that's the bottom line. So how is that -- does this data in any way shaped your thinking of your Phase III plan? Any tweaks you want to make and how you think about including the GLP-1 patients? Will they be stratified in some way? Or is there a certain cap on how many -- what percentage you will allow? How you think about that cohort?

What I would say is that as we see these results, we're encouraged given the increasing use of GLP-1s in the world -- that EFX works so well. In the past, as Kitty mentioned on our previous question, we've always stratified by patients with type 2 diabetes. And I think we'll continue to do that in Phase III. So overall, we're encouraged as we are going forward given the increasing use of these agents. But in terms of immediate changes to the plan, I don't really foresee too many.

That's all the time we have for questions. Thank you for participating in today's program. This does conclude the conference. You may now disconnect. Everyone, have a great day.