Mirum Pharmaceuticals, Inc. (MIRM) September 2026 Conference Transcript

All right. Hello, everyone, and thanks for joining us at the Morgan Stanley Global Healthcare Conference. I'm Mike Oltz, one of the biotech analysts here. It's my pleasure to introduce Chris Peetz, CEO from Miram Pharmaceuticals. Just as a quick reminder, the format for today is a fireside chat, but if anyone in the audience has a question, you can raise your hand, and we'll try and address it in our discussion here. But before we get started, I just need to read a quick disclosure. For important disclosures, please see the Morgan Stanley Research Disclosure website. at www.morganstanley.com backslash research disclosures. And if you have any questions, please reach out to your Morgan Stanley sales representative. And with that, Chris, thanks for sharing your time with us today. And maybe I'll just hand it over to you to make some introductory comments.

Yeah, thanks for hosting. Great to be here. And I'll make a quick disclaimer on my end as well. I'll be making forward-looking statements so I'll refer you to the SEC filings for Miriam for a more complete risk factor disclosure. and a bit about Miram we are a company that's established just under 8 years ago and focused on pulling together high impact medicines for rare disease that are often overlooked, missed by some of the bigger companies but really compelling opportunities not only from patient impact but also as a business model and pulling these together in an efficient this year we're on track for $680 to $700 million of revenue across three approved medicines, really had a kind of emerging growth trend, and one of our indications in particular with PFIC that I'm sure we'll spend some time talking about, and a pipeline that is very busy right now. So later this quarter, later this month, actually, expecting to announce the top-line data of the Azure I Phase III study of Brilovatug and Hepatitis Delta. We have a PDUFA date from one of our newly added programs in FOP. More readouts, two more Phase 3s reading out next quarter, and another study in PBC first quarter next year. All this on the back of entering into a regulatory conversation for PSC for Flixbat as well. So it's a busy stretch for Mirum. And kind of on the other side of this, see a real inflection on business performance from all of these data readouts and launches that we expect in the near term. So exciting time across the board.

Thanks for that introduction. Yeah, lots to get through here. So maybe we just start with the commercial business and Livmarly, and you touched on this in your prepared remarks, but you're seeing some nice sort of growth in PFIC. So maybe talk about, you know, what you're seeing there and how you think about that going forward.

Livmarly is approved in two different indications, cholestatic pyritis due to Allergyle syndrome and cholestatic pyritis due to PFIC. And first approval in Allergyle syndrome continues to be a growth driver, so we, across the board, continue to see new patient starts. The response profile for most patients is quite meaningful and see strong compliance and persistence as well. So that plays well for the brand over time, both this is U.S. as well as international performance. The PFIC indication was added subsequent to the Allergyle syndrome launch, and it's been an interesting story over time. Initially, we saw this as a pediatric opportunity. That's what our field team was primarily targeting in finding the pediatric profile of a PFIC patient. As we've been in market with Livmarly in puritis due to PFIC, substantial underdiagnosed population in adults that actually have PFIC and have to date been labeled as idiopathic cholestasis. So really just an incomplete diagnosis in many of these adult cholestatic patients with puritis. And that's something that we've seen start to contribute to the top line over the past year. A very durable trend in everything we're seeing. In fact, we're now in the process of expanding the field commercial team to help support some of that patient finding and diagnosis, help build awareness of availability of it for adult patients. We estimate there's probably about 2,000 adult PFIC patients in the addressable market that are out there in the U.S., so that's kind of one of the near-term drivers for the continued growth on the commercial business.

Yep. As we look, you know, next year and beyond, you also have a phase three expand study ongoing that could even, you know, further expand the opportunity there. So maybe just talk a little bit about that, maybe give a little bit of background, how you ended up sort of targeting that indication and what to expect when we see data, I think, in the fourth queue, fourth quarter.

