Earnings Call Transcript - MIRM Q3 2021

Operator, Operator

Hello everyone and welcome to the Mirum Pharmaceuticals third quarter business update conference call. My name is Victoria and I will be coordinating your call today. Operator Instructions. I will now hand you over to your host, Ian Clements, Chief Financial Officer. Ian, please go ahead.

Ian Clements, Chief Financial Officer

Thanks Victoria and good afternoon everyone. I would like to welcome you to Mirum Pharmaceuticals third quarter 2021 conference call. I am joined today by our President and CEO, Chris Peetz, Pam Vig, Head of Research and Development, and Peter Radovich, Chief Operating Officer. Earlier this afternoon, Mirum 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 would like to remind you that during the course of this conference call, we will be making certain forward-looking statements about Mirum and our programs based on management's current expectations, including statements regarding Mirum'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 Mirum's Form 10-Q for the quarter ended September 30, 2021 and any subsequent reports filed with the SEC. With that said, I would like to turn the call over to Chris Peetz. Chris?

Chris Peetz, President and Chief Executive Officer

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 LIVMARLI for cholestatic pruritus in patients one year and older with Alagille syndrome, the first-ever approved medicine in this indication and the first FDA-approved product from Mirum. LIVMARLI's launch is a tremendous achievement and I am very proud of our team for the impressive stride made this quarter. We are all humbled and excited about what it means to the eligible Alagille community and I would again extend my thanks and appreciation to patients, parents, caregivers, investigators, advocates and employees that got it done. The hard work of the Mirum team is delivering results. Our prelaunch preparations have resulted in a strong starting market. Today, Peter will speak to our commercial efforts, including an update on the many partner companies multiplying our efforts to launch LIVMARLI around the world. This quarter also witnessed several important milestones from our clinical and regulatory efforts. We submitted a marketing authorization application in Europe for LIVMARLI for the treatment of cholestatic liver disease in patients with Alagille syndrome. And just today, at the AASLD Liver Meeting, the Global Alagille Alliance presented landmark data that was part of that submission. These data showed a highly significant improvement in transplant-free survival for patients in LIVMARLI 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 the Liver Meeting recognition. We believe these results are nothing short of remarkable. Before turning the call over to Peter, I would like to share a couple of updates on the leadership team. First, I would like to thank Dr. Ed Tucker, who has served as Mirum's Chief Medical Officer since 2019, supporting the application and approval of LIVMARLI. We wish him the best of luck as he embarks now on his next professional endeavor. Second, I am excited to share that our Chief Scientific Officer, Dr. Pam Vig, is being promoted to Head of Research and Development for Mirum. She will review today's AASLD presentation on our call. Now let's turn to an update on the launch. It's early days, but we are confident in the initial progress we have seen. Peter?

Peter Radovich, Chief Operating Officer

Thanks Chris. Over the last 18 months, we have been quite busy building a world-class commercial team here at Mirum and conducting a lot of work to prepare for the launch of LIVMARLI. It's clear that these efforts have paid off as the LIVMARLI commercial launch is off to a strong start. Today, I am excited to share early insights into our achievements following just over a month of commercial availability. Given that the FDA approval of LIVMARLI occurred on September 29, 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 are very pleased with what has been a great start in the early weeks of commercialization. From an access perspective, we have seen faster-than-expected acceptance by payers. We previously communicated that we expected the majority of Alagille 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 Alagille 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 signed our CMS rebate agreement and several states have added LIVMARLI as a reimbursed product in their systems. We have also been very pleased by the receptivity to LIVMARLI by healthcare professionals. Our field team has reached all of our top 125 accounts in October and we have seen prescribing from a broad base of accounts and physicians 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 Mirum Access Plus program, or MAP, has been very positive. The goals of MAP include ensuring that patients have timely access to LIVMARLI once prescribed as well as minimizing any financial barriers. I am pleased to say that MAP is delivering according to our expectations as we have 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 have 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 Mirum'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 LIVMARLI. Partnering discussions for additional geographies are ongoing and we will keep you updated on our progress there. There are tremendous opportunities ahead, both from a commercial standpoint but also across our development programs. Pam will share more about our recent data and provide an update on our pipeline progress.

