Mirum Pharmaceuticals, Inc. (MIRM) Earnings Call Transcript & Summary

Welcome to the Mirum Business Update Call. My name is Carla and I will be coordinating your call today. [Operator Instructions] I would now like to hand you over to your host, Andrew McKibben, VP of Finance and Investor Relations, to begin. Andrew, please go ahead.

Thank you, Carla. Good day, everyone and welcome to Mirum's conference call to discuss the results of the interim analysis of our VISTAS PSC and VANTAGE PBC Phase IIb studies of volixibat. I'm joined today by our CEO, Chris Peetz, our Chief Medical Officer, Joanne Quan; and our Chief Financial Officer, Eric Bjerkholt. The call will begin with opening remarks from Chris, before turning it over to Joanne to walk us through the results. After the prepared remarks, the presenters will be joined by Eric for the Q&A session. Earlier today, Mirum issued a news release announcing the results of these interim analyses. A portion of the news release issued today can be found in the 8-K filed with the Securities and Exchange Commission this morning. This news release and a copy of the slides that we will be referencing today can be found in the Investors section of our website. Before we start, I'd like to remind you that during the course of this conference call, we'll 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. These statements represent our judgment 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-Q and subsequent SEC filings for more information. And with that, I'd like to turn the call over to Chris. Chris?

Thanks, Andrew. This is an exciting day. On behalf of everyone at Mirum , I'm honored to announce the positive results of our interim analyses for both our VISTAS PSC and VANTAGE PBC Phase IIb studies of volixibat . Now across multiple settings of cholestasis, we have demonstrated the potential that IBAT inhibition has to rapidly and significantly impact burden of disease. This is another significant step on Mirum's journey and commitment to bring effective treatment options to patients living with rare disease. I'm proud of the great strides Mirum continues to make for our patient communities. To name a few, we have built an industry-leading rare disease team with the expertise to bring medicines from concept to global reach. We achieved the approval and growing global adoption of LIVMARLI for Alagille syndrome. And we just celebrated the recent expansion of LIVMARLI's label in the U.S. for treatment of PRURITUS DUE TO PFIC and a positive CHMP opinion in Europe for treatment of PFIC. We seamlessly integrated CHOLBAM and CHENODAL into Mirum's portfolio, 2 standard of care medicines for high-need genetic disease settings. And now today, we've completed an important validation of the potential for volixibat to become an important treatment option for cholestatic pruritus. Now a bit on the interim results. Starting with the VANTAGE study in PBC, the statistically significant primary endpoint of a 2.3 point placebo-adjusted change in pruritus exceeded our hopes for the interim results and charts a clear path forward to advance the study at the 20-milligram dose. This is a substantial opportunity for Mirum, with an estimated over 230,000 PBC patients in the U.S. and Europe, 60% of whom experience pruritus. Turning to PSC. We are encouraged that the VISTAS study exceeded the prespecified threshold for continuation. The advancement of volixibat is particularly meaningful for PSC patients who have no approved therapies. There are approximately 54,000 patients across the U.S. and Europe with PSC and about 2/3 of them suffer from pruritus. The volixibat program now moves towards -- into an important expansion step to confirm the observations from the interim analyses. We have incorporated regulatory feedback into these studies and believe that if the results are confirmed in the final analysis, each has the potential to support an NDA and bring volixibat to patients. And with that, I'm now happy to turn the call over to Joanne to discuss the results of both studies in more detail. Joanne?