Yeah, like Marley as a whole, we see it as a billion-plus brand opportunity driven by all these different components, Expand being a substantial contributor to it as well. It is a basket study, so it's a collection of causes of cholestatic puritis that by definition in our discussion with FDA are too small to run a standalone study in. So a good number of them in the study are biliary atresia. That's probably the only one that's a little bit more common of the mix. And then very small numbers of other genetic and non-genetic causes of cholestasis that end up with a puritis presentation. The study looks at both pediatric and adult patients. The readout, the primary endpoint that we're expecting next quarter is in a pediatric cohort. That's what the study was primarily powered and designed around. So expect to see that as the top line next quarter, the pediatric patients, with an identified subset looking at biliary atresia as well as a secondary because it is about half of the patient population. There's probably 500 pediatric patients in the U.S. that make up the addressable market that we've identified in size. It's an early estimate. It's hard to tell how big of an indication this could be in adult settings as well. There are some adult patients out there, certainly. We just don't know quite how many. So it's a nice add-on to what we're already seeing in algeal syndrome and PFIC.

Can you talk about what drives your confidence in being successful there? You know, any prior data you can point to?

Yeah, really the genesis of the study design came from physician interests and compassionate use case studies. So we do have, not in a clinical trial format, but we do have anecdotal case study evidence seeing response in a number of these types of settings. Biliary atresia in particular, we've presented some of the case studies of a series of biliary atresia patients with cholestatic pruritus being treated, and it's what you'd expect for an IBAT treatment. In a patient with cholestasis, elevated bile acids, and itch, you can expect to see a nice response in the clinical data that comes out from those studies.

Great. And if we just sort of stick with the commercial portfolio and specifically the bile acid portfolio, you added that a couple years ago, and it seems to be performing well, so maybe just talk a little bit about that, what's driving that and the outlook there.

The bile acids Cetexaly and Coldom have grown nicely with a dedicated team behind it. One of the things to note when we brought those products in, a realization we had is that the prescriber universe is not entirely hepatitis. Many of these patients, in particular for Cetexaly, and for some of the Kohlbaum indications are in medical genetics or neurology. It's more of a patient finding and diagnosis effort that doesn't exclusively happen in hepatology. So we built a separate team that focuses on those other settings and the patient finding, and they've done a fantastic job over time with these products. And it's about having a dedicated effort that is a different strategy than what the liver team is doing. so it makes sense to have a different team staffed against it. And actually, it fits really well with one of the things to come on FOP. That's the team that's going to be launching Zolderga Certib and FOP, and it's a really similar effort, overlapping call points in terms of the institutions that these people are visiting and in contact with, and a similar effort in terms of following data on a diagnosis and, you know, leveraging some of the referral patterns that happen for these ultra-rare conditions like FOP, like CTX.

Maybe talk a little bit more about FOP and kind of what attracted you to that asset and, you know, kind of what drove that.

Somewhat from kind of what I was just talking about with our expansion into medical genetics and kind of thinking of rare disease as a therapeutic area, We've been looking for other kind of team and call points to put more in the hands of this team that's been executing. So looking into FOP and the programs being run there, the biology and the data are striking. So this program, Insight, did all the work on the Phase II study that supported the NDA submission, compelling data that's come out of that, showing that you can really, versus placebo, in the volume of ossifications that build up over time for these patients, groundbreaking data for FOP patients, to be able to halt that formation of new ossifications and dramatically change the course compared to placebo in those data sets. So both that clinical data and how clear it is, as well as the fit with our team and business model, comes together in a great story. And, you know, the conversation, you know, focused between two companies, right? This was something that didn't fit with their business model. It's clearly aligned with what we're trying to do. So it was a natural transition that we set up.

Yeah, makes sense. With the PDUFA date coming up here, can you just talk about launch preparations? Can you hit the ground running? It sounds like you probably can, but maybe just talk a little bit about that.

Yeah, and then for launch preparations, field team, It's the same team that's already out there for the bioacid medicines in terms of the staffing, largely, that's all in place. And so we're ready for the Hadoofa date and decision in a couple weeks. That's the point that triggers a transition of sponsorship from Insight, so a couple of steps there to get this launched in Q4.

Okay, great. Since we've been sort of on the topic of BD, You know, you've obviously been pretty active over the past few years. So maybe just talk, you know, more broadly about your BD strategy, you know, your thoughts currently. You know, are you looking to add more programs or do you have enough catalysts over the next six months?