Pamela Vig, Head of Research and Development

Thanks Peter. In support of LIVMARLI's approval, we remain committed to ongoing research and analyses to continue to further validate LIVMARLI's utility in this disease. To that end, we are so excited by the data presented today at the AASLD Annual Meeting in a late-breaking oral presentation demonstrating significant improvement in event-free survival with LIVMARLI compared to a natural history control cohort. This is a landmark data set for Alagille syndrome and the first time an interventional drug has demonstrated improved event-free and transplant-free survival in this devastating disease. The presentation is available in the Publication section of our website and I will now share a few highlights with you. For patients with Alagille 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 Alagille syndrome of only 41% by 18.5 years of age. The presentation today evaluated six years of follow-up from the pooled maralixibat studies in Alagille 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 Alagille syndrome. The goal of this assessment was to compare time to first clinical events between the two groups. The results demonstrated a striking 70% overall reduction for clinical outcomes with LIVMARLI 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 analyses 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 LIVMARLI for the treatment of cholestatic liver disease due to Alagille 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 LIVMARLI's impact on long-term outcomes. These data may be helpful to inform medical management for patients treated with LIVMARLI. Lastly, on the publications front, we are very excited that The Lancet published our pivotal ICONIC study following four years of treatment with LIVMARLI in patients with Alagille syndrome. Now outside of Alagille syndrome, Mirum's maralixibat pipeline continues to progress. With respect to PFIC, we expect to announce topline data from the Phase III 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 IIb study of maralixibat in biliary atresia. Now a brief update on volixibat in the adult setting. We are committed to continue expanding the potential role of IBAT inhibition across cholestasis. Our volixibat program builds on the learnings from our pediatric programs and the adaptive design potentially supports registrational volixibat studies that are currently underway. As a reminder, we have launched the Phase IIb VISTAS study to evaluate volixibat in adults with primary sclerosing cholangitis and the Phase IIb OHANA study to evaluate volixibat in intrahepatic cholestasis of pregnancy. We expect interim analyses for both of these studies in 2022. And I am excited to share that the VANTAGE primary biliary cholangitis study is active and currently screening patients. With all of that said, we have a clear vision of Mirum's clinical programs and we are 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?

Ian Clements, Chief Financial Officer

Thanks Pam. A comprehensive overview of our quarterly financials is available in the press release distributed earlier this afternoon and in the Form 10-Q filed with the SEC. You can find both in the Investors section of our corporate website at mirumpharma.com. I will 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 LIVMARLI and our further development pipeline for both maralixibat and volixibat in their respective indications. First, from a revenue perspective, we received an upfront license payment of $5 million from GC Pharma. Under this exclusive licensing agreement, GC Pharma has agreed to develop and commercialize maralixibat 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 LIVMARLI as well as expenses related to general, legal and public relations 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 volixibat clinical trial expenses for PSC, PBC and ICP as well as related manufacturing activity supporting clinical supply and increases in personnel and other compensation-related expenses. Mirum remains well funded. At the close of the third quarter ended September 30, 2021, we had cash, cash equivalents and investments of $205 million. In connection with the FDA approval of LIVMARLI, we have received a priority review voucher, or PRV. We intend to monetize the voucher. Along with this expected additional cash, the company has more than three years of runway. Of note, our financing arrangement with Oberland Capital allowed for an additional $35 million of financing upon the approval of LIVMARLI. Given the strength of our financial position and projected financial performance of the business, we have decided to forgo this tranche of the structure. So with that, I will turn the call over to Chris for any final comments. Chris?