Thank you, Chris. I'm pleased to be with you today to share the outcomes of both our VISTAS and VANTAGE studies. To start, I would like to express my gratitude to our investigators, trial participants and their families for their support of this important research and our efforts to improve patient care in these adult settings of cholestasis. I'll begin with the VISTAS study in PSC. As a reminder of the trial design, this is a 28-week, double-blind, placebo-controlled seamless adaptive study. The interim analysis consisted of 3 arms and patients were randomized to receive either 20 milligrams of volixibat, 80 milligrams of volixibat or placebo. The interim analysis [indiscernible] more than 42 subjects completed at week 16 visit. The study remains blinded and we are very happy to say that the data review committee has recommended continuing the study on a blinded basis of the 20-milligram BID dose. This signifies that the selected dose surpassed our prespecified minimum criteria for efficacy and safety. Given the results today, we expect to complete enrollment for this study in the second half of 2025. Turning to the VANTAGE study in PBC. The study design mirrors our VISTAS study with the exception of an open interim analysis, whose results, I'm pleased to share with you. The interim analysis included 30 subjects randomized evenly across 3 arms, again, 20 milligram volixibat, 80 milligram volixibat and placebo at sites in the U.S. and Europe. Baseline demographics and patient characteristics were well balanced across study arms with a mean baseline itch score of 6.5 out of 10 indicating the severity of itch in this patient population. Baseline serum bile acids and liver function tests were characteristically elevated and comparable across study arms. Overall, 95% of patients were receiving UDCA at baseline. Approximately 2/3 of patients in the study had baseline alkaline phosphatase levels below 1.67x, below normal, confirming the burden of pruritus across all settings of PBC. The primary endpoint assessed the mean change in the adult ItchRO score, from baseline compared to the average Itch score of weeks 17 to 28 of the study using mixed effects model with repeated measures analysis. As a reminder, the adult ItchRO is a 0 to 10 worst-itch numerical rating scale completed once daily. I'm very pleased to say that both doses of volixibat demonstrated large and statistically significant reductions in itch. Specifically in the volixibat treatment arms, we saw a 3.8 point reduction in the itch score. These reductions for the volixibat arms correspond to a 2.3 point improvement over placebo, highly statistically significant with a p-value of 0.0026, which we believe is an outstanding treatment set. Reductions in serum bile acids and improvements in multiple dimensions of the PBC-40, particularly fatigue, were also observed. The clinical and statistical magnitude of these interim results underscore volixibat's potential and validate our approach to optimizing dosing from IBAT inhibition in settings of [indiscernible] spaces. Overall, we are very encouraged by the pruritus response and clarity of the effect, coupled with a statistically significant improvement in fatigue at week 16. Safety and tolerability were also comparable between the 2 doses with the most common event being treatment-emergent diarrhea as expected, which occurred in 77% of patients in the volixibat arms. Diarrhea was mild to moderate and most was transient. 1 volixibat patient discontinued due to diarrhea. There were 4 patients with serious treatment-emergent adverse events, including 1 in placebo, with clinically relevant changes in liver enzyme [indiscernible]. Given the comparable efficacy and safety profiles of the 20-milligram and 80-milligram treatment arms, the VANTAGE study will proceed with the same 20-milligram BID dose that will be moving forward in the VISTAS PSC study. For the final analysis of VANTAGE, we expect to enroll up to an additional 200 patients. We've built strong momentum going into the confirmatory portion of the study and we'll be expanding to a total of approximately 100 sites in 14 countries by the end of the year. We expect to complete enrollment in 2026. Overall, we're extremely excited by the strength of these results and the implications for future treatment in PSC and PBC. Now I'd like to turn it back over to Chris.

Thanks, Joanne. This is a great day for patients with PSC and PBC. The results today support volixibat's potential to address the burden of cholestasis in these settings. I would like to reiterate our thanks and appreciation to the PSC and PBC patient and investigator communities around the world for their support of our efforts. These results would not have been possible without their close collaboration. We will work with urgency to advance both of these studies to final data and are energized by yet another opportunity to bring an important new medicine to patients in need. These interim analyses built on several additional milestones throughout the remainder of 2024 for Mirum, -- for LIVMARLI, our sNDA to lower the approved age for the treatment of cholestatic pruritus and PFIC in the U.S. is under review and we anticipate a label update later this year. In the EU, we expect approval for treatment of PFIC in the third quarter for LIVMARLI. In addition, our NDA for chenodiol and CTX is on track to be filed later this month. In summary, we are continuing to execute well on our mission to make Mirum a leader in providing life-changing medicines for patients with rare disease and look forward to providing additional updates throughout the year. And with that, we'll open the line for questions. Operator?

[Operator Instructions] And now our first question comes from Jessica Fye from JPMorgan.

Great. On the baseline ItchRO scores, curious if you think the modest differences across the arms factored into the efficacy or kind of how you interpret these efficacy results in PBC? And second question is, curious if you saw any improvements in alkaline phosphatase, any other kind of liver markers apart from serum bile acids?

Thanks, Jess, for the question. I'll turn to Joanne.

Yes. So the baseline Itch was pretty comparable in all of the arms and we had a substantial treatment effect associated with both volixibat treatment arms. So we don't think that there's, #1, a whole lot of difference in terms of the baseline itch across the arms nor do we think there's an effect in terms of the overall response in itch. With respect to your question about liver chemistries, we do not see changes in this dataset within [indiscernible].