Well, I'm a little, we're a little busy for the next six months. But it takes time for these deals to come together, which I think is, I mean, that's behind the overall strategy for Miriam, how we got to where we are today. and the vision for the path forward is to always be active, to find the opportunity that is compelling both from the biology, data, and patient impact, but then also that fits with the mirror and business model, that you can have an intersection where the deal economics work for both sides. It takes time and being a little bit opportunistic. On the BD front, we're always active looking at things. You know, the range of things that could be of interest remains the same. You know, phase two opportunities of interest and could fit well. But granted, the next six months are a little packed. So, you know, adding a phase two sounds like a pretty good idea to me instead of another launch next year. Yep, understood.

And I guess what areas of focus, is it like rare genetic liver? Could you go outside that at all, or does that make sense for you?

We look outside of liver and outside of the broader current therapeutic areas where we're active, because we see rare disease as the therapeutic area, as the expertise that we bring. So the ability to commercialize medicines where they are maybe harder to diagnose, harder to get to a point of care where it's maybe a first product in class or in the indication kind of setting and changing a standard of care these are the types of opportunities that our team has shown that they can execute on and so it's not so much tied to the model around a rare disease product launch and we're seeing as we saw with the bile acid products how we're approaching the Zalurga Certib launch, you can leverage this into new therapeutic areas pretty easily. So adding on the endocrine call point and some of these tertiary centers for what we call the GEM team.

We can keep it rolling, moving to Velixabat, and may we just start with PSC and just maybe talk a little bit about the market opportunity there and the unmet need and how you see it.

So backdrop of PSC as an indication, this is an autoimmune-driven cholestatic condition. It presents most commonly in adults, but there is a pediatric onset form of it as well, and the hallmark of it being the fibrotic strictures forming around the bile ducts, leading to progressive liver complications. It's also associated with frequent episodes of cholangitis. highly variable liver labs, and just really a very difficult setting to treat clinically. And it's been very tough for drug developers historically. So we've seen a number of programs early on exploring different endpoints, using histology, using different biomarkers. None of those have really panned out. When we approached it with Velixivet, but leveraging some of what we learned on the pediatric side, using the symptomatic burden as the endpoint for our registration program, and clear that pruritus is patients. That aligned well to be an endpoint in PSC, similar to how we've used that in allergial syndrome, PFIC, and PBC, so good precedent for how it's used in other settings. and with the NPSC for Velixabed, which I'm sure we'll talk about, kind of diving into it here, had that conversation with FDA, good, clear written correspondence discussing the study design, the registrational and substantial patient need endpoint and indication, and had good alignment on the study design and announced earlier this year offline data. So CLEAR presented at Easel this year, PURITIS, and the VISTA's study for Veloxabatin PSC.

You also shared that positive data with the FDA, and the FDA sort of requested phase three. So maybe just walk us through what happened there, and what are your thoughts on that going forward from here?

So working through the situation on the regulatory front now, it was a bit of a surprise for us. So, you know, after the positive readout, we were meeting with FDA and had the surprise recommendation from them to conduct a Phase III study, a surprise for us in many ways because we had alignment on the study from the start as a pivotal study. In the conversation, a lot of the different aspects of the program were discussed. All of them, you know, were present at the start of the program and were considered with the original study design. So we're a bit surprised by the reaction. Subsequent to that meeting, we were granted breakthrough designation. So we're using that as an ability to have a bit more access. And so over the balance of the year, planning to have interactions with the FDA through written submissions, sharing more of the VISTA's data with them. Admittedly, we have not submitted full data sets to them yet. So I think there's a lot to be gained from getting them closer to some of the data sets that answer a lot of the questions on treatment in this patient population specifically, and even get to a live meeting potentially. And all this with the goal of submitting our NDA in the first half of next year. So absolutely still the plan to submit an NDA for Elixabed and cholestatic prurides due to PSC based on VISTAs first half of next year. the strategy between now and then is to build familiarity with the robustness of the data set and kind of bring the review team closer to kind of how we're seeing things before we get to that.

Walk us through some of the potential scenarios there. Are you pretty confident that you'll be able to file on existing data or are there other data you could use? You know, maybe what are some of those potential outcomes, I guess?

