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spk02: Hello everyone and welcome to the Miriam Pharmaceuticals third quarter business update conference call. My name is Victoria and I'll be coordinating your call today. If you would like to ask a question during the presentation, you may do so by pressing star followed by one in your telephone keypads. If you have joined us online, please press the red flag icon. I'll now hand over to your host, Ian Clements, Chief Financial Officer. Ian, please go ahead.
spk00: Thank you, Joy, and good afternoon everyone. I'd like to welcome you to Miriam Pharmaceuticals' third quarter 2021 conference call. I'm joined today by our President and CEO, Chris Peets, Pam Vig, Head of Research and Development, and Peter Radulich, Chief Operating Officer. Earlier this afternoon, Miriam issued a news release announcing the company's results for the quarter ended September 30, 2021. Copies of this news release and SEC filings can be found in the Investors section of our website. Before we begin, I'd like to remind you that during the course of this conference call, we will be making certain forward-looking statements about Miriam and our programs based on management's current expectations, including statements regarding Miriam's business plans, commercial and development programs, strategies, prospects, market opportunities, and financial forecasts and guidance. These statements are subject to numerous risks and uncertainties, and actual results could differ materially from the results anticipated by these statements. Investors should read the risk factors set forth in Miriam's 10Q for the quarter ended September 30, 2021, and any subsequent reports filed with the SEC. With that said, I'd like to turn the call over to Chris Beats. Chris?
spk07: Thank you, Ian, and good afternoon to everyone joining us on the call today. The third quarter was an exceptional period for Mirum, marked by the FDA approval of Liz Marley for cholestatic pruritus in patients one year and older with allogeal syndrome. The first ever approved medicine in this indication and the first FDA approved product for Mirum. Liz Marley's launch is a tremendous achievement and I'm very proud of our team for the impressive strides made this quarter. We are all humbled and excited about what it means for the allogeal syndrome community And I would like to again extend my thanks and appreciation to the patients, parents, caregivers, investigators, advocates, and employees that got it done. The hard work of the Merum team is delivering results. Our pre-launch preparations have resulted in a strong start in market. Today, Peter will speak to our commercial efforts, including an update on the many partner companies multiplying our efforts to launch Live Marley around the world. This quarter also witnessed several important milestones from our clinical and regulatory efforts. We submitted our application for Live Marley in Europe for the treatment of cholestatic liver disease in patients with algeol syndrome. And just today at the AASLD liver meeting, the Global Algeol Alliance presented landmark data that was part of that submission. These data showed a highly significant improvement in transplant-free survival for patients in Liv-Marley studies compared to a similar untreated group. Overall, a 70% risk reduction was seen. This presentation was the lead oral late-breaking presentation today and received best of liver reading recognition. We believe these results are nothing short of remarkable. Before turning the call over to Peter, I'd like to share a couple of updates on the leadership team. First, I'd like to thank Dr. Ed Tucker, who has served as Miriam's CMO since 2019, supporting the application and approval of Liv Marling, who is leaving the company. We wish him the best of luck as he embarks now on his next professional endeavor. Second, I'm excited to share that our Chief Scientific Officer, Dr. Pam Vig, is being promoted to Head of Research and Development for Miriam. She'll review today's ASLD presentation on our call today. Now, let's turn to an update on the launch. It's early days, but we're confident in the initial progress we've seen.