On the liver chemistry front, it's also important to keep in mind that this population, I think it is mostly a first-line setting population of patients, 2/3 of them, as Joanne mentioned had alkaline phosphatase levels below 1.67x the upper limit of normal. So a lot of these patients had normal levels coming in. So we wouldn't expect to see an improvement on normal.

Got it. And just as a follow-up, can you speak to what the background meds looked like more broadly, for example, what proportion of patients were on background fibrates?

Yes. So we had a handful of patients on background fibrates. We had practically all of the patients, 95% of them or more on UDCA as one would expect in this population. And just under 70% were taking systemic antipyretics. So clearly, population, which is suffering from pruritus is looking for answers here.

Our next question comes from Josh Schimmer from Cantor.

Congrats on the results. Maybe first a quick follow-up to Jessica's question. Would you expect to see improvement in those patients who did have ALT elevated at baseline? And was there any indication you were seeing that?

So we did not see a change here. In terms of looking at IBATs, they've not tended to show changes, simply within this liver parameter in the past. So we continue to look at the data as it matures. And then ultimately, the final dataset, we'll also be looking at things like Fibro Scan, other fibrosis markers, I think will be an interesting [indiscernible].

I think also just to add on how we're looking at endpoints kind of strategically with the volixibat program by focusing on pruritus, which is -- obviously, it's a day-to-day outcome that's very impactful for patients. That gives us a registrational endpoint that can apply across all settings of -- for PBC patients. It allows us to bring a treatment option for not only those with elevated alkaline phosphatase but those with normal levels.

You also indicated 4 patients experienced SAEs, including 1 in the placebo arm. Can you provide additional details on what those were?

Yes. So reviewing these. For instance, we had a patient who -- with a history on immune disorder, we had a [ suicide ] attempt in the study, a patient -- the same patient actually had a history of [indiscernible] -- episode of syncope in the study, small bowel obstruction in a placebo patient and then, for instance, an incidence of [Audio Gap] of liver injury [indiscernible] so that was during the [indiscernible] portion.

Got it. And then there were high rates of diarrhea as noted. Do you have a split in terms of what percent and roughly what percent was mild versus moderate and how long did it persist? Or in what percent of patients did it not resolve?

Yes. So most were transient. When we looked at the top line data within the first 1 or 2 weeks, which is pretty typical of what we've seen with [indiscernible] in our experience in the past. We've allowed symptomatic therapies. So patients -- maybe half the patients, it looks like, took the symptomatic therapy, the others half did not. And so they were mild, were moderate and they were not severe [indiscernible].

I think one other, on kind of persistence. One other really encouraging observation is when we look at the patients that have made it to completion of the double-blind portion, nearly all of them opt to continuance of the long-term extension. We see really good persistence in that open-label extension after the randomized period. So clearly showing a well-tolerated profile and the benefit of being on therapy.

And then a last question for me. To what do you attribute the improvement in fatigue that you're seeing in these patients?

That's a good question. It's quite striking, especially at this point, in looking at the data. We're not sure. We do have to do a more complete assessment in terms of quality of life measures that we'll be getting at the end and that should give us some better insight into this.

Our next question comes from Mani Foroohar from Leerink Partners.

You have Ryan on for Mani. Just a quick one. Did you guys see any correlation or differences in pruritus reduction based on the baseline alk phos levels? I know it's kind of a small [ n ] at this point but just wondering if you can shed any light on that.

Yes. Thanks for the question. Obviously, small data sets and we're looking at top line data. Nothing obvious pops out in terms of that question. But as we get more data and data set matures, we'll obviously be looking at things like this.

Great. And then 1 additional one from us. You guys said that pruritus reduction was observed as early as week 1 but can you provide any light as to the average time it takes for a patient to reach pruritus reduction?

So if we look at the time course, it starts to decrease within the first week and so I think that's quite striking and I think that's quite a big benefit that we can document for patients. We haven't actually teased out time to maximum response just yet in this dataset.

Our next question comes from Gavin Clark-Gartner from Evercore ISI.

Let me add my congrats on the data also. Just first, based on your market research, roughly what percent of PBC patients have lower ALP scores and also moderate to severe pruritus?

