Hello, everyone and welcome to the Mirum Pharmaceuticals, Inc. Second Quarter 2021 Business Update. My name is Simona and I will be your coordinator today. [Operator Instructions] I will now hand you over to your host, Ian Clements, Chief Financial Officer to begin. Ian, please go ahead..

Thanks, Simona and good afternoon everyone. I’d like to welcome you to Mirum Pharmaceuticals second quarter 2021 conference call. I am joined today by our President and CEO, Chris Peetz and our Chief Operating Officer, Peter Radovich.

Earlier this afternoon, Mirum issued a news release announcing the company’s results for the quarter ended June 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 Mirum and that program is based on management’s current expectations, including statements regarding Mirum’s business plans, development programs, strategies, prospects, commercialization and market opportunities, financial forecasts and guidance, anticipated FDA interactions or announcements and certain other business matters.

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 June 30, 2021, and any subsequent reports filed with the SEC.

All statements are made as of today August 5, 2021 and are based on information currently available to us, and Mirum does not undertake any obligation to update publicly any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law.

With that said, I’d like to turn the call over to Chris Peetz.

Chris?.

Thanks, Ian. Good morning or good afternoon to everyone. Thanks for bearing with our technical difficulties getting kicked off. With our PDUFA date of September 29 for maralixibat, our focus is squarely on the realization of this upcoming potential launch.

Alagille syndrome is the leading genetic cause of pediatric liver transplant, many of these driven by the severe pruritus and systematic burden of disease. And these patients are waiting for new treatment options.

We estimate that Alagille syndrome alone may be a more than $500 million opportunity for maralixibat, and we are launch-ready and now have assembled the team and financial resources for successful commercialization, all while expanding our pipeline of potentially registrational studies in other rare liver diseases.

Mirum is focused on advancing life-changing medicines. Today, we will recap and provide context around some of our most exciting recent steps as we continue to realize our vision of being the leading rare liver disease company.

I will cover our regulatory and pipeline updates as well as the additional value we continue to build within Mirum’s clinical programs. Peter will share updates on commercialization and Ian will summarize our financial highlights.

With our PDUFA date for maralixibat in cholestatic pruritus associated with Alagille syndrome next month, our team is ready to launch upon a potential approval. Our regulatory review remains on track, and we’ve been able to accommodate all inspections to date, and the FDA has continued to indicate no plans for an advisory committee.

If approved in the U.S., maralixibat would serve as the first treatment approved for patients with Alagille syndrome. In the ICONIC study, which served as our pivotal study, highly significant improvements in pruritus were observed with more than 80% of participants achieving a 1 point reduction in score.

We have 6 years of follow-up data and see durable responses in trial participants across the extensions of all 3 randomized studies of maralixibat in Alagille syndrome. An approval and subsequent commercial launch would mark an important milestone for Mirum and more critically, an important milestone for patients living with this terrible disease.

We remain committed to further building on the body of evidence supporting maralixibat potential in Alagille syndrome. In June, we presented an integrated safety analysis of maralixibat in patients with alagille syndrome at the EASL Congress.

These data resulted from 5 years of maralixibat treatment across 86 patients and continues to reinforce our understanding of the drug’s safety and tolerability profile in patients with alagille syndrome.

Maralixibat was well tolerated in these patients for more than 5 years with the most common treatment-emergent adverse events reported in diarrhea and abdominal pain. In ICONIC, diarrhea incidence was at similar rates between maralixibat and placebo during the placebo-controlled portion of the study.

Also in June, we presented maralixibat transplant-free survival data for progressive familial intrahepatic cholestasis Type 2 or PFIC2 at the World Congress of Pediatric Gastonerology, Hepatology and Nutrition Annual Meeting.

As detailed in our presentation, maralixibat treated patients who achieved 75% serum bile acid reductions were shown to have 100% 5-year native liver survival. These PFIC2 data are under review with the European Medicines Agency.

Building on that, our Phase 3 MARCH-PFIC study continues to advance well, with greater than 65 patients randomized with PFIC subtypes 1, 2, 3 and 4 across two cohorts. As a reminder, MARCH-PFIC evaluates a higher dose of maralixibat and has been shown to drive greater bile acid serum.