spk06: Peter? Thanks, Chris. Over the last 18 months, we've been quite busy building a world-class commercial team here at Merrill and conducting a lot of work to prepare for the launch of Live Marley. It's clear that these efforts have paid off as the Live Marley commercial launch is off to a strong start. Today, I'm excited to share early insights into our achievements following just over a month of commercial availability. Given that the FDA approval of Liv Marley occurred on September 29th, we are not providing specific revenue or associated commercial metrics in this third quarter earnings report, as there was no product revenue recognized in the third quarter. We will provide an update on Q4 results early next year. That being said, we're very pleased with what has been a great start in the early weeks of commercialization. From an access perspective, we've seen faster-than-expected acceptance by payers. We previously communicated that we expected the majority of allogel syndrome patients to have a reimbursable pathway sometime in the first half of 2022, which was based on the observed launch performance of several comparable rare disease medicines. As of today, the majority of Allergy Health Syndrome patients in the United States have a reimbursable pathway, exceeding our access goal by several months. For example, the three largest commercial payers in the United States have reimbursable pathways established with claims approved for each major payer. On the Medicaid front, we've signed our CMS rebate agreement, and several states have added Livmarly as a reimburse product in their systems. We have also been very pleased by the receptivity to the Marley by healthcare professionals. Our field team has reached all of our top 125 accounts in October, and we have seen prescribing from the broad base of accounts and positions to date, ranging from the top programs in the country to smaller community-based centers. Feedback from patients and caregivers, as well as prescribers, on the Merum Access Plus program, or MAP, has been very positive. The goals of MAP include ensuring that patients have timely access to Lidmarli once prescribed, as well as minimizing any financial barriers. I'm pleased to say that MAP is delivering according to our expectations, as we've seen timely dispenses in the early weeks of launch. Turning to international, this past quarter, we announced that we have entered into a development and commercialization agreement with Takeda for Livmarli in Japan, leveraging their expertise in rare disease as well as GI hepatology. Beyond Japan, we've entered into licensing or distribution deals for Livmarli in each of Greater China, South Korea, Israel, the Middle East, Russia and the Baltics, and finally, Central and Eastern Europe. All of our commercialization partners in these geographies bring a tremendous depth of local knowledge and rare disease expertise, which nicely complements the capabilities of Mirim's own commercial team in the U.S. and Europe. We are very grateful to have such a strong and dedicated group of partners working towards ensuring as many patients as possible can benefit from Live Marley. Partnering discussions for additional geographies are ongoing, and we'll keep you updated on our progress there. There are tremendous opportunities ahead, both from a commercial standpoint, but also across our development programs. Ann will share more about our recent data and provide an update on our pipeline progress. Ann?
spk01: Thanks, Peter. In support of Liv Marley's approval, we remain committed to ongoing research and analysis to continue to further validate Liv Marley's utility in this disease. To that end, we're so excited by the data presented today at the ASLD annual meeting in a late-breaking oral presentation demonstrating significant improvement in event-free survival with Liv Marley compared to a natural history control cohort. This is a landmark data set for Allergy of Syndrome, and the first time an interventional drug has demonstrated improved event-free and transplant-free survival in this devastating disease. Presentation is available in the publication section of our website, and I will now share a few highlights with you. For patients with Allergy Syndrome, pruritus is a leading indication for liver transplantation, and the prognosis in this setting is quite troubling, with transplant-free survival among patients with Allergy Syndrome of only 41% by 18 1⁄2 years of age. And the presentation today evaluated six years of follow-up from the pooled Merrill-Left-About studies in Allergy Syndrome, keeping in mind that this is the largest interventional data set available in this rare disease. and compared it against the GALA Natural History Database, which includes over 1,600 patients, the largest natural history control cohort established for allogel syndrome. The goal of this assessment was to compare time to first clinical event between the two groups. The results demonstrated a striking 70% overall reduction for clinical outcomes of live-moderately treatment and a statistically significant improvement in six-year event-free survival with a p-value of less than 0.0001 and a hazard ratio of 0.305. In addition to event-free survival, the analysis showed statistically significant improvements in transplant-free survival, which evaluates transplantation and death only. And this also demonstrated a p-value of less than 0.0001 and a hazard ratio of 0.332. Multiple sensitivity and subgroup analyses were conducted to test the robustness of the data, and consistent findings were observed across these analyses. These data have been included in our submission to the European Medicines Agency for the treatment of cholestatic liver disease due to Allergy Syndrome, and we expect a decision from the EMA in the second half of 2022. Now, in a second late-breaking abstract, we also analyzed event-free survival, and this analysis was presented by Dr. Ron Sokol. This work demonstrated that bilirubin, serum bile acids, and pruritus were predictors of event-free and transplant-free survival. Sixty of 76 patients remained event-free at the time of this analysis with up to six years of treatment. And critically, the improvement of pruritus being predictive of event-free survival supports Liv Marley's impact on long-term outcomes. And these data may be helpful to inform medical management for patients treated with Liv Marley. Lastly, on the publications front, we're very excited that The Lancet published our pivotal ICONIC study following four years of treatment with Liv Marley in patients with allogeal syndrome. Now, outside of allogeal syndrome, Mirim's Merilixibat pipeline continues to progress. With respect to PFIC, we expect to announce top-line data from the Phase 3 March study in the second quarter of 2022. As a reminder, the March PFIC study enrolls all PFIC subtypes. Additionally, enrollment continues to gain momentum in the Embark Phase 2b study of Merilixibat in biliary atresia. Now, a brief update on Belixibat in the adult setting. We're committed to continue expanding the potential role of iBAT inhibition across cholestasis. Our Velixibat program builds on the learnings from our pediatric programs, and the adaptive design, potentially registration of Velixibat studies are currently underway. As a reminder, we have launched the Phase IIb VISTA study to evaluate Velixibat in adults with primary sclerosis and cholangitis, and the Phase IIb OHANA study to evaluate Velixibat in interhepatic cholestasis in pregnancy. And we expect interim analyses for both of these studies in 2022, and I'm excited to share that the VANTAGE primary biliary cholangitis study is active and currently screening patients. With all that said, we have a clear vision of NIRM's clinical programs, and we're very excited about the future of these indications. And on that note, I will turn the call over to Ian to provide an update on our financial health. Ian?