Chris Peetz, President and Chief Executive Officer

Great. Thanks Ian. And thank you to everyone for joining today. To close, Mirum 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 enthusiasm of treating physicians to have a new medicine for patients living with this terrible disease. The data presented today shows the great potential we see in LIVMARLI. Before I close, I wanted to briefly recap our upcoming milestones. First, our Alagille syndrome application is under review in Europe and we are preparing for a potential launch in the second half of 2022. We plan to share topline data from the Phase III MARCH-PFIC study of maralixibat in PFIC in the second quarter of next year. And for volixibat, a potentially registrational program in adult cholestasis expects interim analyses with the adaptive OHANA and VISTAS studies in intrahepatic cholestasis of pregnancy and primary sclerosing cholangitis next year. We are thrilled with our progress and the recent launch of LIVMARLI. We look forward to updating on the continued achievements as we head into 2022. Thank you again for joining us. Operator, please open the line for questions.

Operator, Operator

And the first question comes from Jessica Fye from JPMorgan. Jessica, please go ahead. Your line is open.

Jessica Fye, Analyst (JPMorgan)

Hi guys. Good afternoon. Thanks for taking my questions. First, when you said you will provide an update on 4Q results early next year, are you suggesting that you might preannounce 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 2022 we could expect to hear more for the interims for the volixibat OHANA and VISTAS trials? And what the communication to the Street will look like for each of those?

Chris Peetz, President and Chief Executive Officer

Yes. Thanks for the question. So I will start 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 preannouncement versus the typical filing timeline. So that's something that we will work through as we get through the balance of the year here. Certainly, it could be something that makes sense to preannounce as we get towards conference season early in the year. And then on the volixibat studies, the interim analyses for the OHANA and VISTAS 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. For the VISTAS-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 the 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.

Pamela Vig, Head of Research and Development

Yes. For OHANA, the open interim is designed to generate headline data that we can communicate, while VISTAS has the closed adaptive interim built to select dose and adapt the study with the goal of supporting a registrational path for PSC, consistent with our FDA discussions.

Jessica Fye, Analyst (JPMorgan)

Great. Thank you.

Operator, Operator

Great. Thank you Jessica. And our next question comes from Mani Foroohar from SVB Leerink. Please go ahead.

Mani Foroohar, Analyst (SVB Leerink)

Hi guys. Thanks for taking the question. I apologize for the background noise. I am standing in the middle of the street in New York City at the moment. You made some comments on the majority of patients that got a path to reimbursement and directionally around how to think about discounting. Should we think about the scale of where discounting falls? Is it looking similar to the Medicaid minimum? Is it more like other commercial rates on these assets? Or is this an asset for which discounting is likely to be a really small part of the story given its flow to transplant centers specifically?

Chris Peetz, President and Chief Executive Officer

All right. Thanks for the question, Mani. I will look to Peter to give some color on our expectations there.

Peter Radovich, Chief Operating Officer

Yes. Thanks for the question, Mani. The answer is really more the latter of your comments. 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.

Mani Foroohar, Analyst (SVB Leerink)

Great. Thanks. And as a follow-up, you talked about a path to reimbursement. So 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 receive and commercial drug? And should we think about looking kind of like one to three months of lag around the world, a little bit further or a little bit longer? And how do you think about the delay to that sort of complete enrollment as a reimbursable drug?

Peter Radovich, Chief Operating Officer

Yes. Thanks for the question on that. We are really pleased with how the MAP program has performed so far. And you did give the correct steps in the process. Of course, there's a start at diagnosis — in the case of Alagille syndrome, a lot of the patients are already diagnosed — then a prescription and then a fill. What I can say at this point is we are really pleased with the timelines we have seen so far between prescription and fill. That is one of the key goals of the MAP program, both to get patients access to medicine on a timely basis and also to support the providers in terms of their goals. Just to throw an anecdote out there — it's variable, there are different timelines, especially with different payers — but we have seen dispenses occur as quickly as a handful of days after receiving a complete enrollment form and paperwork.

Mani Foroohar, Analyst (SVB Leerink)

Okay. Thanks guys. Congrats on all the progress.

Chris Peetz, President and Chief Executive Officer

Thanks Mani.

Operator, Operator

Great. Thank you Mani. And our next question comes from Josh Schimmer from Evercore ISI. Please go ahead.

Josh Schimmer, Analyst (Evercore ISI)

Good. Thanks very much for taking the questions. Maybe first on the OHANA study, since you have 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 consider pregnancy outcomes?

