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.

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 program is based on managements' 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 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?

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 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 strife made this quarter. We are all humbled and excited about what it means to the eligible Alagille community and I would like to again the 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 preparation 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 revocation of LIVMARLI. in Europe 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 CMO since 2019, supporting the application and approval of LIVMARLI, who is leading the company. We wish him the best of luck as he embarks now in 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 ASLD presentation on our call today. 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?

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 the 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,…

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. 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. And 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 of 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…

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 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 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. And 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. And 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?

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

Hi guys. Good afternoon. Thanks for taking my questions. First, when you guys 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 time line when your 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?

Yes. Thanks for the question. So I am 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 preannouncement versus the typical filing time line. 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. And 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 FDA on how that analyses 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 analyses.

Great. Thank you.

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

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 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 sort of look more like other commercial rate 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?

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

Yes. Thanks for the question, Mani. 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 Medicaid program. That's the vast majority of what will drive the gross to net. There's no strategy beyond that internally.

Great. Thanks. And as a follow-up, you talked about a path to reimbursement. So how should we think about that as, should we anticipate that there will be some gap from patient first diagnosis through presumably a hub process to receive and commercialize drug? And should we think about as looking kind of like one to three months of listing 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?.

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 of the diagnosis in the case of Alagille syndrome, a lot of the patients are already diagnosed and then a prescription and then a fill. And what I can say at this point is, we are really pleased with the time lines we have 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 medicine on a timely basis and also to support the providers in terms of their goals. And just to kind of throw an anecdote out there kind of an early days, we have seen, it's variable, there's different time lines, 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.

Okay. Thanks guys. Congrats on all the progress.

Thanks Mani.

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

Good. Thanks very much for taking the questions. Maybe first on the OHANA study, I guess, 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, I guess, consider pregnancy outcomes?

Thanks, Josh, for the question. Overall, the interaction with FDA has, 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.

Yes. Thanks for the question, Josh. So for ICP, just a little bit of background that you are probably already aware of that these women present in the late second trimester or third trimetric pregnancy with often significant pruritus, elevated serum bile acid. 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 a stillbirth. There's also considered, so we will 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 are conducting and will be part of our filing.

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?

Yes. So we anticipate with volixibat as with our experience with maralixibat that there is 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 acids and that helps inform for medical decisions on leaving the baby in longer and maybe not having a iatrogenic delivery and the lower serum 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 lower serum bile acids hopefully will help that.

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 kind of numerically better or say a comparable data set worth advancing? And if so, why?

Thanks for the question there. From just the study conduct standpoint, so far what we are seeing, there is 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 approved, nearly approved agent at this point. So with many of these patients having enrolled over the prior time periods have actually some of them are already onto the open label extension as well. So this is less of an issue. And in terms of the competitive profile for with LIVMARLI and PFIC and also in Alagille 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 LIVMARLI in these indications. And we have some data that's been previously presented in PFIC showing similar findings in PFIC 2. So that gets paired with results from the MARCH-PFIC study next year that we are also optimistic that we will see an improved response rate because of the increased dose that's involved in the ongoing study.

Okay. Thanks very much.

Great. Thanks you, Josh,, for your question. And we will now move on Ed Arce from H.C. Wainwright. Sir, please go ahead.

Great. Thank you for taking my questions. And congrats on all the recent progress, including today's presentation. I wanted to start with, just given with 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, maybe discuss that? And have you seen any 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.

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

Yes. Thanks for the question, Ed. With regards to the U.S. and then I will pivot to Europe, I think there's an important point there as well. We invested early and our sales team is out engaging with payers back in this ring. And kind of for many payers, this is the first time they have even heard of Alagille syndrome or they knew very little about it. So I think they have really come to appreciate what is a very high unmet medical need and these children really are robbed of their childhood and the safety and efficacy profile of LIVMARLI as has been presented in the recent Lancet publication with long-term follow-up, really, really quite persuasive to them. And we think that's part of what we have seen all we updated you on today in terms of earlier than anticipated reimbursable pathways. And with regards to the late-breaking abstract today and the Best of ASLD natural history comparison to Alagille, that actually is part of our European package and we have 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 be able 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 Mirum excited about the European launches in the second half of next year.

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 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 competitive landscape there? Recognize it's early, but I just wanted to get your thoughts.

Yes. Thanks for that question, Ed. Actually, there's an important element of the strategy for VANTAGE that is worth highlighting in the competitive set in PBC. And as you are alluding to, there is some competitive activity in studies for kind of a second or third line setting of PBC with agents that are focused on alkaline phosphatase as a primary endpoint for use of a surrogate marker for approval. And our approach for volixibat in PBC is quite different. So we are not using alkaline phosphatase as the primary endpoint, but using pruritus, again, as the outcome for approval and the primary endpoint for the study and 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 volixibat can fit in the treatment paradigm, it really is line of therapy agnostic. Pruritus 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 kind of the second or third line setting.

Okay. That's helpful. Thank you.

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

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 120 key accounts that cover the 80% of Alagille lives? So what percent of that have an awareness with LIVMARLI and have started to write scripts? And I have a few follow-up questions after that.

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

Yes. Thanks Chris. And we have interacted with all of the 125 since October. And have in different ways, been able to kind of gain access and raise awareness. So it's not a large universe out there. I am pleased that we have done a little to get out there. And in terms of where the prescriptions are coming from, I think it's early days here six weeks into launch, given the specific quantification other than to say, we are really encouraged by those sort of broad uptake we have 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.

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 guys 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? And how do you think that will impact adoption down the road?

Yes. Thanks for the question. I will start off and then with regard to adoption, I will hand over to Peter for that. So yes, we are just really excited about this analyses. 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 means if we compared with LIVMARLI to a natural history GLAL cohort. And the way that we ensure 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 maralixibat 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 ALT, bilirubin, AHT, 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 maralixibat treatment group. And I think also important to note that SBA is not commonly collected in the real world. So that 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 GALA cohort looking at transplant-free survival and also pruning analyses to adjust for intermodal time bias. So taking all of this together, the pre-specified analyses that I just mentioned is 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 will hand it to Peter. Did you have another question for me?

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

Okay. I appreciate it.

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 that you can discuss of the data where either liver transplantation or biliary diversion surgery or decompensation events, perhaps patients are those that could have a greater benefit over others with LIVMARLI is?

Yes. So I think there's a really, we had another late-breaker presentation which was a poster and first author Dr. Ron Sokol. This really goes hand-in-hand nicely with the GALA natural history comparison and shows predictors of eventual. So we looked at our data and try to identify what are the predictors of entree survival and-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 transplant-free survival where 88% of patients who had that improvement remained event-free and transplant free.

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

Thanks for the question.

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

Hi everybody. This is Ryan Deschner, on for Steve Seedhosue. 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.

Yes. 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. So randomized, placebo-controlled data for all PFIC subtypes included in the study that we will be able to report on.

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

I think sort of follow-up on that, I will pass it over to Pam to share some of what we have 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 the study that we will continue to gather some of that data on.

Yes. Thanks. So yes, happy to speak about this for a second. So in our INDIGO Phase II study, we have presented data on patients who have 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 NAPPED, which is the natural history registry for PFIC. And when we applied those serum bile acid threshold 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 as was ALT, AST and peak quality of life. And of course and also pruritus, of course. So across, you see this broad-based improvement in clinical parameters, including growth as you are sitting in patients who have serum bile acid control. And so we presented five years of data on this. As Chris said, we will continue to look at the MARCH-PFIC 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 PFIC subtypes on this.

Okay. Thank you very much.

Thanks for the question.

[Operator Instructions].

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

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

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.

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