spk00: A comprehensive overview of our quarterly financials is available in the press release distributed earlier this afternoon and in the form 10Q filed with the SEC. You can find both in the investors section of our corporate website at mirrenfarmer.com. I'll provide an overview of what we believe to be the highlights from the third quarter of 2021, all of which position us well to support our current launch of Live Marley and our further development pipeline for both Maralixabat and Velixabat in their respective indications. First, from a revenue perspective, we received an upfront licence payment of $5 million from GC Pharma. Under this exclusive licensing agreement, GC Pharma has agreed to develop and commercialise Merlixabat in South Korea. Looking at operating expenses for the quarter ended September 30, 2021, our G&A expenses were $17.4 million. G&A investment increases in the third quarter of 2021 versus the third quarter of 2020 were primarily due to increased personnel and operational costs associated with the launch of Live Miley, as well as expenses related to general, legal, and public relation activities. R&D expenses were $30.5 million as compared to $16 million for the third quarter of 2020. The increase was driven by the following. collaboration program funding, increases related to the looks about clinical trial expenses for PSC, PBC and ICP, as well as related manufacturing activities supporting clinical supply and increases in personnel and other compensation related expenses. Neural remains well funded and at the close of the third quarter ended September 30th, 2021, we had cash, cash equivalents and investments of $205 million. In connection with the FDA approval of Liv Marley, we have received the Priority Review Voucher, or PRV. We intend to monetize the voucher, and along with this expected additional cash, the company has more than three years of runway. Of note, our financing arrangement with Oberlin Capital allows an additional $35 million of financing upon the approval of Liv Marley. Given the strength of our financial position and projected financial performance of the business, we have decided to forego this tranche of the structure. So, with that update, I'll turn the call over to Chris for any final comments. Chris?
spk07: Great. Thank you, Ian, and thank you to everyone who joined today. To close, Verum has made great strides as a company this quarter as we continue to advance the treatment of devastating liver diseases. Our launch is off to a great start thanks to the hard work we put into commercialization efforts ahead of the launch. The excitement for our launch really stems from the convincing data and excitement of treating physicians to have a new medicine for patients living with this terrible disease. And the data presented today shows the great potential we see with Marley. Before I close, I wanted to briefly recap our upcoming milestones. First, our algeal syndrome application is under review in Europe, and we're preparing for a potential launch in the second half of 2022. We plan to share top-line data from the Phase III March PFIC study of Merilixibet and PFIC in the second quarter of next year. And for Velixibet, a potentially registrational program in adult cholestasis expects interim analyses of the adaptive OHANA and VISTA studies in intrapatic cholestasis of pregnancy and primary sclerosing cholangitis next year. We are thrilled with our progress in the recent launch of Live Marley. We look forward to updating on continued achievements as we head into 2022. Thank you again for joining us. Operator, please open the line for questions.
spk02: Great. Thank you. We will now move on to the Q&A session. If you would like to register a question, please press star followed by one on your telephone keypads. If you change your mind, please press star followed by two. For those who have joined us online, please press the red flag icon. And the first question comes from Jessica Yee from JP Morgan. Jessica, please go ahead. Your line is open.
