Mirum Pharmaceuticals, Inc. ($MIRM)

Good morning, and welcome to Mirum Pharmaceuticals Business Update Call. My name is Ben, and I will be your operator today. [Operator Instructions] I would now like to hand the conference over to Andrew McKibben, SVP of Strategic Finance and Investor Relations. Please go ahead.

Thank you, Ben, and good morning, everyone. I'm very happy to welcome you to Mirum's conference call to discuss our recent clinical readouts, including the top line results of our VISTAS Phase IIb study of volixibat in patients with primary sclerosing cholangitis, or PSC, and last week's announcement of top line results from the Phase II portion of the AZURE-1 study of brelovitug in hepatitis delta. For our prepared remarks, I'm joined today by our CEO, Chris Peetz; and our Chief Medical Officer, Joanne Quan. I'm also joined by our President and Chief Operating Officer, Peter Radovich; and our Chief Financial Officer, Eric Bjerkholt, who will both be available for Q&A. The call will begin with opening remarks from Chris, followed by Joanne, who will review the clinical data. After prepared remarks, we will open the call for Q&A. Earlier today, Mirum issued a press release announcing the VISTAS Phase IIb study results. A copy of that release, along with the presentation summarizing these results is available on the Investors section of our website. Before we start, I'd like to remind you that during the course of this conference call, we will be making certain forward-looking statements based on management's current expectations, including statements regarding Mirum's programs and market opportunities for its approved medicines and product candidates and financial guidance. These statements represent our judgment and knowledge of events as of today and inherently involve risks and uncertainties that may cause actual results to differ materially from the results discussed. We are under no duty to update these statements. Please refer to the risk factors in our latest Form 10-K and subsequent SEC filings for more information about these risks and uncertainties. With that, I'd like to turn the call over to Chris. Chris?

Thank you, Andrew, and thanks to everyone joining our call today. It has been a busy couple of weeks for the Mirum clinical team. Today marks a defining moment for Mirum and more importantly, for patients living with PSC. We are very pleased to announce that the VISTAS study met its primary endpoint, demonstrating a statistically significant and clinically meaningful improvement in cholestatic pruritus for PSC patients treated with volixibat. These results represent the first successful demonstration of a therapy addressing a core symptom of PSC in a controlled study and position volixibat as a potential first approved medicine for patients. PSC is a progressive and highly burdensome condition with no approved therapies. For patients, pruritus is not a secondary concern. Along with fatigue, it is often one of the most debilitating aspects of the disease, impacting sleep, daily function and overall quality of life. These results highlight the potential for volixibat to meaningfully change the treatment paradigm in PSC. It is a transformational moment for Mirum as a company as this progress comes on the heels of the Phase IIb portion of the AZURE-1 study of brelovitug in hepatitis delta we shared last week. Our commercial team looks forward to the potential to bring both of these standard of care-changing medicines to patients. Before turning it over to Joanne to walk through the highlights of the VISTAS data, I want to also acknowledge the patients, investigators and advocacy groups who made this study possible. PSC is a challenging disease to study and their commitment is reflected in the strength of these results. Now over to Joanne. Joanne?