Well, in the interaction with FDA, it was made clear that we can submit at our election. and something put on the table to prevent us from submitting an NDA. So there's a recommendation from them to run a Phase III study. We think the points brought up in the meeting really can be addressed by the current study. And frankly, we don't know what new would be answered by an additional study. So scientifically, we haven't heard something that needs to be answered that can't be answered in the VISTAs data set. And that's what's behind our strategy to, you know, take steps forward to bring the current data set to an NDA next year.

Maybe we can switch to PBC and maybe talk a little bit about, you know, the market opportunity there relative to PSC.

In PBC, we're also conducting a phase 2B study adaptive design with felixivate and cholestatic parietis due to PBC. We already presented interim data a couple of years ago from that study that showed a really striking improvement in pruritus versus placebo. In two doses of Elixabat, the adaptive design then took one dose forward for the confirmatory portion. That's the data we expect in the first quarter of next year. Granted, breakthrough designation. Have some more clarity on the regulatory front on that one from those interactions last year as well. And kind of tying this to the clinical setting, in PDC, it's a much larger indication in terms of just overall prevalence, probably 80,000 or more patients in the U.S. with PDC. And there are other medicines approved in PDC for different settings. So UDCA is standard of care. That's generally where patients start. There's a second-line setting for those that are not controlled biochemically on UDCA, so in other words, if they have elevated alkaline phosphatase levels, they'd be considered for a PPAR, which were recently approved. In the backdrop, symptomatic management is emerging with new tools available and becoming available, so there was recently an IBAT inhibitor approved for cholestatic pyritus and PVC. That's relevant across both first and second line PVC, just like we are developing Velixivet. So Velixivet is being studied in both first and second line PBC. In the interim analysis, both settings were represented in those patients, and you see a nice improvement in pruritus across both profiles. So I feel that we're on track to have potential medicine that can address symptomatic burden across all lines of therapy.

And you're going to share, I think, the Phase IIB registrational study in one queue, I guess. You shared some prior data. Is that like a good estimate of what the outcome might be or the reason to think the outcome might be a little bit different on the pruritus endpoint?

The best evidence we have is from that interim analysis of the Vantage study where we saw a 2.4-point placebo-adjusted difference. that frankly that's a really strong result compared to some of the other data sets out there anything around a two-point difference from placebo in pbc is getting getting close to that in the full data set would just and i guess your level of fda interaction on pbc and the risk that they may also want you to run a phase three study here what's the thinking there We've had the opportunity for more recent interaction with PVC. And one of the things that we've looked at is the division leadership has changed over the course of this program. So more recent interaction, I think, is quite relevant and helpful. We've gotten feedback from the current contemporary team that's in the division. And after the breakthrough designation, we were thinking about the ultimate study size for Vantage. We had some flexibility to potentially keep it smaller or upsize it. That was one of the decisions we wanted feedback on in the context of a pivotal study. So in written correspondence with FDA, we confirmed some questions on study design and on the analysis plan. So I feel like we have more recent input from them. And that's why the studies now ended up over 300 patients in total to align with what other PBC programs have had for their submission data sets. And even in these correspondence, we even have direct on, you know, if these studies are considered pivotal, these are the analysis steps that you should take. And we're able to accommodate all of them. So I feel like we're aligned on PBC.

Okay.

Great. and maybe we'll just keep moving here.

So for Lovatog, HDV, you have some Phase III data coming up soon, but maybe just to start, paint the picture for us, you know, why HDV, what was attractive, you know, for this program.

Yeah, so Hepatitis Delta is a Hep B. It's rare, so it's far less common than Hep B, but it is far more dangerous than progressive. So it is a highly progressive condition where these patients tend to progress to liver failure, liver cancer complications at a much faster rate than hep B alone. So the goal of treatment here are levels, so we're looking at HDV RNA response and improve long-term liver outcomes. And one of the ways that's measured in the studies is ALT normalization, part of the composite response. We think there's, we estimate there's 15,000 patients with hepatitis delta diagnosed in care. That's from insurance claims data, so also kind of in the insured population, estimate 15,000 patients. But it's likely very underdiagnosed. And guidelines for testing for hepatitis delta in hep B patients has been more of a risk-based. it's likely not even sufficiently doing it at that level. So a very low percentage of Hep B patients get tested for hepatitis Delta. So we think there's probably 40,000 patients that are in total in the prevalent population in the U.S. So a lot that can be done if we can help support changing some of the reflex testing that really should happen now that there are therapies emerging for hepatitis Delta. an interesting parallel in Europe, actually, where we've seen this play out, approval of hep Cludex about five years ago in Europe. You saw a shift in guidelines, and that did result in a meaningful change in the testing patterns, you know, from 10 to 20 percent of hep B patients being tested for delta now towards maybe as high as 90 percent. And the positivity rate on those tests hasn't changed, so they're capturing far more of these patients that would otherwise be undiagnosed and have a more progressive background disease.