spk03: Hey, guys. Good afternoon. Thanks for taking my questions. First, when you guys said you'll provide an update on 4Q results early next year, are you suggesting that you might pre-announce 4Q results, or was that just a reference to the typical timeline when you report 4Q? And second, can you remind us maybe when in 22 we could expect to hear more from the interims for the Villexpat, Ohana, and Vistas trials, and what the communication to the street will look like for each of those?
spk07: Yeah, thanks for the question. So I'm starting with the first one on the update for the fourth quarter as we get into next year. To be totally transparent about it, we haven't decided yet on pre-announcement versus the typical filing timeline. So that's something that we'll work through as we get through the balance of the year here. certainly could be something that makes sense to pre-announce as we get towards conference season early in the year. And then on the Elixabat studies, the interim analyses for the OHANA and VISTA studies have a key difference that's worth highlighting as we talk about the potential for those analyses towards the fourth quarter of next year. And For the VISTA's PSC study, this is a closed interim. So it will be an adaptive closed interim with predefined rules on continuing the study and selecting a dose. All of this with an eye towards moving into a registrational portion of the study. All of this discussed and aligned with FDA on how that analysis plan will work and how the study conduct will lead towards a potentially registrational data set with that study alone for PSC. The OHANA ICP study will conduct its interim a little bit differently. It will be an open interim, and we will have data, at least headline data, from that interim to share and announce once we conduct that analysis.
spk02: Great. Thank you. Great. Thank you, Jessica. And our next question comes from Mani Faruha from SBB Lering. Please go ahead.
spk09: Thank you for the question. Apologies for the background noise. I'm standing on Middle Street in New York City at the moment. We made some comments on the majority of patients having a path to reimbursement and directionally around how to think about discounting. Should we think about the scale of where discounting falls is looking similar to the Medicaid minimum? Should it look more like other commercial rare disease assets? Or is this an asset for which discounting is likely to be a really small part of the story, given it's going through transplant centers specifically?
spk07: Thanks for the question, Manny. I'll look to Peter to give some color on our expectations there.
spk06: Thanks for the question, Manny. The answer is really more the latter of your comments there. The discounting here that you should expect is really in line with the statutory requirements to participate in the Medicaid program. That's the vast majority of what will drive the gross to net. There's no strategy beyond that internally.
spk09: Great. Thanks. As a follow-up, when you talk about a past reimbursement, How should we think about that? Should we anticipate that there will be some gap from patient-first diagnosis through presumably a hub process to receiving commercialized drugs? And should we think of that as looking kind of like the one to three months of the drugs in the world, a little bit shorter, a little bit longer? How should we think about the delay to that to flip to the reimbursable drugs?
spk06: Yeah. Yeah, thanks for the question on that. And, you know, we are really pleased with how the MAP program has performed so far. And you did get the correct steps in the process. Of course, there's a discharge of the diagnosis. In the case of algeal syndrome, you know, a lot of the patients are already diagnosed. and then a prescription, and then a fill. And, you know, what I can say at this point is we're really pleased with the timelines we've seen so far between prescription and fill. And that is one of the key goals of the MAP program, both to get patients access to the medicine on a timely basis and also, you know, to support the providers in terms of their goals. And, you know, just to kind of throw an anecdote out there, kind of in the early days, we have seen, you know, it's variable. There's different timelines associated with different payers, but we have seen dispenses occur as quickly as, you know, a handful of days after receiving that complete enrollment form and paperwork. Thanks, guys.
spk09: We have to get a little progress. Thanks, man.
spk02: Great. Thank you, Manny. And our next question comes from Josh Skimmer from Evercore ISI. Please go ahead.
spk04: Great. Thanks so much for taking the questions. Maybe first on the OHANA study, I guess since you've indicated that this could be a registration-enabling trial, what is it that you ultimately need to deliver to the FDA in terms of a registration package that may also, I guess, consider pregnancy outcomes? Thanks.
spk07: Thanks, Josh, for the question. Overall, the interaction with FDA has, similar to some of our other indications, has focused on pruritus. So for this setting, we do expect the endpoint for approval with FDA to be improvement in pruritus. The study looked at much more, so I'll actually pass it over to Pam to talk through some of the other endpoints and implications we see across the outcomes potential.