Thank you, Chris. I'm very pleased to review the results from the VISTAS study, and I will also take a few minutes to walk through the top line results of the AZURE-1 Phase IIb study we announced last week. First, I would like to extend my gratitude to the patients, investigators and study teams whose participation made this work possible. PSC is a chronic progressive cholestatic liver disease characterized by impaired bile flow, leading to the accumulation of bile acids and subsequent liver injury. Patients experienced fluctuating elevations in liver enzymes and progressive fibrosis, often accompanied by the development of biliary strictures and recurrent and unpredictable episodes of acute cholangitis that can require repeated endoscopic or interventional procedures to manage. PSC can ultimately result in cirrhosis, liver failure and the need for liver transplantation. PSC is also associated with a significantly increased risk of cholangiocarcinoma. Importantly, beyond disease progression, patients carry a substantial symptomatic burden, particularly cholestatic pruritus and fatigue, which meaningfully impacts daily functioning and quality of life. As a reminder, VISTAS is a Phase IIb randomized, double-blind, placebo-controlled study evaluating volixibat in patients with PSC and pruritus over 28 weeks. Patients with moderate to severe pruritus at baseline were placed in the primary cohort and patients with mild pruritus at baseline were evaluated in the secondary cohort. All patients were included in the safety evaluation. All patients were randomized to receive volixibat 20 milligrams twice daily or placebo. Baseline demographics and patient characteristics were well balanced across study arms in the primary cohort with a mean baseline itch score of about 6 out of 10, reflecting the severity of itch in this patient population. Consistent with PSC, slightly over 70% of patients had concurrent inflammatory bowel disease and baseline liver function tests were characteristically elevated and generally comparable across study arms. The primary endpoint evaluated the mean change from baseline in pruritus compared to the average of the last 12 weeks of treatment using a mixed effects model with repeated measures analysis. Pruritus was assessed using the Adult ItchRO, a once-daily 0 to 10 numerical rating scale with a score of 10 being the worst itch. I'm very pleased to say that volixibat demonstrated robust and statistically significant reductions in itch. Specifically, treatment with volixibat saw a 2.7 point reduction in itch score compared to a 1-point reduction for patients receiving placebo. This translates to a placebo-adjusted improvement of 1.64 points with a p-value of less than 0.0001. We believe this is an outstanding treatment effect and the magnitude of improvement is consistent with what we have observed in other cholestatic indications and reflects a meaningful benefit for patients. The safety profile of volixibat was consistent with the known effects of IBAT inhibition, characterized by gastrointestinal adverse events and changes in liver laboratory parameters such as alanine aminotransferase, ALT and total bilirubin. There were similar numbers of patients in both treatment groups with grade 3 or higher treatment-emergent adverse events, and there were no treatment-related serious adverse events. There were 8 patients in the volixibat group and 5 in the placebo who experienced serious adverse events. In general, these were reflective of the course of their underlying disease. There were 7 patients with treatment-emergent adverse events leading to premature study discontinuation in the volixibat group and 2 in the placebo group. Of the 7 patients in the volixibat group who discontinued the study, 3 were for diarrhea. 40% of patients on volixibat had treatment-emergent diarrhea compared to about 9% on placebo. Elevations in ALT, AST, ALP and bilirubin were observed more frequently in volixibat-treated patients than placebo-treated patients. This trial represents an important step toward bringing a potential first-in-disease treatment option to patients with PSC, and we are looking forward to presenting the full results as an oral late-breaking presentation at the EASL International Liver Congress at the end of May. We also plan to review these results with the FDA at a pre-NDA meeting scheduled for this summer. Following this interaction, we plan to submit an NDA in the second half of this year. Finally, a quick reminder on the recently announced Phase IIb portion of the AZURE-1 study, which also met its primary endpoint. AZURE-1 is evaluating treatment-naive hepatitis delta patients randomized to 300 milligrams once weekly, 900 milligrams once every 4 weeks or delayed treatment with a 24-week primary composite endpoint of biologic response and ALT normalization. This is an earlier time point than the 48-week Phase II brelovitug data previously shared at AASLD. In the first 53 patients evaluated at week 24, brelovitug demonstrated robust antiviral activity across both dose groups. With 100% of patients in the 300-milligram arm and 75% in the 900-milligram arm achieving virologic response compared to 0 in the delayed treatment arm. The primary composite endpoint was achieved in 45% and 35% of patients in the 300-milligram and 900-milligram arms, respectively, versus 0 in the delayed treatment arm. Importantly, we continue to see further reductions in ALT and hepatitis delta RNA beyond the 24-week time point. Brelovitug was well tolerated across dose groups with no treatment-related serious adverse events and very low rates of flu-like symptoms. Overall, these results reinforce a compelling profile for brelovitug as a potential well-tolerated convenient single-agent therapy for hepatitis delta and provide confidence as we look ahead to top line data from the Phase III AZURE-1 and AZURE-4 studies in the second half of this year. We look forward to presenting full results from the Phase IIb portion in a late-breaking poster presentation at EASL. With that, I'll turn it back over to Chris.