We plan to extend enrollment and expect top line data in the second quarter of 2022. Further broadening our efforts in pediatric liver disease, our Phase 2b EMBARK study evaluating maralixibat and biliary atresia is progressing nicely as well, and we anticipate top line data in 2023.

In adult liver disease, we are excited about advancing our clinical programs for volixibat, which we believe is another potentially transformative treatment for several cholestatic liver diseases.

Earlier this year, we launched a Phase 2b VISTAS study for adults with primary sclerosing cholangitis and the Phase 2b OHANA study that will evaluate volixibat in intrahepatic cholestasis of pregnancy. A Phase 2b study in primary biliary cholangitis is targeted for later this year.

We have incorporated regulatory feedback into the design of these volixibat studies, all of which are potentially registrational. We expect interim analyses for the VISTAS and OHANA studies to occur next year.

And before handing off to Peter to discuss launch readiness, I want to touch on Mirum’s commitment to ensuring broad global access to maralixibat for alagille syndrome patients.

To facilitate the international reach of maralixibat, we recently entered into an exclusive licensing agreement with GC Pharma to develop and commercialize maralixibat in South Korea. This builds on our partnership with Cambridge Pharmaceuticals in Greater China, which we announced in April.

Both GC Pharma and Cambridge are leaders in rare disease and share our passion to advance life-changing medicines and we will pursue expedited approval pathways for maralixibat for Alagille syndrome based on our U.S. filing package.

We see the high interest level of our partners as testament to the potential of maralixibat for pediatric cholestasis patients. On that note, I will turn it over to Peter, who will provide an overview of our launch readiness activities.

Peter?.

disease awareness and patient finding; patient services and market access. Starting with disease awareness and patient finding, our field sales team has hired, fully trained and has been in the field for more than 2 months. We have connected with all of our key 125 accounts, including in-depth personalized discussions with the majority.

The team is providing disease awareness education on alagille syndrome and including recognizing full impact and severity of pruritus. We are gaining valuable account profiling insights from these discussions, including working with healthcare professionals to identify patients with alagille syndrome.

Additionally, as part of our patient identification efforts, Mirum participates in an industry collaboration genetic testing program, which provides free genetic testing and identifies mutations in JAG1 and Notch2, which cause alagille syndrome.

Together with what we’ve learned in our field discussions as well as the genetic testing program, our clinical research and expanded access programs also support our estimates that there are 2,000 to 2,500 children with alagille syndrome in the United States.

We continue to work with healthcare professionals to identify patients as we approach the potential launch of maralaixibat. Turning to Patient Services, Mirum Access Plus or MAP, which is Mirum’s program to provide end-to-end support for alagille syndrome patients and caregivers initiating maralixibat upon potential approval, is ready to go.

The MAP team has been staffed and trained. Full operational readiness will occur in the coming days in order to start preparing EAP patients to transition to commercial product upon a potential FDA approval. Finally, regarding market access, the payer team has been very busy. We have conducted 53 engagements within our top accounts.

The team has been educating Medicaid and commercial payers on the burden of alagille syndrome in order to prepare them to conduct a timely and evidence-based reviews, and ultimately, access decisions upon potential approval. We’ve invested early on this front.

The burden of this disease is hard to overstate and the broader community is learning about this dynamic that cholestatic pruritus is a leading indication for transplant and surgery in alagille syndrome. Overall, payers have recognized the devastating impact of alagille syndrome and the high clinical impact of maralixibat.

We remain passionate about and confident in maralixibat and the profound impact we expected to have on the alagille syndrome community. I am thrilled about our progress to date and look forward to sharing more about our ongoing efforts with an update after our PDUFA date next month. I will now turn the call over to Ian to share financials.

Ian?.

Thanks Peter. A fulsome look at our quarterly financials is available in the press release distributed earlier this afternoon and in the Form 10-Q. You can find both on 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 second quarter of 2021, all of which position us well to support the launch of maralixibat in two geographies and advise our development pipeline for both maralixibat and volixibat in their respective indications. Mirum remains well funded.

And at the close of the second quarter ended June 30, 2021, we had cash, cash equivalents and investments of $238.8 million. And also, as a reminder, we have access of up to a further $85 million from Oberland Capital.