spk01: Yeah, thanks. Thanks for the question, Josh. So for ICP, just a little bit of background that you're probably already aware of, that these women present in the late second trimester or third trimester pregnancy with often significant pruritus, elevated serum bile acids. And we know that when serum bile acids are above 40 and above 100, that these women are at risk of having iatrogenic delivery or spontaneous preterm birth, and also in very extreme cases, stillbirth. There's also considered, so we'll look at all of the endpoints that are associated with poor fetal outcomes, including length of hospitalization stays, et cetera. So all of those are in the secondary part of the key analyses that we're conducting and will be part of our filing.
spk04: Just as a follow-up to that, what are the indications for early delivery? And as you think about, I guess, extending the gestational time, if serum bile acids haven't been normalized, is there a concern that the longer time in gestation could have some kind of adverse outcome on the fetus because of prolonged exposure to maybe not normal but potentially still elevated bile acids.
spk01: Yes, so we anticipate with Velixibat as with our experience with Merilixibat that there's a significant reduction in serum bile acids that you see in cholestatic liver disease. And this would expect it to be no different. So you see reductions hopefully in serum bile acid and that helps inform for medical decisions on leaving the baby in longer and maybe not having a iatrogenic delivery and lower stem bile acids. also are helpful for preterm spontaneous birth. We know that when kids are born early, that in premature children, that there is a lot of risk associated with that in and of itself. So keeping the baby in as long as possible is a goal. And lowering stern bile acid hopefully will help that.
spk04: And then maybe a couple of quick questions on the MergePFIC program now that there is a competitor drug approved in a number of markets. Is there any risk or concern that you may lose some patients from that trial onto an approved therapy? And given that there is an approved therapy, What are you looking for in the phase three results to continue to advance to filings that doesn't need to be kind of numerically better or is a comparable data set worth advancing, and if so, why?
spk07: Thanks for the question there. From just the study conduct standpoint, So far, what we're seeing, there's no real meaningful impact on the overall study conduct. And worth knowing that it's an international study, so it's actually in a number of countries, some of which may not have access to the newly approved agent at this point. So with many of these patients having enrolled over the prior time periods, there's actually some of them already on to the open label extensions as well. So this is just less of an issue. And in terms of the competitive profile for Liv Marley and PFIC and also in Allergy Syndrome as well, one of the big advantages we have in our program is the longevity of the data and the ability to present data like we did earlier today on six-year event-free survival impact of Liv Marley in these indications. And we have some data that's been previously presented in PFIC showing similar findings in PFIC2. So that gets paired with results from the March PFIC study next year that we're also optimistic that we'll see an improved response rate because of the increased dose that's involved in the ongoing study.
spk04: Great. Thanks very much.
spk02: Great. Thank you, Josh, for your question. And we will now move on to Ed Arth from HC Wayne-Moy. So please go ahead.
spk05: Great. Thank you for taking my questions. And congrats on all the recent progress, including today's presentation. I wanted to start with that, just given the really long the long effects that have now been shown with Marley. How does that inform discussions with payers? Have you seen hurdles that payers put in place, perhaps less than you had thought? Let me discuss that. And have you seen any changes declinations yet. I recognize it's very early still, and a lot of them are still going through it. But just wondering the overall sense of the payer engagement so far in the launch. Thanks for the question, Ed.
spk06: I'll let Peter jump into that one. Yeah, thanks for the question, Ed. You know, with regards to the U.S., and then I'll pivot to Europe, I think there's an important point there as well. You know, we invested early, and our field team was out engaging with payers back in the spring. And, you know, kind of for many payers, this is the first time they've even heard of algeo syndrome or they knew very little about it. So I think they've really come to understand. appreciate what is a very high unmet medical need. And these children really are robbed of their childhoods. And the safety NFC profile of Luke Marley, as has been presented in the recent Lancet publication with long-term follow-up, you know, really quite persuasive to them. And we think that's part of what we've seen, what we updated you on today, in terms of earlier than anticipated, you know, the reversible pathways. And, you know, with regards to the late-breaking abstract today and the best of ASLD natural history comparison to JALA, that actually is part of our European package, and we've had a number of interactions with European payers. And it's just really exciting to have that kind of data as part of the package and the initial HTA, health technology assessment stages, to build long-term outcomes compared to a natural history cohort. So those data have, quite frankly, played very well in those conversations and have us at Miriam excited about the European launches in the second half of next year.