Thank you, Joanne. These results represent a major milestone for Mirum, advancing potential game-changing new medicines to patients. And stepping back, Mirum is entering a new phase of growth and value creation. We now have a high-performing commercial business that continues to generate strong and durable growth alongside 2 emerging therapies in adult liver disease, each with important upcoming milestones as we move towards potential registration. Looking ahead, our focus is clear. For brelovitug in hepatitis delta, we are on track with the AZURE-1 and AZURE-4 Phase III studies with top line data expected in the second half of 2026. For volixibat in PSC, our next step is this summer's pre-NDA meeting with the FDA as we prepare for a potential NDA submission in the second half of the year. And in parallel, we will continue to advance the VANTAGE study in PBC through its confirmatory stage with top line data now expected in the first quarter of next year. For the balance of the pipeline, the LIVMARLI EXPAND study is on track for top line data in Q4, and we expect top line data from MRM-3379 in Fragile X syndrome next year. Taken together, we see a clear opportunity to extend our leadership in rare disease, building on the same foundation that has driven our success to date. Once again, thank you to the patients and investigators who participated in VISTAS and AZURE-1 and a huge thank you to the Mirum team who are working tirelessly to make these major advances in research possible. And with that, operator, please open the line for questions.

[Operator Instructions] Your first question comes from the line of Ryan Deschner with Raymond James.

Congrats on the data set. What have you learned from the baseline characteristics of the enrolled population and the placebo response in this study with regards to patient heterogeneity and how chronic or intermittent pruritus can be in the PSC indication? And I have a follow-up.

Thanks for the question, Ryan. Yes, I mean first observation on that. I mean we've enrolled this study for pruritus, and so that shows up in the baseline criteria. And one of the things that I think worked very well in the study design and give credit to the team here at Mirum is how we -- you see a quite low placebo response on those pruritus values. And so not only does that point to good study conduct, but also shows that the concept that has been talked about of intermittent pruritus and PSC is not really something that showed up in these patients that placebo arm, you see persistent itch throughout the study, which is, I think, kind of a new finding for a study like this being the first time we've looked at pruritus in this amount of detail in PSC. And what was your follow-up?

Quick question on the pruritus signal seen in the mild pruritus patients, statistically significant, which is impressive to see. Can you remind us what range is considered mild -- and if you can, the mean baseline itch score for this mild group?

Yes. We're not discussing the specifics of that at this point. But just to kind of reassure you that we did measure it carefully and then sort of the patients kind of based on the severity of their itch at that point. But essentially, based on the 0 to 10 itch scale, there's kind of less room to move when you look at the mild pruritus. And I think that actually makes the results pretty satisfying for us in that group as well. So we certainly didn't expect to see that statistically significant response, but I think that just shows you how well volixibat works.

We'll look to have some of that data presented at one of the upcoming conferences. But the baseline was really just over 2, it's about 2.3. So to move -- have a significant move from that baseline was a great finding from the result.

Your next question comes from the line of Josh Schimmer with Cantor.

Congrats on another positive trial. Did you kind of look at the interim analysis of the VISTAS study and how that compared to the final results since there may be some relevant read-throughs to how we interpret the interim from the VANTAGE trial. And maybe you can talk a little bit about why the magnitude of separation in PSC may not be quite as large as you've seen in PBC.

Thanks for the questions. Yes, we did see -- as part of the unblinding, we did see the results from the interim portion. Overall, consistent profile. And what I'd say is the way we designed the study, having the data monitoring committee make the dose decision and viewing the results all generally consistent with the final results, I think we would have made the same decision if we had been unblinded. So overall, again, pleased with how the study design and conduct played out here. And then in terms of the magnitude of change, we powered the study on a 1.75 change versus placebo. So really saw that coming very much in line with that. And what played out differently from a statistical standpoint was the variability of the data was much lower, so a much tighter response range and placebo performance that we talked about before that ended up with a higher significance from a statistical standpoint.

