Mirum Pharmaceuticals at Leerink Conference: Growth in Rare Diseases

On Tuesday, 11 March 2025, Mirum Pharmaceuticals (NASDAQ: MIRM) participated in the Leerink’s Global Healthcare Conference 2025, where CEO Chris Pietz outlined the company’s strategic direction. The discussion highlighted Mirum’s robust growth prospects in the rare disease market, driven by their flagship product Livmarley, while also addressing competitive challenges and market dynamics.

Key Takeaways

• Mirum Pharmaceuticals projects revenue of $420 million to $435 million for the year.
• Livmarley is the primary growth driver, with expansions in Alagille syndrome and PFIC.
• The company aims to maintain financial independence and strong cash flow.
• International revenue may fluctuate due to tender orders.
• Expansion into new rare disease areas is planned through acquisitions or development.

Financial Results

• Revenue Guidance: Expected revenue for the year is between $420 million and $435 million, with Livmarley as the primary contributor.
• Commercial Margin: The cash commercial margin stands at about 50%, with expectations for growth.
• Financial Independence: Mirum is positioned to be financially independent and cash flow positive.

Operational Updates

• Livmarley: Continued expansion in Alagille syndrome in the U.S. and internationally, with new patient starts in PFIC and potential label expansion through the EXPAND study.
• Citexley: Focus on improving diagnosis and patient identification through dedicated sales teams.
• Alagille Syndrome Penetration: Approximately 40% penetration in the U.S. and Western Europe.
• Distributor Markets: Planned launches in Japan and Latin America through partnerships.

Future Outlook

• Livmarley Lifecycle: Expected to see healthy growth, supported by weight-based dosing and indication expansions.
• PSC Indication: Anticipated to be the first product for this indication, with enrollment completion on track for this year.
• Business Development: Actively seeking to expand the product portfolio and bring on clinical-stage programs.

Q&A Highlights

• Competition: Livmarley holds a pricing advantage in Alagille syndrome; growth in PFIC is ongoing.
• PBC Dynamics: Two-thirds of patients are on UDCA, with the unique valyxibat program enrolling across all settings.

For a more detailed discussion, refer to the full transcript below.

Full transcript - Leerink’s Global Healthcare Conference 2025:

Unidentified speaker, Host: Welcome back to, I guess, we’ll say the mid morning session of our second day of the twenty twenty five Global Healthcare Conference here in Miami. I’m very fortunate to have Chris Pietz, CEO of Miriam Pharmaceuticals. How was the trip out, Chris?

Chris Pietz, CEO, Miriam Pharmaceuticals: All good. Yes, thanks for hosting. It’s great to be here.

Unidentified speaker, Host: Always happy to host people in my adopted home. Let’s talk a little bit, we can dive right in to the growth rate implicit in your guidance. Just talk about the base business, level set where we are in terms of Limarley’s growth and penetration and then move down separately to sort of the growth the base growth right now in the acquired assets?

Chris Pietz, CEO, Miriam Pharmaceuticals: Sure. Yes. And first point out that I’ll be making forward looking statements. So refer to our SEC filings for a complete a more complete risk factor disclosure. But turning to the commercial side for Miriam, the commercial business is in really great shape, pointing towards $420,000,000 to $435,000,000 for the year.

That’s the $2,025,000,000 dollars guidance. And underneath that, see all brands growing and contributing to that growth rate. Starting with Liv Marley, continues to be a strong growth driver and is really the bigger contributor to the growth when you look at moving into 2025, driven by Alagille continued penetration in The U. S, a lot of international launches for Alagille syndrome expected this year. And then also the PFIC expansion that started last year continues.

And so we’re continuing to see nice new patient starts for PFIC contributing to Livmarly’s growth. Bile acid products will continue to kind of do what they’ve done. They’ve been steadily accumulating patients and growing over time. We just had the approval of Citexley for CTX. We see that as a way to help what we’ve been doing is to bend the curve a bit on that growth rate.

So the Citexley launch really is all about adding more patients through more active promotion, supporting diagnosis. So we’ll start to see some of that this year, but think of that as more of a gradual effect over time. So kind of putting it all together, I mean, the Liv Marley being the highlight of growth, one thing I’d point out is that, that profile for Liv Marley, we expect it to grow in a healthy manner throughout its lifecycle. There’s a lot of great tailwinds, not only on getting further into the established the current diagnosed patient population, but also you see a weight based dynamic weight based dosing dynamic for Lymph Marley that continues to contribute as well as further indication expansion, not only with PFIC, but also the EXPAND study being a third potential label expansion for LivMarley that we’re working on.