Thanks for the question, Gavin. It's really striking, is that the population we see in our study is really consistent with what we saw from the market research. So we do expect to see a similar proportion on baseline liver biochemistry in the general population. And to drill down a little bit more, it's -- roughly 1/3 of patients have -- are expected to have a normal alkaline phosphatase. 1/3 are in the kind of normal to 1.67x upper limit of normal and then 1/3 being a more traditional second-line patient with above 1.67x above normal. And that's exactly what we have in this data set, in this 1/3 niche category.

That makes sense. Maybe you could just compare and contrast how this compares to what we've seen with linerixibat previously?

Yes, the -- I think overall, what we can say in kind of the broader picture is that the profile for volixibat looks like an IBAT. You see clear reductions in bile acids, that rapid improvement in pruritus and typically transient treatment onset diarrhea that is mechanistic, that's part of how the drug is clearing bile acids. What we see for the volixibat program, in particular, in how we've achieved this really strong result compared to precedent data is all in our view in how we've approached dosing and to make sure we've done prior to the study, did quite extensive dose-ranging work going in expecting that the 20-milligram dose would be highly active and had the 80-milligram dose just to make sure we weren't leaving any efficacy on the table. That's exactly how it's played out. And from the -- our view of the literature, this is the -- this is a really strong result when you look at some of the precedent data.

Our next question comes from Dae Gon Ha from Stifel.

This is [indiscernible] on for Dae Gon. Basically, 2 from us. Based on your FDA discussions, how confident are you that the planned enrollment sizes for both the VISTAS and VANTAGE are sufficient to provide a safety database? And then also from a -- given the [indiscernible] precedent, can you confirm that none of your volixibat preclinical studies uncovered any AEs on fetal and newborn development?

Thanks for the questions. I'll give a perspective on the FDA interactions and ask Joanne to speak to the nonclinical package. But overall, for our pre-IND correspondence with FDA, we've got a really clear direction on what the expectation was for safety database size and use of pruritus as an endpoint for a full approval. And that's a important -- just a reminder here is that these studies are oriented towards full approval rather than an accelerated approval. And it was quite clear and it allows us to size these studies for what FDA asked for in terms of safety database. That's what we're doing. So feel great about the program moving forward.

And in terms of the nonclinical, I mean, this has a very clean nonclinical package. You recall that IBAT inhibitors, including volixibat, are largely -- stay within the gut. So they don't provide much systemic exposure at all. So I think that gives an additional measure of safety in thinking about this patient population.

The next question comes from Steven Seedhouse from Raymond James.

Chris, in your opening comments, you mentioned 60% of PSC patients having pruritus. I assume that includes mild pruritus but I just wanted to double check. Is that moderate to severe? Or is that all pruritus?

Yes. Steve, thanks for the question. Yes, to clarify, that's all pruritus. So you do expect to see a range there. But 1 kind of observation I'd add on top of that, in particular, we see from our experience in launching LIVMARLI in the pediatric setting is that before a real effective therapy is available, there's not adequate discussion and discovery of pruritus in patients in these settings. So we do feel that, that could very well be an understatement. And as physicians actually start to engage their patients, they'll -- as they have a treatment option, you tend to really understand that there's more burden there and a lot of patients tend to normalize it because they don't have anything else to do other than find out how to live with it and cope with it.

Okay. Makes sense. Two clarifications on the data. Just on the -- first on the fatigue result at week 16. Was that persistent at 6 months? And then on the SAEs, just wanted to clarify, if any of those were deemed treatment related, particularly the liver injury SAE that you noted earlier?

Yes. Thanks for the question. And just I'll hand it over to Joanne. But in terms of the timing of these interims, keep in mind, they were triggered when the final patient for the PSC interim analysis crossed the week 16 portion. So that kind of informs where some of these analyses were run. I'll call Joanne to speak.

Yes. So in terms of the fatigue, we only have that week 16 result currently. Obviously, we'll be looking very closely at the follow-on data with great interest. With regard to the SAEs, the ones I mentioned occurred in the double-blind period. We had 1 patient who had an episode of colitis, who had been treated at that point for about 1 year with study drug who was in the hospital for a few days to get [indiscernible]. And so the investigator deemed that's related, however, looking at the overall case and looking at the safety data in the aggregate, we felt it was not, at least, concern to us. So we thought the overall safety database, our assessment of the safety data is not different to the early safety signals here.