This figure comprises $35 million upon approval of our NDA of maralixibat for pruritus in alagille syndrome and a further $50 million for mutually agreed upon in-licensing or acquisition opportunities.

Additionally, we anticipate receiving a priority review voucher or PRV in connection with our expected FDA approval of maralixibat later this year that may provide a further source of funds. With respect to operating expenses, for the quarter ended June 30, 2021, our G&A expenses were $13.4 million.

This amount reflects increased activity around launch readiness, including market research, disease state awareness activities and increased personnel costs to support our planned launches. Second, R&D expenses were $35 million compared to $18.6 million for the second quarter of 2020.

The increase here was primarily driven by an upfront payment and funding associated with the Vivet gene therapy programs and with the costs associated with initiation of volixibat clinical studies.

As Chris alluded to, part of our strategy at Mirum is to accelerate commercial launch and patient access globally through partnerships outside of our core U.S. and EU territories. On April 29, 2021, we announced our licensing agreements with Cambridge Pharmaceuticals.

Under the terms of this agreement, in exchange for an $11 million upfront payment, R&D funding and up to a further $109 million for future regulatory and commercial milestones, Cambridge has obtained the exclusive rights to develop and commercialize maralixibat within the Greater China regions for alagille or syndrome, PFIC and biliary atresia.

We can expect double-digit tiered royalties based on future product net sales. Additionally, subsequent to quarter end, we entered into an exclusive licensing agreement with GC Pharma.

Under the terms of this agreement, GC Pharma has obtained the exclusive right to develop and commercialize maralixibat within South Korea for alagille syndrome, PFIC and biliary atresia.

We received a $5 million upfront payment and were entitled to further research and development funding and up to $23 million for the achievement of future regulatory and commercial maralixibat milestones with double-digit tiered royalties based on product net sales.

So, as a result of strategic investments and experienced team and focused rare disease business model, we continue to have a robust balance sheet with access to approximately $400 million in capital, comprised of our cash position, the potential PRV monetization and strategic partnerships, we expect to be able to sustain our operations for the next 3 years.

With that, I will turn the call over to Chris for final comments.

Chris?.

Thanks, Ian. And thanks again, everyone, who joined the call today.

To close, Mirum continues to pave the way for the treatment of rare liver diseases with the potential FDA approval for the first-ever medicine for cholestatic pruritus and alagille syndrome and our other clinical programs continuing to progress across a wide range of indications, we are well on our way to realizing the company’s vision set forth 2.5 years ago.

To briefly recap our upcoming milestones. Our PDUFA date is September 29 for maralixibat in the treatment of cholestatic pruritus in patients with alagille syndrom. Upon potential approval, U.S. commercial launch will follow, and we estimate this to be a greater than $500 million opportunity.

We have upcoming key data updates on the pediatric program with long-term liver-related outcomes analyses in maralixibat treated patients with alagille syndrome, targeting upcoming medical congresses for presentation and top line data of the MARCH-PFIC Phase 3 study of maralixibat in PFIC in Q2 next year.

Potential international regulatory events ahead include the PFIC2 MAA under review with EMA, subsequent filings for Alagille syndrome in Europe and potential for partner market approvals.

Finally, our registrational program for volixibat in adult cholestasis has taken shape with interim analyses next year of the OHANA and VISTAS studies in intrahepatic cholestasis of pregnancy and primary sclerosing cholangitis. Lastly, initiation of the Phase 2b study in primary biliary cholangitis still to come this year.

We take pride in the meaningful scientific advances we have achieved so far and our ongoing engagements with the rare liver disease patient community as we continue to execute and maintain a strong cash position.

We are confident in our ability to achieve the milestones we have set from Mirum and look forward to the potentially transformative impact, maralixibat and volixibat could have on the lives of patients and their families. Thank you again for joining us.

Operator, could you please now open the line for questions?.

Thank you, Chris. [Operator Instructions] Our first question is from Mani Foroohar of SVB Leerink. Mari, your line is open. Please proceed with your question..

Good afternoon. This is Greco on for Mani. Thanks so much taking my question. I am hoping you could bridge us through the early period and look about launch in Alagille.