Unidentified speaker, Host: So let’s start a little bit with the Cetexley side. When you talk about bending the curve, operationally, sort of what are the metrics that you’re following to so that you can bend that curve? And what are the things you can do in operational terms to move that number?

Chris Pietz, CEO, Miriam Pharmaceuticals: Yes. A lot of it comes down to helping support diagnosis and awareness in some of the clinics where these patients present. So we’ve deployed a number of different programs that really support genetic testing, getting those into the different specialists that would see these patients when they present. So some of that will be in pediatric ophthalmology where bilateral cataracts can be a signal of CTX and a chance to potentially catch them earlier. And movement disorder clinics, having a panel of different genetic neurological conditions available, those are different programs that we’ve recently launched to help support diagnosis.

And then also, we have a dedicated sales team now that is focused on medical genetics and neurology. So in addition to the liver GI team, we do have a dedicated field team helping to support finding CTX patients. We do think that when they are when a patient is diagnosed, they’re very likely being prescribed. So this is really all about patient identification and helping to catch those patients earlier and prevent some of the irreversible consequences of the disease.

Unidentified speaker, Host: So let’s move from Cetaxly over to Lim Marley and talk a little about the depth of penetration into that market, U. S, EU, globally, like where are we in terms of the proportion of patients that are diagnosed out of the prevalent existing pool?

Chris Pietz, CEO, Miriam Pharmaceuticals: For The U. S. And Western Europe, so these are the markets where we’re commercializing directly, we think we’re probably about forty percent or so penetrated into the prevalent Algeois Syndrome population. And so kind of where we build from there is we do see the ability to penetrate further into that prevalent pool. And so we’re deploying on making that happen.

But also keep in mind that there are new diagnoses every year. So it’s a lot of catching these, the patients when they’re diagnosed typically in infancy to be a treatment option for them when they kind of start some of their disease management decisions early on. And then so beyond that kind of U. S, Western Europe profile, we’re still pretty early in a lot of these distributor markets. We’re commercializing through partners that have the kind of on the ground expertise in smaller markets and leveraging a lot of their work as they find access to different rare disease funds to get reimbursement.

So see more of those geographies potentially coming online this year. Call out Japan and Latin America are a couple areas that we’re looking forward to having launches coming up this year.

Unidentified speaker, Host: So from a purely stock perspective, how talking about how those distributor launches in new and some of those new economies, Latin America, Japan, etcetera, how will those flow through onto the income statement? Should we expect those to be chunkier? Should we expect them to show up sort of dribs and drabs over the course of the quarter? I know in some places, Brazil, for example, that tends to show up as a single chunk on an annual basis. Like how should we think about the income statement earnings impact in kind of the most granular way?

Chris Pietz, CEO, Miriam Pharmaceuticals: Yes, the dynamic that you’re talking about, some of these tender type orders, we do expect to see that from some of the distributors and partners where you could see kind of more sizable orders that cover six to twelve months of supply for a given geography. So the international side of the business, as we’ve actually seen historically, you can have kind of bigger quarters because of some of those orders from distributors that really are about their budget cycle when they have access to funds and when they’re securing supply for their market.

Unidentified speaker, Host: So talking a little bit about market evolution, you do have a competitor out in the field, with a similar mechanism of action, although different data set, different label, different price. Talk to me about how the competitive dynamics in Alagille versus PFIC, And to what extent is pricing a driver? To what extent is first mover advantage a driver? Like what are the key competitive metrics to follow in these markets right now?

Chris Pietz, CEO, Miriam Pharmaceuticals: Yes. On so speaking primarily about The U. S, where we’ve both products have had both indications now for some time. It’s a different situation in Europe. But in The U.

S, for Alagille syndrome, we think we’re probably ninety percent share of IBATS for Alagille syndrome. And a lot of that’s driven by first mover, right? We were there getting some of those patients seeking treatment, getting them started on LIV Marley. But what helps us hold that position also is the pricing dynamic where for Aligyl Syndrome, there is a pricing advantage for Liv Marley that we’ve seen show up and get recognized in some of the policies where Liv Marley is written as a first treatment for Aligill syndrome. So that is kind of a helpful dynamic to really hold our position in Aligill syndrome.