And in terms of the underlying disease biology, any reason why one would be more responsive than the other?

Yes, Josh. I think that's a good question. I think we have to remember that PSC and PBC are really different diseases. I know we're doing studies of volixibat in both of them, we consider them under the umbrella of cholestatic pruritus. But if you think about just the course of disease and the origin, they are quite distinct. With PSC really showing a lot of fluctuation, both biochemically as well as just in the clinical course, patients with cholangitis that can occur. Some patients have multiple episodes. They may have biliary strictures, require intervention. And so that fluctuating disease course with kind of underlying progression is a bit different than kind of the slower kind of monotonic progression that you see in PBC. And I think we see that as well in terms of labs and also just the -- how these patients behave during the course of 6 months. So I think even though we have kind of lined them up side by side, and we're starting to look at that in 2 different studies, they are different disease entities. So I think it is difficult in different disease conditions. So to our view, I mean, this is really the only controlled study of itch in PSC that's out there. And I think the result is a robust...

Your next question comes from the line of Swayampakula Ramakanth from H.C. Wainwright.

Two quick questions from me. The first question is on the hepatic safety. Can you quantify the magnitude and reversibility of the ALT, AST and bilirubin elevations? Were there any cases of Hy's Law cases? And in terms of the discontinuations of 9.1%, can you help us understand what percent was LFT driven versus diarrhea driven? And the second question is on the breadth of the label. Obviously, the mild second cohort showed statistical significance, which is pretty good. Do you think you can get a label which covers all the way from mild to severe populations?

Yes. Thanks for the questions. I'll start with the label and then have Joanne comment on some of the safety profile questions. And overall, the labeling we've seen for IBAT as the class really just points towards pruritus being the indication cholestatic pruritus. So there's not really a concept of grading of severity. So that's kind of what we expect to play out here. I'd also say kind of on the labeling, this kind of [ reason for the ] safety profile here for what we see in this study. The results are pretty consistent across IBAT as well in terms of the liver safety and having monitoring labeling as part of the class. So expect that to be part of an eventual volixibat label as well. I'll have Joanne speak to the specifics.

Yes. Okay, thanks for the question. In terms of -- you asked about Hy's Law. I think you're aware that Hy's Law really was developed in the setting of having a normal liver. And obviously, these patients don't have a normal liver. And actually, we also know that PSC disease without volixibat or any other treatment by itself actually can be associated with fluctuations in some of the biochemical abnormalities that look just like DILI. So all of those things make it pretty difficult to kind of sort out all this. We're in the process of putting that together. We'll be reviewing it with some independent external folks to help us with that assessment. For today, I think really what's important to note is as you can see on the adverse event slide, I think, which is in Slide 10 of the deck, you can see some of those things reflected the underlying changes essentially in some of the what we viewed as clinically significant lab elevations like ALT, bilirubin.

And specific to your question on discontinuation, there was one patient who discontinued for lab elevations in the volixibat arm.

Your next question comes from the line of Gavin Clark-Gartner with Evercore ISI.

This is Yesha on for Gavin. I was wondering if you guys could speak to what you saw in the patient-reported outcomes, specifically around fatigue and sleep. Were you able to note directional improvements or nominal significance across any of the groups?

Yes, thanks for the question. We did see trends in fatigue and sleep in terms of improvements that favored volixibat. For fatigue, it was a trend and because of the way that we set up the hierarchical analysis, once we start missing something, then we're kind of technically not allowed to go further because the FDA kind of holds their feet to the fire for that. The nominal p-value for sleep was actually significant, however. So I think this actually all kind of hangs together. It makes sense. We've significantly improved itch, trend in fatigue, trend in sleep. These were -- the fatigue and sleep were included in the study to kind of give us some insight into that. But obviously, the study itself is not designed to look for those improvements. So I think the overall data really kind of hangs together for what we expect.