Chris Peetz, President and Chief Executive Officer

Thanks, Josh, for the question. Overall, the interaction with FDA in 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 looks at much more, so I will actually pass it over to Pam to talk through some of the other endpoints and implications we see across the outcomes potential.

Pamela Vig, Head of Research and Development

Thanks. For intrahepatic cholestasis of pregnancy (ICP), just a little bit of background: these women present in the late second trimester or third trimester of pregnancy often with significant pruritus and elevated serum bile acids. We know that when serum bile acids are above 40 and above 100, these women are at increased risk of iatrogenic delivery or spontaneous preterm birth and also, in very extreme cases, stillbirth. So we will look at all of the endpoints that are associated with poor fetal outcomes, including length of hospitalization stays, and those are in the secondary part of the key analyses that we are conducting and will be part of our filing.

Josh Schimmer, Analyst (Evercore ISI)

Just as a follow-up to that. What are the indications for early delivery? And as you think about extending the gestational time, if serum bile acids haven't been normalized, is there a concern that 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?

Pamela Vig, Head of Research and Development

Yes. We anticipate with volixibat, as with our experience with maralixibat, that there will be a significant reduction in serum bile acids that you see in cholestatic liver disease, and we expect it to be no different here. So you would see reductions in serum bile acids and that would help inform medical decisions around leaving the baby in longer and potentially avoiding iatrogenic delivery. Lower serum bile acids are also helpful for reducing the risk of spontaneous preterm birth. We know that when children are born early there are many risks associated with prematurity, so keeping the baby in as long as possible is a goal and lowering serum bile acids hopefully will help that.

Josh Schimmer, Analyst (Evercore ISI)

Got it. Helpful. And then maybe a couple of quick questions on the merged MARCH-PFIC 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 into an approved therapy? And given that there is an approved therapy, what are you looking for in the Phase III results to continue to advance to filings? Does it need to be numerically better or a comparable data set worth advancing? If so, why?

Chris Peetz, President and Chief Executive Officer

Thanks for the question. From a study conduct standpoint, so far what we are seeing is there is no meaningful impact on the overall study conduct. It's worth noting that the study is international, so it's actually in a number of countries, some of which may not have access to the approved agent at this point. Many patients who enrolled earlier are already in the open-label extension as well, so this is less of an issue operationally. In terms of the competitive profile for LIVMARLI in PFIC and Alagille syndrome, one of the big advantages we have in our program is the longevity of the data and the ability to present long-term outcomes like we did today showing six-year event-free survival impact. We have data previously presented in PFIC showing similar findings in PFIC 2. That, paired with results from the MARCH-PFIC study next year, gives us optimism that we will see an improved response rate because of the increased dose used in the ongoing study.

Josh Schimmer, Analyst (Evercore ISI)

Okay. Thanks very much.

Operator, Operator

Great. Thank you, Josh. And we will now move on to Ed Arce from H.C. Wainwright. Sir, please go ahead.

Ed Arce, Analyst (H.C. Wainwright)

Great. Thank you for taking my questions. And congrats on all the recent progress, including today's presentation. I wanted to start with, given the really long effects that have now been shown with LIVMARLI, how does that inform discussions with payers? Are you seeing hurdles that payers put in place perhaps less than you had thought? Have you seen any denials 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.

Chris Peetz, President and Chief Executive Officer

Ed, thanks for the question. I will let Peter jump into that.

Peter Radovich, Chief Operating Officer

Yes. Thanks for the question, Ed. With regards to the U.S., we invested early and our sales team has been engaging with payers for some time. For many payers, this was the first time they had heard of Alagille syndrome or they knew very little about it, so they have come to appreciate the very high unmet medical need and the safety and efficacy profile of LIVMARLI. The Lancet publication with long-term follow-up has been persuasive. We think that's part of what we've seen in terms of earlier-than-anticipated reimbursable pathways. Regarding the late-breaking abstract today and the Best of ASLD recognition, that is part of our European package and we have had a number of interactions with European payers. It's exciting to have that kind of data as part of the initial health technology assessment stages to demonstrate long-term outcomes compared to a natural history cohort. Those data have played very well in those conversations and have us at Mirum excited about potential European launches in the second half of next year.