How should we think about timing of Medicaid reimbursement in terms of translating new prescription patient volumes into revenue for Medicaid patients for the upcoming launch?.

Hi Greco. Thank you for the question. Actually, I will turn to Peter to talk through some of our efforts on that front and how to think about the months and quarters ahead..

Sure. Thanks for the question. And as we mentioned in our comments, our payer team is out now actively engaging with these accounts with the goal of kind of facilitating timely reviews upon a potential approval. You referenced the Medicaid system specifically. So, manufacturers do need to contract with HHS for a rebate agreement.

And if the timing for the maralixibat approval comes around the PDUFA date, we would expect access and availability to participate in Medicaid program to open up early next year.

And then I think the other point is on the commercial side, there is a lot of different plans out there, kind of a heterogeneity of practices around coverage decisions and how those are made and when those are made, including some that will have NDC blocks for any new medicine and the specialty medicine off the bat.

So, I think the headline point is Medicaid will be probably a quarter delay. And on the commercial side, it will be heterogeneous with variable delays..

Got it. Great. I appreciate the comment and thanks for taking my question..

Thanks..

Our next question is from Yasmeen Rahimi of Piper Sandler. Yasmeen, your line is open. Please go ahead..

Thank you. Thank you so much for taking my questions. A number of them for you. Maybe the first place to start would be, how should we be thinking about what are key tech items for payers? We recently received some pricing detail for another IBAT inhibitor approved for the treatment of PFIC.

So, do you think that pricing could be competitive between PFIC and alagille? And then the second question is, what is the likelihood of potentially being able to have this fix-tier event-free survival analysis to be part of that label? And then I have one more follow-up..

Great. Thanks for the question. I will touch on a couple of those points and then turn it over to Peter to talk a little bit about what we do on the patient side to support access. From a starting point, alagille syndrome and PFIC are different indications.

As we think about our pricing decision and the value that we see in our long-term data and the profound impact of maralixibat in our pivotal study, that’s how we are going to be basing some of our pricing decisions as we head into them.

And on that long-term data on being able to look at kind of long-term outcomes from an event-free survival analysis in alagille syndrome, that’s what we are doing now. So, it has not been part of the FDA conversation. We wouldn’t expect that to be part of the label.

Our conversation with FDA is based on what we have set out from the outset in a pre-IND discussion with them, which is around the impact on pruritus in these patients where pruritus drives many of the liver transplant decisions. So, that’s what we expect to be in an eventual potential label.

Now maybe I will turn it over to Peter to give a little color on what this looks like on the patient side, some of the things that we can do to support access and patient navigation efforts..

Thanks, Chris. Yes, our Mirum Access Plus or MAP program will really be the central nervous system for this, both for the patient and caregiver, navigating logistical or financial out-of-pocket kind of implications depending on that particular patient’s insurance status as well as collaborating with healthcare professionals.

I think the expectation that we largely have and we see with other specialty medicines as payer practices ultimately kind of PA to label, kind of an approach or a prior authorization to label, so really evidence-based approaches to access to new medicines..

Thank you. Maybe two quick follow-ups, can you maybe highlight given the work that you guys have done with 125 accounts? What percentage of the addressable market out of the 2,000 to 2,500 patients in the U.S. could become eligible right away within the first year of launch? And then the second question I have is on the timing of MARCH-PFIC.

Are you able to comment on how – what percentage of total enrollment has been achieved at this point? And thank you so much for taking my long question..

No problem. Thanks for the question, as always. I will start with the finish and then hand it back over to Peter to talk about some of the account dynamics in patient finding. But on MARCH-PFIC, so as I said in the prepared remarks, over 65 patients randomized. That study can go up to 90, but is not needed to go up to 90.

So, we are looking at the balance across the PFIC subtypes, trying to hit a target distribution that we are getting quite close to some of the color I can give on the dynamic there, so over 65 and getting close to the completion. Peter, do you want to speak to the account and patient funding dynamic..

Sure. Happy to provide a little bit of color there.

So, as I mentioned, our field team has been out there profiling those 125 accounts for over two months now, and certainly finding patients and ultimately, we are kind of confident in the estimates we have put out there in terms of total number of patients based on those interactions among other data points.

I think your specific question was about how many of them would be kind of initial candidates.