The next question comes from David Lebowitz from Citi.

First on PBC. Could you, I guess, elaborate on how you think this volixibat might fit in the treatment paradigm in comparison to maralixibat and seladelpar, given the datasets we've seen to this point?

Yes. Thanks, David, for the question. In general, this coming back to the broad population that we have here, that's a key element and seeing how volixibat can fit into the treatment paradigm here. We -- given that we have no baseline alkaline phosphatase criteria, these patients, as we mentioned, really cover both the first and second-line setting. So really broadens the eligibility and the eventual expected label in terms of at what stage of disease that the patients are in. So it allows volixibat -- it has an opportunity to potentially be used before a PPAR fibrate therapy or OCA, for example but then also, we are gathering and evaluating patients in that second-line setting as well. So there were a few patients on background based on fibrates in this data set, for example, that did not have their pruritus controlled and saw a nice response. So I do think that there's a role that we'll expect to play across all settings. And then in terms of kind of how we position it against -- with the potential linerixibat data upcoming, because we think we optimally approach dosing here. And that's led to this quite strong treatment effect. So our goal is to have a highly effective treatment option for all patients with pruritus and PBC.

In terms of the fatigue, is there any correlation between introduction and sleep that might play a role in the fatigue?

Yes. Thanks for the question, David. It's a good thought and that's one of the questions in our mind as well. We don't -- we have some additional data that will be coming, ultimately the final dataset, which should help us achieve that, that relationship of ours. Right now, we just have top line and we see this striking effect on itch and effect in the PBC-40 [indiscernible]. We think this is particularly important for patients to know because, obviously, patients [indiscernible] 2 of the most [indiscernible].

And David, 1 actually really nice thing about this dataset that makes a correlation like that difficult is nearly all patients responded on pruritus. So it's really broad and inclusive treatment response profile that we're seeing.

Good to hear. And just lastly on PSC, given no approved drugs and pruritus certainly would seem like a reasonable endpoint, I guess to what extent have the discussions been with the agency on that as an endpoint? And would you say that they're very likely to accept it?

Yes. Thanks for the follow-up. Absolutely, the discussion has been very clear on endpoints across the program, both in the pediatric setting, in Alagille and PFIC, where we use pruritus as an outcome for approval. FDA has also said that would be a potential endpoint to support an NDA for PSC or PBC as well.

The next question comes from Jon Wolleben from Citizen JMP.

On PBC, can you talk a little bit about the clinical significance of dropping below moderate to severe pruritus for patients and how that could be differentiated? And then just a quick one on PSC. Any SAEs uncovered in the blinded interim?

Right. So just in terms of -- thanks for the question. So first, in terms of the significance of the itch. Clearly, this is a patient population that is looking for solutions for itch. We have nearly 70% of them who were taking systemic antipyretics. And we know from talking with physicians and patients as well that a number of them sort of try a number of different options, none of which have impacted. So we think that the response that we've seen is actually particularly meaningful to this patient population. And sorry, in terms of your second question, it was regarding SAEs. Is that correct?

Any SAEs in the blinded interim in PSC?

Let's see. So we do have ongoing safety monitoring there. Our data review committee reviewed safety as well as efficacy and did not recommend any changes to the study design. So they have been looking carefully at the safety, which we do monitor in real time, so nothing of concern there [indiscernible].

The next question comes from Brian Skorney from Baird.

Maybe as a follow-up to Steve's question on sort of difference in burden between PSC and PBC, was the baseline ItchRO score requirement the same for VANTAGE and VISTAS? And can you talk at all about the relative screen fail rates for each indication based on that score?

Yes. Thanks for the question, Brian. So we did include for both studies -- we're looking at moderate to severe pruritus. So that was similar in both studies. In terms of screen fails, that has actually improved quite a bit over time. And some of that is just, however, the sites have gotten better in terms of selecting patients and the ability to know how to ask about itch. We do know that both patients and physicians tend to kind of minimize and normalize it. So we actually provided some training for sites in terms of how to discuss the symptom with their patients and really encourage the patients who kind of come forward with what is bothering them and what is preventing them from sleep and their daily activities. So with that, we've actually found a bit more success in terms of including the appropriate patients. And also, we find the sites who routinely ask patients about their symptoms and actually have done quite well in terms of including the symptoms.