Your next question comes from the line of Mani Foroohar with Leerink Partners.

You have Ryan on for Mani. Congrats on the data. How should we think about the differences in baseline characteristics, whether that be gender or serum bile acids and how that may have impacted the results between the 2 arms? And then maybe just one commercial one. Can you guys just talk about your launch expectations given this is moving into an adult setting and based on our channel checks, pruritus is not active or proactively asked about by physicians. So maybe just some initial launch expectations as well as we look into next year.

Ryan, thanks for the question. So your question was about impact of gender differences and serum bile acid differences. I'm not sure that, that has a big impact really. There was fairly -- the gender balance is really equal among both sides. I think in terms of the group, 46% versus 61% being female. I don't think that's that big of a difference. The study results is strong. So I doubt that, that has any impact on it in terms of that. In terms of the serum bile acids, there is an imbalance at baseline. So the serum bile acids in the volixibat group is higher. However, both of those values are significantly higher than normal. So again, I think that reflects probably a few kind of outliers there. I'm not sure that we don't really read a whole lot into that. The study was not selected based -- patients were not selected based on serum bile acids. They were selected based on itch. And I think that's where we look to the interpretation is that we selected patients with pruritus and it demonstrated improvement in pruritus. So I think that's where we -- that's where our takeaway is. Obviously, we'll look more closely at bile acids and other [ provisions ] at some later point.

I'm going to ask Peter maybe to speak about the launch expectations.

Yes. Thanks for the question, Ryan. And I think it's an astute point. Certainly, if you do calls, you'll hear a wide range of clinical practices and estimates for pruritus, and it's not as front and center today as it should be perhaps because there are no approved therapies and nothing to offer these patients. So this will be our wood to chop as we move towards launch and not an unfamiliar exercise for Mirum. It's -- this is somewhat similar to what we had to do on the pediatric side over the last 5 years. And we will expand our team to have a larger footprint in adult care settings, but really excited about the opportunity to have the potential first approved therapy in the...

Your next question comes from the line of Joseph Thome with TD Cowen.

Congrats on the data. Maybe the first one, just a bit of bookkeeping. Can you comment if this is all you need from a safety database side of things for the NDA submission? Or do you need to follow these patients for any longer, and that might be gating to the H2 submission in any way? And can you comment a little bit in the real world, how often are these patients assessed for liver enzymes when they're seen with their physicians? And maybe last quick question. How do you think about any necessary changes to your sales force once hopefully that is approved and available to your team?

Thanks for the question, Joe. Yes, I'll start off, and then we'll pass it over to Joanne on monitoring and Peter on the commercial team. This overall on the expectations for the NDA submission, we do see this as everything we need from a clinical standpoint for the NDA. Given the size of PSC as an indication, this is a substantial safety database. And just as a reminder that this -- the conversation and expectation with FDA is that this will be submitted for a full approval with pruritus being the outcome for the basis of that approval and looking forward to discussing all that with FDA this summer. And then maybe Joanne can speak about kind of standard of care monitoring in PSC.

Yes. So these patients, because of their risks and just their clinical course are seen fairly frequently. I mean, the risk of cholangiocarcinoma is actually quite high. So I believe the AASLD recommendations that they're essentially monitored every 6 months or so. If they have cirrhosis, they're also monitored for hepatocellular carcinoma. And then as well, many of them have -- might have episodes of acute cholangitis, which bring them in as well, and they may need procedures for that. So this is a fairly closely monitored population just because of the complication rate of their underlying disease.

And in terms of our field force sizing, yes, as mentioned before, we will be expanding just to use the U.S. as a frame of reference. I mean, today, we have about 15 folks on the sales side doing the liver side of things, which gives us a strong presence across the board in pediatric care delivery settings as well as, I would say, the top decile, the biggest centers on the adult side, where we're finding adult PFIC patients. We'll expand into probably somewhere in the 60s total on the liver side. That will actually use that team to promote brelovitug, if approved, for hepatitis delta. That will allow us to get into the full kind of setting where PSC patients are taken care of and also hopefully find more adult PFIC patients out there.