I think the – what we see and this is probably not uncommon in any genetic disease is phenotypic variability in the presentation and probably approximately half of the patients with alagille syndrome have pretty severe disease and are really kind of refractory to the available off-label therapies that are out there today.

So, I would kind of think of that as an initial kind of place that’s probably a logical place to start. I think, in terms of utilization, but ultimately, building out over time, we are confident that maralixibat can address the full population..

Thank you..

Thank you, Yasmeen. Our next question is from Ed Arce of H.C. Wainwright. Ed, your line is open. Please proceed with your question..

Hi. Good afternoon everyone. This is Thomas Yip asking a couple of questions for Ed. So first, regarding PFIC2 in Europe, you mentioned that M&A decision is anticipated there early next year.

Can you talk briefly about the progress of commercial prep there, any specific countries or every year is the focus that you have in mind for now?.

Yes. Thanks Thomas for the question. Actually, I will turn it to Peter to talk about that. He will give you the color – a little color on how we think about it globally about the various markets and what we are doing to get ready for approvals..

Thanks for the question. We have built an international team that covers Europe and really all ex-U.S. territories.

Within Europe, we are planning direct commercialization in kind of Central Europe and Western Europe is really our footprint and really focused on the big five initially and have built out a commercial and medical affairs team, among others, the G&A support team there and really focused on launch at key stakeholder engagement in that region.

And then as Chris alluded to, we are also very active looking in markets with partners. I think we talked about in our prepared remarks, South Korea and China, where there is an opportunity for expedited regulatory pathways based on the U.S.

potential approval as well as other geographies where it’s possible to reach those markets in a relatively effective timeline and also favorable market access. So, where Europe is certainly part of the international expansion plan, but we think there is a lot of opportunity even outside of Europe..

Thanks for the additional details. I perhaps still on PFIC for the Phase 3 study data that’s coming in second quarter of next year. Do you guys have any progress with the FDA specifically regarding what specifically they are looking for, for PFIC approval in the U.S.

or have we been holding patent until we see the data?.

Yes, thanks for the question. So, the MARCH-PFIC study was extensively discussed with FDA. So, we have worked everything into that study to address what they are looking for.

So of course, we have to get to the results, but we feel confident that with the dose of maralixibat in that study, we should see improvements on the activity levels that we saw in the Phase 2 Indigo study and looking forward to that readout in the second quarter..

That sounds good. Perhaps one last question, this one for Ian, we went over major components of the U.S. launch preps for alagille syndrome.

Can you tell us really rough ballpark costs of each major component, so headcount and marketing and the patient access programs?.

Yes. Thanks, Thomas. We haven’t given specific kind of guidance around the kind of the breakdown. But as you think about the numbers of people and activities involved the whole of our operating expenses, it’s a fairly small number.

Considering if you think about sales force, for example, we have got ten reps across the two managers, MSL teams, about five people across the U.S., so a very compact and efficient model in terms of the commercialization stand from that perspective..

Okay. That sounds good. Thanks again for taking my questions and we look forward to the update in September..

Thanks Thomas..

Our next question is from Steven Seedhouse of Raymond James. Steven, your line is open. Please go ahead..

Again. This is Ryan Deschner on for Steve Seedhouse.

I wanted to ask, the decision to submit the MAA for ALGS based on, only on the ICONIC fixture event-free survival data or is there new additional long-term FDA pruritus data in there?.

Hi. Thanks for the question.

So the MAA package that we are working towards for alagille syndrome does include an expanded data set and so going back to some of the early conversations with MAA about alagille syndrome and about PFIC as well, frankly, in these programs, as they had asked for incorporating and looking at long-term outcomes in any submission.

And so what we have been looking at with the alagille syndrome package is in addition to ICONIC, which serves as a pivotal study and how we think about Europe similar to the way it is in the U.S. We are looking at supportive analyses on long-term event-free survival.

We also have a collaboration with the National History Effort looking at outcomes in the pooled alagille syndrome study. So, the three randomized Phase 2 studies and the open-label the follow-up that encompassed 86 children in total and the 6 years of follow-up.

Looking at that cohort of patients against a natural history control group and evaluating event-free survival. And that’s work that’s ongoing and will be part of the European package..