And Brian, just to add a little bit more on what does cause the screen fails and we have one in pruritus -- baseline pruritus will sometimes be the screen fail issue. But just a common or even more frequent is the baseline bilirubin levels might be above the starting criteria or often these patients have had other prior procedures that might make them ineligible. So we see that as frequently as the baseline pruritus.

The next question comes from Mike Ulz from Morgan Stanley.

Congrats as well. Maybe just 1 quick one. PSC. Can you just remind us what the threshold was on the interim pruritus analysis? And then maybe secondly, just PBC. You talked about the potential for a much broader market opportunity than some of the competitors, both in the front and second line setting. So maybe if you could give us just a breakdown between frontline and second-line patients there?

Yes. Thanks, Mike, for the question. I'll cover the second one first and then pass it to Joanne to talk about the interim criteria. In terms of mapping out the market for PBC, so there's -- we estimate about 230,000 patients and this is looking at U.S. and Europe broadly. Of those, about 60% will have pruritus. And that pruritus burden from all of our work is present at an equal rate in both the first-line, early-stage patients who'd be on just a background UDCA and have their controlled alkaline phosphatase level, the pruritus burden is similar in the more advanced second-line patient who might have elevated off [indiscernible] and be on fibrate. So we do think it's just a very simple -- take the 230,000 patients and 60% of them would be a target treatment candidate for volixibat, given this data. Joanne will speak to the interim criterion.

Yes. So the way the interim was set up for the PSC was quite similar to how we set up the PBC. And what the key difference is that we do not look at the data. So we don't have visibility to the PBC data. Again, we're looking at moderate to severe itch at baseline. And the way that we set this up was so that a independent data [indiscernible] would look at it and we set up a predefined efficacy threshold as well as how to look at that safety. So we know by then recommending moving forward that we surpassed the efficacy threshold and that we are satisfactory [indiscernible].

And one of the things that we've mentioned in our prior calls, as well as the [ powering ] assumptions for 1.75 placebo-adjusted effect and so that -- those criteria were to give us confidence that we've hit that in the full dataset. And what we see from the PBC results, obviously, makes us really excited about what's likely happening in that PSC dataset, showing a 2.3 placebo-adjusted effect is really encouraging for the VISTAS study.

And our final question comes from Ed Arce from H.C. Wainwright.

Congrats on the impressive data and this is Thomas Yip, asking a couple of questions for Ed. So first question, perhaps can you provide a breakdown of the PBC patients who experienced diarrhea between the 20-milligram and 80-milligram cohort.

Sure. Thanks for the question. Roughly similar proportions of patients reported diarrhea between those 2 cohorts. So the average number we gave was 77%, quite similar percentages. So similar to other IBAT studies and the diarrhea is not dose related [indiscernible].

Okay. Okay. Got it. And then perhaps if you can discuss what are some potential mechanism for this big improvement in these PBC patients in a very short given time frame?

Well, we know that IBATs work by decreasing serum bile acids because they increase the fecal excretion of them. And so we think that's the way that this is working similar to the IBATs working and other of the core set of conditions that we see that by taking the IBATs, you are essentially increasing your fecal bile acid excretion, you're decreasing your systemic exposure to it. And therefore, this translates to an improvement in pruritus.

And I think just to, Thomas, to really kind of going back to one of the prior questions, where you still have the mechanism for fatigue, there's a lot to learn there. We're not quite sure. One obvious thing to think about is, if you're not itching, you're likely able to sleep better than -- I think that's a big component of the fatigue but there may be more to the -- that systemic bile load that Joanne is talking about, you reduce the systemic bile exposure and there is some other mechanism of fatigue that is at play here. And we just don't know that yet.

Got it. Understood. And perhaps 1 final question for the VISTAS PSC study. So regarding the efficacy threshold, is this based on a specific figure or rather a trend of improvement in this measurement?

Thanks for the follow-up there. I mean the analysis and threshold is a statistical effect size. So it looks at the separation from placebo and the variability of the data for a time point and a view of the ultimate final end point. So it's looking at the MMRM of pruritus in the months 4, 5, 6 of the randomized period.

We currently have no further questions. So I'll be handing back over to Chris Peetz, the CEO, for final remarks.

Thank you, operator and thanks to everyone for joining the call. Look forward to our next update as we continue to execute across the programs. Have a great day.

And that concludes the conference call. Thank you for joining. You may now disconnect your lines.