Ed Arce, Analyst (H.C. Wainwright)

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 of other competitive programs in late-stage development, what's your overall impression of the bar in terms of not necessarily approval, but commercial acceptance and competitive landscape there? Recognize it's early, but I just wanted to get your thoughts.

Chris Peetz, President and Chief Executive Officer

Thanks for that question, Ed. There's an important element of strategy for VANTAGE worth highlighting relative to the competitive set in PBC. Some competitive activity in PBC is focusing on alkaline phosphatase (ALP) as a primary endpoint and surrogate marker. Our approach for volixibat in PBC is different: we are not using ALP as the primary endpoint but are focusing on pruritus as the primary endpoint, which we expect could be registrational in the second portion of the study. From a competitive dynamic perspective, volixibat can fit in the treatment paradigm as pruritus is line-agnostic — it can occur in PBC regardless of ALP levels. So think of volixibat as an agent that could be used in first or second line and on a parallel track to some other competitive trials targeting biochemical surrogates.

Ed Arce, Analyst (H.C. Wainwright)

Okay. That's helpful. Thank you.

Operator, Operator

Great. Thank you, Ed. We will now move to Yasmeen Rahimi from Piper Sandler. Yasmeen, please go ahead. Your line is open.

Dave Amsellem, Analyst (on behalf of Yasmeen, Piper Sandler)

Hi everyone. It's Dave on the line for Yasmeen. Thanks for taking my question. So on a percentage basis, I was hoping if you could shed some color on what percent of the 125 key accounts that cover the 80% of Alagille lives have awareness of LIVMARLI and have started to write scripts? And I have a few follow-up questions after that.

Chris Peetz, President and Chief Executive Officer

Thanks for the question. As we mentioned, it's very early days to provide specific metrics. Peter can speak to some of the color of what we are seeing out there.

Peter Radovich, Chief Operating Officer

Yes. Thanks Chris. We have interacted with all of the top 125 since October, and have in different ways been able to gain access and raise awareness. It's a relatively small universe. I'm pleased that we've engaged them. In terms of where the prescriptions are coming from, it's early — six weeks into launch — so beyond saying we are encouraged by the broad uptake we've seen from both top centers and smaller regional accounts, it's a little early for more specific quantification. That's a good sign for how things stand and we look forward to updating you more as the launch progresses.

Dave Amsellem, Analyst (on behalf of Yasmeen, Piper Sandler)

Great. Thanks for the additional color. And then if we could switch gears to the abstract here. With regard to the late-breaking abstract you presented at AASLD, how similar were the baseline characteristics between the patients on LIVMARLI compared to the GALA cohort? And what efforts are being made to use this data to educate treating physicians? How do you think that will impact adoption down the road?

Pamela Vig, Head of Research and Development

Thanks. I'm happy to speak to that. We are very excited about this analysis. It represents six years of involvement from patients and the physician community to create these data and significant effort by the GALA Natural History Study Group. This analysis compared LIVMARLI-treated patients to a GALA natural history cohort. We ensured similarity between baseline characteristics through a pre-specified, rigorous selection process in which outcomes were blinded. We used robust methodologies including sensitivity and subgroup analyses to ensure statistical robustness. The cohort selection was based on key entry criteria from the maralixibat studies to get an appropriate control cohort. We assessed comparability across the two groups and found similar disease severity between the groups when looking at ALT, AST, GGT, bilirubin, and other markers; these were well aligned. We did find that serum bile acids were higher in the maralixibat treatment group at baseline. It's important to note serum bile acids are not commonly collected in the real world, so this subset includes fewer patients. We ran subgroup analyses on that as well as several other components using different index times and pruning analyses to adjust for immortal time bias. Taking all of this together, the pre-specified analyses including these sensitivities and subgroup analyses demonstrate the robustness of the data with highly statistically significant improvements in event-free and transplant-free survival between the two cohorts. Regarding education and adoption, Peter can speak to how we're using these data with clinicians and payers.