spk05: Okay, great. And then just one follow-up. Regarding Vantage, I know you just started screening patients here, but given that there are a couple other competitive programs in late-stage development here, wondering what your overall impression is of the bar in terms of – Not necessarily approval, which is well-known, but more about commercial acceptance and the competitive landscape there. Recognize it's early, but just wanted to get your thoughts.
spk07: And thanks for that question, Ed. Actually, there's an important element of the strategy for Vantage that is worth highlighting in this As you're alluding to, there is some competitive activity in studies for kind of a second or third line setting of PVC with agents that are focused on alkaline phosphatase as a primary endpoint for use as a surrogate marker for approval. And our approach for Velixibet in PVC is quite different. So we are not using alkaline phosphatase as the primary endpoint, but using puritis, again, as the outcome for approval and the primary endpoint for the study, which we expect has the possibility of being registrational in the second portion of the study. In terms of what that means from a competitive dynamic and where the looks of that can fit in the treatment paradigm, it really is line of therapy agnostic. Pteritis can occur in PBC with lower or elevated alkaline phosphatase levels. So think of it as a first or second line agent that can be kind of on a parallel track to some of the other competitive trials that are in the second or third line settings.
spk05: Okay. That's helpful. Thank you.
spk02: Great. Thank you for your question. We will now move to Yasmeen Rayini from Piper Sandler. Yasmeen, please go ahead. Your line is open.
spk08: Hey, everyone. It's Dave on the line for Yasmeen. Thanks for taking my question. So on a percentage basis, I was hoping you could shed some color on what percent of the 120 key accounts that cover the 80% of ALGS lives. what so what percent of that have have an awareness of with marley and have started to write scripts and add a few follow-up questions after that yeah thanks for the question there as you mentioned it's very early days to provide specific metrics but um peter can speak
spk06: We've interacted with all of the 125 since in October and have been able, in different ways, been able to kind of gain access and raise awareness. So it's not a large universe out there, and I'm pleased that we've been able to get out there. And in terms of where the prescriptions are coming from, Yeah, I think it's early days here six weeks into launch to get into specific quantification. Other than to say we're really encouraged by the sort of broad uptake we've seen from both the top centers in the country, but also the smaller regional accounts. So I think that's a good sign for where things stand and look forward to updating you more as we move through the launch process.
spk08: Great. Thanks for the additional color. here. With regard to the late-breaking abstract you guys presented at ASLD, how similar were the baseline characteristics between the patients on the Marley compared to the Gallup cohort, and what efforts are being made to use this data to educate treating physicians, and how do you think that will impact adoption down the road?
spk01: Yeah, thanks for the question. I'll start off, and then with regard to adoption, I'll hand over to Peter for that. So, yeah, we're just really excited about this analysis. It's been a labor of, you can imagine, six years of involvement from these patients and physician community to get to this database and a lot of effort by the GALA Natural History Study Group. And this analysis we compared with Marley to a Natural History Gala Control cohort. And the way that we ensured that there was similarity between baseline characteristics was through a pre-specified, very rigorous selection process in which outcomes were blinded and actually all of the robust methodologies, including sensitivity and subgroups, were included to try to ensure robustness, statistical robustness of the clinical efficacy. So the cohort selection, once the cohort was selected, and this is based on using key entry criteria from the Merrill-Luxabad studies to try to get a representative and appropriate control cohort, there is an assessment of comparability across the two groups. And this showed that there were similar disease severity between the two groups. This is looking at alkaline phosphatase, so ALT. ALP, AST, GGT, bilirubin, et cetera. And we found that both of these were well aligned. There were sensitivities on potential variables. So this is where we looked at adjustments at baseline. And this included everything from ALP, bilirubin, age, GGT, sex, year of birth, et cetera. All of these were analyzed using different adjustment analyses. I think it's important to note that we found that there were no statistical differences between the two groups at baseline, with the exception of serum bile acid, where it was higher in the Merilixibat treatment group. And I think also important to note that SBA is not commonly collected in the real world. So GALA includes a subset of these data. But we ran subgroup analyses on that, as well as several other components using different index times, when do you start the clock for the Gallup cohort, looking at transplant-free survival, and also pruning analysis to adjust for immortal time bias. So taking all of this together, the pre-specified analysis that I just mentioned with all of these sensitivities and subgroup analyses really demonstrate the robustness of the data with highly statistically significant improvements in event-free and transplant-free survival between the two cohorts. And maybe I'll, yeah. Sure, and I'll hand to Peter. Sorry, go ahead. All right. I'll hand to Peter for the, did you have another question for me?