In terms of the data, maybe just walk us through a little bit of, you know, what we've seen so far and kind of is that a good proxy again for the data coming up here?

The Berl-Ovita program has had some just really impressive response profile in the Phase 2A and Phase 2B data sets. there's two different studies that have read out. Phase 2a was a sequential dose exploration study looking at different doses and regimens, and that kind of gave the signal for what became the Azure Program 3 readout. The phase 2b portion of that, I think, is the most instructive data to look at. It's randomized control, two regimens of Vrlova Tug versus delayed treatment, looking at 300 weekly and 900 monthly and nice response across both regimens in particular the 300 weekly dosing looking quite strong where you're seeing 100% duologic response at only 24 weeks you're already getting a substantial proportion of these patients with ALT normalization and our program has no baseline ALT requirements so some of these patients are coming in with very high ALTs. So to get them to normal in that time frame is quite impressive from a response profile. And so that's kind of what we look to as the best guide for what to look for in the Phase 3 readout. A lot of overlapping sites from those first patients in 01 to kind of look at what's possible for the Phase 3 portion.

Makes sense. Can I also ask just about, you know, a competitor also is going to have Phase 3 data coming up, you know, later this year as well. So maybe just talk about key points of differentiation or how you position your product.

Yeah, I mean, the real, part of what got us so excited about BrlovaTug really, I think, will stand out as we get into a competitive launch. Yet another one. We've done, we tend to, we tend to like these situations. BrlovaTug is a fully human, I think that has some real advantages on the safety tolerability profile. In terms of what we see is very low injection site reactions or flu-like symptoms. I think that's going to shine commercially when we get out there. And the response profile at 24 weeks is good and appears like it's only going to improve over time. So that's another thing that we'll be looking to share data on as we go is some of the data updates as these phase 2b and eventually phase 3 patients get towards 48 weeks or 98 weeks. Single agent, fully human antibody, you can get the HDV RNA levels and get more and more patients to ALT normal.

Maybe in the last few minutes here, we just switched to just Fragile X syndrome. Maybe give us kind of the background there and kind of your latest thinking.

So the MRM3379 program for Fragile X is a PD4D inhibitor, and we're looking at trying to impact some of the cognitive scores and measures in fragile X patients in the dose-ranging Phase II study that we're running. Important to note, this study was based on a signal from a different Phase II program of a PD-4D inhibitor that had an interesting signal on cognitive scores. We've not seen that replicate in the Phase III study, so it does kind of call into question some of the strategy here. I will say that we're asking all the right questions. So in our Phase II program, we're doing a more complete dose ranging than was done in this competing program from what we've seen. And one of the things that excited us about 3379 as a program is that it has penetrance, so it was designed for CNS exposure. We've got the right profile for this setting, but we'll have to wait and see what comes out of the data next year. The study's enrolling well. It's a really engaged patient community and setting, so we'll have an update when we get to data next year.

Great. I think we covered it.

Yeah, I really appreciate the time. I think just to kind of come back on a closing thought, Miriam's at a real inflection point here. Commercial business on its own is already performing well with that $680 million to $700 million top line for the year. we're seeing that and expect it to really in the next couple years start to play through in an impressive way on a margin basis as we start to launch these additional products and build on the efficiency on what we've built here you know with the the liver team eventually having three products live marley for lova tugs elixabat a lot of reasons to to be kind of a leading thought partner for hepatology and gi and then on the the genetics and endocrine metabolic team having an exciting launch to work with there with a team that that knows how to get up get out there

and have an impact and help bring patients to therapy yeah a lot to look forward to so thanks so much chris really appreciate your time today yeah thanks for the time thanks for the interest