Your next question comes from the line of Jessica Fye with JPMorgan.

I had a couple on volixibat and then one on brelovitug. On volixibat, do you expect that the 56% versus 26% 2-point responder secondary endpoint data could get on the label? Second, on volixibat, it's between the -- I think it was north of a 2-point placebo-adjusted benefit you saw at the interim in pruritus with PBC and the 1.64 point delta you saw today in PSC. Can you talk about your confidence in being able to deliver data in pruritus with PBC that would compare well to volixibat? And then on brelovitug, with the 300 weekly and 900 Q4-week data looking directionally different from the prior data, acknowledging the different time points? Is it your expectation right now that you'll likely file for both the 300 weekly and 900 monthly dosing regimen?

Thanks for the question, Jess. Yes, I'll touch on some of those. First on the label and what we'll be proposing for volixibat, again, the indication statement that we're proposing we expect to have is treatment of cholestatic pruritus in PSC. And then in the clinical trial description, there will be some discussion of the efficacy data. So ultimately, at this point, unclear whether that response rate is one of the specific data points that's in there. So a little early to be able to speak to specifically what would be -- what we think will end up in there. And then speaking on PBC confidence, given what we saw in the VANTAGE interim, what we're seeing here, I think we're in really good shape heading into the full analysis for the VANTAGE study. If this is -- we're seeing now consistently with volixibat, really strong placebo-adjusted difference here. And in particular, with the PSC results, the VISTAS results, just as basically the ratio of placebo change to drug is really remarkable. And so I think that speaks quite a bit for the VANTAGE study as well in the first quarter of next year. Then kind of moving down to brelovitug, maybe you can have Joanne comment a little bit on the findings. But ultimately, in the Phase III study, both doses are in there in the final analysis, and we'll be able to make that determination when we have the data in terms of the filing package. But I'll let Joanne speak to kind of what we observed from those 2 dose levels.

Yes. Jess, thanks for the question. You're correct that directionally, they were a little bit different. But I think we're -- we have to remind ourselves that the data set is fairly small. And so we are running the Phase III studies for the Phase III for AZURE-1 and as well AZURE-4, and we'll make a final determination at the end of the year when we unbind those. I think it's -- we're hesitating for making too big conclusions based on the limited data set. Directionally, we feel confident in the results. So we're sticking with that, and we think this is actually overall, very consistent with prior Phase II data that we presented. No major differences there.

Your next question comes from the line of Mike Ulz with Morgan Stanley.

Congratulations on the data as well. Maybe just a follow-up on the significant benefit you saw in the mild patients, which I think was a bit of a positive surprise for us. I guess does that change your view on the potential market opportunity for volixibat? And then I have a follow-up. Thanks, Mike.

Yes, I mean, it certainly is nice to have that data. And our message with LIVMARLI has always been any level of pruritus is a signal and it deserves to be treated and to have that data in hand, I think will be kind of helpful for the launch effort. I don't know if it fundamentally transforms. I mean these are scales used in clinical trials in the real-world setting, it's unusual for someone to rigorously measure itch the way it's done in clinical trials. And I think what we've seen with LIVMARLI is that those patients do come to therapy, and we'd expect a meaningful proportion to do the same.

Got it. And then just for the upcoming pre-NDA meeting scheduled for this summer, anything specific you're looking to get clarity on from the FDA? Or what's going to be the focus there for you guys?

We see that as a pretty routine presubmission meeting just to align on a format of analyses and data sets. In terms of what's in the package overall, we've had good communication throughout the history of the PSC program and also as part of the post -- the PBC breakthrough designation conversation. We've been able to get good feedback and clarity along the way. So don't feel that there's really much to be debated, so to speak. It's really just the standard presubmission meeting.