Okay. That’s helpful.

And then I also wanted to ask, as the Phase 2b embarked study for biliary atresia activated sites in China via the Cambridge collaboration and if some patients started enrolling in China?.

Alright. That’s still to come. So, we are active in site start-up, but they are not opening quite yet. Similar, we will also look at Korea for sites working with GC Pharma..

Okay. And then finally, in terms of future market share in China, how different would you anticipate market penetration to be across alagille and biliary atresia versus in the U.S.

market?.

It’s actually there – it’s hard to really characterize that without kind of bringing Cambridge into the conversation, frankly. There are some country-specific launch dynamics that as they get kicked off. I don’t want to get ahead of speaking for them while they work on their launch plans and sequencing the indications..

Okay. Thank you very much..

Thanks for the questions..

Our next question comes from Brian Skorney of Baird Capital. Brian, your line is open. Please go ahead..

This is Luke on for Brian. I was hoping to get a little more color on the volixibat readouts expected next year.

Can you talk a little more about the pace of enrollment and what you are thinking for the advocacy for our studies?.

Yes, absolutely. Thanks for the question. And so the two studies that we expect interims for next year are the OHANA study in cholestasis of pregnancy and the VISTAS study in PSC. These are both adaptive design Phase 2b studies. So, in the first portion of each of these, they are looking at both 80 milligrams and 20 milligrams BID against placebo.

So, that’s one of the first focuses of the interim analysis in each of these is to look at dose selection and to be able to consolidate those. So, we will be looking at comparative efficacy and serum bile acid movements between the two dose levels of volixibat versus placebo as we make that dose decision.

And for the ICP study for OHANA, there is a unique feature to that study of design that’s forth mentioned. In addition to the formal blinded placebo-controlled portion of the study, there is an open-label cohort of milder ICP patients.

And that will give us our first interim from that study and get an early sense of activity level on serum bile acids and itch will be the – a couple of things to look at in that open-label data.

So really, we have designed these programs to be adaptive in a very strategic way so that we can have these roll into potentially registrational portions of the study after these interim time points. So, the interim analyses will guide that dose selection and sizing of the second portion of the dose..

Thank you..

Thanks for the question..

[Operator Instructions] Our next question is from Etzer Darout of Guggenheim Partners. Etzer, your line is open. Please proceed..

Great. Thanks for taking my question. Just a couple for me.

Just firstly, just wanted to maybe get your comments on any meaningful takeaways from the competitor PFIC label as you sort of think about sort of post MARCH-PFIC next year and as it pertains to conversations with regulators? And secondly, sort of understand that the biliary atresia, the cause of – underlying cause of that disease is not well understood.

But just wondered your thoughts around sort of how de-risking ALGS PFIC data sets in general could be as we kind of think about the biliary atresia readout then in 2023?.

Yes. Thanks for the question. So, first comment on the recent approval on PFIC. It’s just great to see, great to see a product approved and it’s really terrible indication.

And I think from a high level, what we saw there was really in line with expectations based on what we have learned from FDA’s viewpoints on looking at pruritus as an approval endpoint in a setting like this, and how it all ties into the transplant dynamic, and it’s just a terrible component of this disease.

So, we see that as a great progress point for the space and how we think about our program as well. Moving to the biliary atresia point, that is a very different disease than alagille syndrome and PFIC because it’s not only the heterogeneity, but also just the physical biology in a post-Kasai setting is different. It’s a different disease.

And which is why we are approaching it in a different way with the EMBARK study, looking at six-month bilirubin, serum bile acids, those two serum markers being the most looked at and predictive prognostic markers and looking at transplant survival and some of the recent analyses that have been presented at scientific congresses.

So, looking to get a read in a relatively quick timeframe on what the potential impact of maralixibat is in these quite sick children..

Great. Thank you..

Thank you, Etzer. We currently have no further questions. So I will hand you back over to Chris..

Great. Thank you, and thanks for joining the call today and for your interest in Mirum. We are excited about the events ahead of us in patients suffering from alagille syndrome are waiting for new treatment options, and we look forward to providing an update after the upcoming PDUFA date. Thank you so much..

This concludes today call Thank you all for joining. Have a great rest of your day. You may now disconnect your lines..