Dave Amsellem, Analyst (on behalf of Yasmeen, Piper Sandler)

Well, I did have a follow-up question, but I am going to contain it or I will go forever.

Pamela Vig, Head of Research and Development

Okay. I appreciate it.

Dave Amsellem, Analyst (on behalf of Yasmeen, Piper Sandler)

Yes. Thanks. So my final question here and the fact it's probably a good segue to that. How representative, in your view, is the GALA database to the real-world setting? And were there any subset analyses where either liver transplantation or biliary diversion surgery or decompensation events indicate patients who could have a greater benefit with LIVMARLI?

Pamela Vig, Head of Research and Development

Yes. We had another late-breaker poster presentation, first authored by Dr. Ron Sokol, which complements the GALA natural history comparison and shows predictors of event-free and transplant-free survival. We looked at our data to identify predictors and found that improvement in pruritus — specifically a one-point improvement — was predictive of event-free and transplant-free survival. Eighty-eight percent of patients who had that improvement remained event-free and transplant-free. These findings help identify which patients may derive greater long-term benefit and will be useful for clinical decision-making.

Dave Amsellem, Analyst (on behalf of Yasmeen, Piper Sandler)

Great. I appreciate the time and I appreciate you answering all of my questions and thoughts.

Chris Peetz, President and Chief Executive Officer

Thanks for the question.

Operator, Operator

Great. Thank you very much. And our next question comes from Brian Skorney. Our next question comes from Steve Seedhouse from Raymond James. Please go ahead.

Ryan Deschner, Analyst (on behalf of Steve Seedhouse, Raymond James)

Hi everybody. This is Ryan Deschner on for Steve Seedhouse. I just want to ask how many genetic subtypes will be reported on in the MARCH topline readout? And then I have a follow-up question.

Chris Peetz, President and Chief Executive Officer

Thanks for the question. The MARCH-PFIC study includes all genetic subtypes of PFIC. We see and have seen broad representation across multiple subtypes in the study. We will be able to report randomized, placebo-controlled data for all PFIC subtypes included in the study.

Ryan Deschner, Analyst (on behalf of Steve Seedhouse, Raymond James)

Okay. Terrific. And then also, could you give us a little more detail on what your expectations for height and length z-scores are in the Phase III MARCH study? There were some competitor data at ASLD that was interesting.

Chris Peetz, President and Chief Executive Officer

I will pass that to Pam to share some of what we have seen in other studies. Worth noting that at six months we wouldn't necessarily expect to see the full growth effect, and some of this happens over longer time periods. We have an open-label extension as part of the study that will continue to gather that data.

Pamela Vig, Head of Research and Development

Yes. In our INDIGO Phase II study, we presented data on patients who achieved a serum bile acid response. Those patients, for whom serum bile acid response is predictive of transplant-free survival (as shown by the NAPPED natural history registry), showed 100% transplant-free survival in the responders. In those patients the growth data was statistically significant as were improvements in ALT, AST and patient-reported quality of life, and, of course, pruritus. You see broad-based improvement in clinical parameters including growth in patients who achieve serum bile acid control. We have presented up to five years of data on this. As Chris said, MARCH has a six-month readout but patients continue into an open-label extension, so more data will follow across PFIC subtypes.

Ryan Deschner, Analyst (on behalf of Steve Seedhouse, Raymond James)

Okay. Thank you very much.

Chris Peetz, President and Chief Executive Officer

Thanks for the question.

Operator, Operator

Operator Instructions.

Chris Peetz, President and Chief Executive Officer

Operator, I think we can close the queue if there are no further questions.

Operator, Operator

Sure. No problem. I will now pass it over to Chris Peetz for final remarks.

Chris Peetz, President and Chief Executive Officer

Great. And thanks again to everyone for joining today's call and for your interest in Mirum. It's an exciting time with the launch of LIVMARLI 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.

Operator, Operator

Thank you everybody for joining today's call. You may now disconnect your lines.