Your next question comes from the line of James Condulis with Stifel.

Congrats on the data. Just wondering what we can expect at EASL in May in terms of like additional data? Is that where we may see things like fatigue and sleep? And then maybe one more sort of follow-up on the commercial side of things and totally understand it's way too early to be any sort of getting into specifics, but just curious if there are good analogs to look at here as it relates to things like pruritus and the launch as we approach a potential launch here.

Thanks. On EASL, a little early to comment on what specifically will be presented. Excited that EASL recognizes the importance of this data set and that we're having one of the headline late-breaker oral presentations, but we do plan to get deeper into some of the analyses in that presentation. And maybe I'll ask Peter to speak to the commercial analogs.

Yes. I think probably the best analog we can think of is right here at home at Mirum, LIVMARLI and Alagille syndrome, well-diagnosed disease, perception amongst providers of a variable pruritus phenotype. We're almost 5 years in from our first launch in the U.S. there, and we've talked about how we reached about a 50% penetration, but we continue to add patients every month, every quarter and have kind of clear line of sight to that being kind of the continuous adoption dynamic for the life cycle of the product. And as best we know, that's probably a pretty reasonable way to think about how a launch adoption curve looks in PSC.

Your next question comes from the line of Jonathan Wolleben with Citizens.

Just a couple for me. When you guys talk about the commercial opportunity in your slides, you mentioned that median worst itch score is typically around 8 and baseline here is more around the 6 level. So wondering if you captured the patients you wanted to in this primary group or if there's any difference in the population here than you would have expected?

Thanks for the question, Jon. Overall, I mean, this -- we see the VISTAS population is really representative of what PSC looks like out there, both in terms of the pruritus burden and what we see over time, kind of what we spoke to with the persistent itch on the placebo arm, the rough proportion on how people are scoring their itch between the moderate to severe and the milder patients. And then also just the underlying kind of complications that happen in PSC patients that we saw throughout the study, just that it's a really tough disease. So I do think we have a very representative population in the VISTAS study.

Okay. And then the diarrhea, it actually was a little bit better than we would have expected based on the VANTAGE interim. But I wonder if you could talk a little bit about categorization, temporal pattern and then if there was any difference in the IBD population as well.

Yes. Thanks for the question. So the diarrhea was all grade 1 or grade 2. So no grade 3 diarrhea in the double-blind portion. In terms of kind of onset, onset median within the first couple of weeks of starting therapy. And then duration in terms of the median is about a couple of weeks as well. So in most patients, not prolonged. We looked carefully to see if giving an IBAT with a known characterized adverse event of diarrhea could trigger exacerbations, and we don't see any evidence of that. There was a pretty careful look in patients with IBD if they develop diarrhea, so we collected fecal calprotectin to see if we could see evidence of increased inflammation, look carefully for C. Diff and all of those other kind of causes. Currently, we don't have any evidence that giving an IBAT to these patients actually increased IBD exacerbation. So I think that's actually very reassuring for us and also for patients as well.

Your next question comes from the line of Lisa Walter with RBC.

Congrats on the results today. Just 2 for me. Did the 80% of patients on UDCA background therapy have a greater improvement with volixibat added on versus those on monotherapy? And during your pre-NDA meeting with the FDA, do you plan to discuss potential for priority review for volixibat? Any color here would be helpful.

Thanks for the questions, Lisa. Yes, starting with the FDA conversation, we will propose priority review. I think this setting has a tremendous unmet need and really fits the profile for priority review. So that will be part of the conversation. Then kind of on UDCA response, initial look, we're not seeing really any difference in response across different criteria, but still early in cutting the data, but nothing really to speak to out of the top line results.

There are no further questions at this time. I will now turn the call back to Chris Peetz for closing remarks.

Great. Well, thanks, everybody, for joining the call this morning. Really excited about bringing volixibat forward for PSC patients, and we also look forward to providing our Q1 update later this week.

This concludes today's call. Thank you for attending. You may now disconnect.