And PFIC is from a current prevalent share. Definitely, it’s clear that LIV Marley has a smaller piece of that. But what we’re seeing for new patient starts, I think we’re actually doing quite well. That pricing difference is not as straightforward because there’s a range of doses that are prescribed there. And so we have been able to pick up IBAT treatment naive PFIC patients.

And that’s one of the things that’s been really great about the PFIC launch. We saw a lot of this show up in the second half of last year from some of those kind of de novo, IBAT naive PFIC patients coming to live Marley first.

Unidentified speaker, Host: So as we think about some markets that are a little tougher to model, I think there’s been a lot of crosswinds in The EU in particular. Obviously, you’ve got a lot of individual small markets, you’ve got repricing in Germany, etcetera, that happens across the lifecycle of the drug. How should we think about modeling European growth given it’s a little more of a heterogeneous market? And it’s kind of the puts and takes, headwinds, tailwinds as people start to model growth in that market.

Chris Pietz, CEO, Miriam Pharmaceuticals: So from kind of thinking about the trends and how you model it, the Western Europe contribution to our international number that we point to, That is pretty steady and actually performs similar to The U. S, right, where you have a dispense is really closely tied to the actual revenue and the sale. And the distributors that are on top of that, that creates some of the kind of quarter to quarter lumpiness when you get a larger order. But underneath that for Europe, we think we’re in a we’re through some of those launch kind of price setting dynamics and for Western Europe expect that to be a kind of steadier growth curve similar to what you have in The U. S.

Unidentified speaker, Host: And we think about the dynamic of weight based dosing, you obviously have patients across a range of ages, so it’s a little hard to just magically slap a number on there, and a little irresponsible to do so. How should we think about the magnitude of that benefit? Is that something that we should see expect to play out over the next few years? Or is it something that the population will need to age into and more of a back half of the decade situation?

Chris Pietz, CEO, Miriam Pharmaceuticals: We expect it will be just a continued kind of tailwind and driver to growth over the life cycle of LIVMARY. When looking at one way to look at it is just the average dispense volume overall. That has kind of two components to it, right? You have the patients that have been on therapy for some time. But keep in mind, you’re starting many new patients, most of them younger, right?

A lot of the new starts are infants, newly presenting patients. So the average dispense overall because of that dynamic rises kind of gradually over time because you’re continuing to start younger patients that are at a lower dose as well as those that are prevalent on drug continuing to increase in weight over time. So that’s kind of just to bring it back to that. The average dispense has increased gradually over time, but it’s not the same as following like a single cohort of patients, which any given patient would have a bigger increase individually.

Unidentified speaker, Host: That makes sense. Let’s hop over to the adult side of the ledger. We had a fairly rich data year last year on PBC, PSC, getting a little more clarity on that opportunity. Give us a sense of how you think about competitive dynamics in PBC. I know this is a question I’ve asked you about 35 times.

But we know a little more about what that market is going to look like now than we did previously. And then we’ll hop to PSC next.

Chris Pietz, CEO, Miriam Pharmaceuticals: Yes. The you’re really challenging me to start with PBC. Like, PSC is that’s the real kind of from a competitive standpoint, the real exciting indication given the unique role that we’re trying

Unidentified speaker, Host: to save is it for us.

Chris Pietz, CEO, Miriam Pharmaceuticals: I’ll humor you. I’ll start with PBC. So within PBC, it’s important to break down kind of the standard of care and where the lines of treatment currently are. So PBC patients are almost universally treated with UDCA as a first line therapy, and that can help control liver labs, in particular, the alkaline phosphatase levels, what’s monitored for potentially progressive disease with UDCA treatment that might call for a second line therapy. Currently, that’s the PPARs or OCA.

So seladelpar, elafabranor, that’s where those were recently getting their got their approvals is in patients with elevated alkaline phosphatase despite UDCA treatment. And so there’s in the PBC segmentation about two thirds or sixty percent of patients are in that first line setting on UDCA. They haven’t yet progressed to be considered for a second line treatment. What’s unique about the valyxibat program and GSK also has an IVAT that’s taking a similar attack is that we’re we’ve enrolled patients across all settings. So similar to the just background prevalence of PBC patients, About two thirds of the patients in our study have been first line UDCA patients and about one third have been kind of the second line elevated alkaline phosphatase presentation.