spk08: Well, I did have a follow-up question, but I mean, if you want me to continue. Okay, great. I appreciate it. Yeah, yeah, thanks. So my final question here, and this actually provides sort of a good segue. in your view, is the Gallup database to the real-world setting? And were there any subset analysis that you can discuss of the data where either liver transplantation or biliary diversion surgery or decompensation events, perhaps patients with those that could have a greater event, or sorry, greater benefit over others with LeVarlier's?
spk01: Yeah, so I think there's a really – we had another late-breaker presentation, which was a poster, and the first author is Ron Sokol. this really goes hand-in-hand nicely with the GALA natural history comparison and shows predictors of event-free survival. So we looked at our data and tried to identify what are the predictors of event-free survival and transplant-free survival, and we found, I think importantly for this discussion, that improvement in pruritus, a one-point improvement in pruritus specifically, was predictive of event-free and transplant-free survival, where 88% of patients who had that improvement remains event-free and transfer-free.
spk08: Great. I appreciate your time, and I appreciate you answering all of my questions. Thanks a lot. Yeah, thanks for the questions.
spk02: Great. Thank you so much. And our next question comes from Brian Scorney. Oh, I'm sorry. Our next question comes from Steve Seathouse from Raymond James. Please go ahead.
spk10: Hi there, this is Ryan Detron for Steve Seedhouse. I just want to ask, how many genetic subtypes will be reported on in the March top line readout? And then I have a follow-up question.
spk07: Yeah, thanks for the question there. The March PFIC study includes really all genetic subtypes of PFIC, and we do see and have seen broad representation across the multiple subtypes in the study. randomized placebo-controlled data for all T6 subtypes included in the study that we'll be able to report on.
spk10: Okay, terrific. And then also, I was wondering if you could give us a little more detail on what your expectations for height and weight and Z-score are in the Phase III MARCH study. There was some competitor data out at ASLD.
spk07: That was interesting. I think for the follow-up on that, I'll pass it over to Pam to share some of what we've seen in other studies, but worth noting that at six months in, we wouldn't expect to see the full effect, and some of this happens over time periods longer than just that first six months. So we do have an open-label extension as part of this study that we will continue to gather
spk01: Yeah, thanks. So yeah, happy to speak about this for a second. So in our indigo phase two study, we've presented data on patients who had a serum bile acid response. And those patients who have a serum bile acid response, and we know that this is predictive of transplant-free survival. This was shown by NAPID, which is the Natural History Registry for PFIC. And when we applied those serum bile acid thresholds to our study, we saw a 100% transplant-free survival in patients who have serum bile acid response. And in those patients, the growth data was statistically significant. um um as was uh alt ast uh and uh pete's quality of life and of course high z-score and also pruritus of course so across you see this broad base improvement in clinical parameters, including growth, as you're stating, in patients who have serum bile acid control. And so, we presented five years of data on this. As Chris said, we'll continue to look at the March PfeC Phase III study six months as early, but as we know, patients are continuing into an open-label extension. So, certainly more to come across all PfeC subtypes on this.
spk10: Okay. Thank you very much. Thanks for the question.
spk02: Great. Thank you, Steve. And as a reminder, if you would like to ask a question, please press star followed by 1 on your telephone keypads. That is star followed by 1 on your telephone keypads.
spk07: Great, operator. I think we can close the queue for further questions. show my problem i'll now pass over to chris p for final remarks and thanks again to everyone for joining today's call and for your interest in miram it's an exciting time with the launch of live marley and today's presentation of groundbreaking data showing the potential to improve long-term outcomes we look forward to sharing further updates as the launch progresses thank you and goodbye thank you everybody for joining today's call you may now disconnect your lines
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