So we expect our labeling to be across all lines of therapy for the traditional way to think about PBC treatment, and addressing the itch and symptomatic burden across all of these settings. ZUDCA does not actually have a great response for symptomatic improvement.

Unidentified speaker, Host: So now we get to the more important part of the conversation, well, the less complex one, I guess, actually, fairly straightforward. Let’s talk about PSC And you think about the opportunity set and sort of timing to launch commercialization, how we should think about market building there.

Chris Pietz, CEO, Miriam Pharmaceuticals: So the PSC indication for VELIXOVAT is really unique in that we given the mechanism and the dramatic response that you can drive on itch with an iDAT inhibitor, we can use that as an outcome in our program. So the PSC program, which is tracking well after the interim analysis last year, on track to complete enrollment in the second half of this year, six month endpoints, so it sets us up for the top line readout next year and really excited about getting to that data because it actually is a tractable endpoint that you can drive an outcome for the patient and measure that within a six month period and use that as a basis for an NDA submission.

Unidentified speaker, Host: So let’s talk a little bit about how to think about the opportunity set in terms of pricing strategy, etcetera. Is it reasonable to assume that you’re likely price will expand to value for PSC given that’s the more greenfield opportunity? Is that the reasonable assumption?

Chris Pietz, CEO, Miriam Pharmaceuticals: Absolutely. And in particular, because it comes first, right? So the pricing strategy, we approach it based on the first approval. Fully expect that to be PSC. We kind of you point to the PPAR launches as kind of the most recent approvals and prices set in the space.

But with PSC indication really unique in that we’re tracking to be the potentially the first and only product for this indication.

Unidentified speaker, Host: I’m going to pivot into the earlier stage pipeline. Talk to us a little bit about the strategy in Fragile X and more broadly, how that reflects your view on business development and the right type of asset to join the bag for you guys?

Chris Pietz, CEO, Miriam Pharmaceuticals: Yes. So on the I’ll give a little background on how we thought about looking for that program. It was really it was part of a deliberate search in genetic neurology on the back of bringing on the bile acid programs. So we were looking ahead to the Citexley approval and launch, having a dedicated sales team on the, really, the neurologists that are in these movement disorder clinics or tertiary centers that are treating some of these more complex neurological conditions and thought how can we leverage what we’re building for Citexiline. And that’s kind of how we that’s why we started looking in this space.

And as we’re looking across a number of different genetic neurological conditions, it’s actually a data set for a different PD4D inhibitor, DECautRI. So really clear, convincing Phase II data out of a program with Shionogi that was recently published that show that with a PD4D inhibitor, you can actually move cognitive functioning endpoints in fragile X patients. Real huge advance for programs for fragile X, and this just has not been seen with other programs. A lot of the prior research has been done on behavioral endpoints and not really getting out the cognitive potential. So when we saw that data set, we thought, well, these when you look at their data, it looks like they were limited in their dose window by some of the Emesis that’s on target mechanistic function on target mechanism for PD4 inhibitors in general.

And so we found three thousand three hundred and seventy nine, which actually has a quite wide therapeutic index for what we expect to be the target dose for Fragile X, mostly driven by just improved CNS penetration. So can get more drug to where it’s supposed to be, and we think we’ll be able to avoid some of the dose limiting emesis that’s mechanistic for PD4 inhibitors.

Unidentified speaker, Host: So before we dive into that, how do you think about your capacity to develop additional assets? Because this is you now rolled through the acquisition of TTX assets that Texas approved has moved entirely to commercial story. You’ve got Fragile X is brought on, still in the development stage of Phase two, etcetera, regulatory conversations. There’s still there’s still a bit of work to do into the development before that becomes a commercial story, market building, etcetera. How do you think about capacity or appetite to continue to expand the bag?

Or is that something that you think comes after the Fragile X story has moved a little bit further down the field?

Chris Pietz, CEO, Miriam Pharmaceuticals: We’re actively looking and interested in continuing to expand the Merum in general, right? We’ve been able to pull together a team that can execute in rare disease commercially, regulatory expertise and clinically and bringing more products to this team, I think we can add a lot of value. In terms of capacity, I mean, we think of it as we’ve now set up the company to be financially independent, cash flow generating with a strong commercial growth trajectory. So we have capacity and we’ll continue to be able to even grow that with margin expansion on the commercial side as long as we don’t disrupt that financial independence that we have currently. So that’s the way we think of it is there’s capacity that we could bring on clinical stage programs and that will continue to expand as we grow the commercial top line.

Unidentified speaker, Host: So maybe more of a CFO question, but talk to us a little bit about we talked about going cash flow positive this year. You obviously have some noncash amortization that lives in your gross margin post the CTX acquisition, which optically influences how things look like on our earnings but isn’t a cash expense. That dollar is already out the door. Talk to us how we should think about the amount of operating leverage in the business as structured now, recognizing there’s going to be a little bit of extra spend as you build out genetic neurology and it grows. What helps?

Chris Pietz, CEO, Miriam Pharmaceuticals: Yes. So the way we kind of analyze the kind of financial performance and the commercial margin in the business is that when you look at the basically cash commercial margin coming off of the current programs, it’s about 50%. So it was last year and expect that to expand that margin to expand into this year. So that commercial business contribution and margin expansion is something that we are see growing and will continue to drive for on the financial performance side. That then, what’s below that is what we’re reinvesting in the clinical side and is where you have potential for new product acquisition from that kind of 50% plus contribution margin.

Unidentified speaker, Host: And we think about one of the other conversations that I’ve had in terms of the ability of the company to not just accelerate growth and bend the growth curve upwards is to what extent the company is able to expand into different areas. Obviously, generative technology is novel, although you sort of daisy change your way into it through a transaction that was quite tangential to existing sales force. How do you think about what the sort of circle of competence for the company is? Do that continue to grow? At some point, do you say or is there a focus on it’s not a same rare disease, liver, neurology, we have room for one or more, but at some point, you get too diversified?

Chris Pietz, CEO, Miriam Pharmaceuticals: We talk about rare disease as the therapeutic area for Mirum. And what we kind of what we’ve seen in our experience and expanding into the for the Citexley commercial team and the ability to bring on a program like 03/1979. What matters is in these rare disease settings is kind of how expansive your field team needs to be. We’re able to leverage what we have on the kind of internal operations side, the payer team, the all the support functions. Those are highly leveraged as you add on another call point in these tertiary centers.

It’s quite efficient. So we don’t see ourselves limited into liver GI and just genetic neurology. There are other settings where the added field team would be 10 to 15 quite small increment if we did bring on another specialty area. And the rest of the team that we’ve built is highly leverageable, some really great leaders in rare disease and people that are excited to take on more programs. And

Unidentified speaker, Host: I guess changing the angle of consideration from therapeutic area to modality, you’ve been fairly disciplined, or maybe it’s just been a function of the opportunity set and remaining in what is a fairly high margin, simple from a manufacturing perspective, modalities, no cells, no viruses, largely small molecule, relatively straight from manufacturing perspective, but certainly not necessarily from a commercial perspective. Has there been any change in how you think about the universe of modalities that are appropriate and sort of would you be would you consider moving up the complexity curve Or is that something that’s less interesting to you?

Chris Pietz, CEO, Miriam Pharmaceuticals: We’re open to it to an extent. And the lens that we put on it is, is there an established third party ecosystem to be able to manufacture, right? And so that’s why we do exclude gene therapy, cell therapy, things that require a lot more capital intensive investment to be able to manufacture. But antibodies, for example, there’s a very well established third party CDMO infrastructure that would make us comfortable if that’s the right medicine and we’re excited about the therapy itself. So that’s kind of the criteria we put on it is just that we don’t have to go out and invest in building out our own infrastructure on the manufacturing side.

Unidentified speaker, Host: That makes sense to me. I think the final debate that I have with some investors is around exclusivity duration, because I think there’s a little bit of complexity because people look at the acquired CTX assets. Abzatexty obviously has orphan drug exclusivity extended now post the approval. And they say, if they as you continue to accelerate these assets, presuming you do bend the growth curve, at some point do they become large enough to attract generalization interests? How practically possible is it for a generic to enter these markets in the out years?

Chris Pietz, CEO, Miriam Pharmaceuticals: For the speaking about the bile acid program specifically, they relative to other medicines that where you do see generic entry, they’re still quite small, frankly, compared to some of these others. And the patient numbers are, in general, not that attractive for a new entrant because you do have to support the patient finding and prior authorization, some of these things that are really part of the investment in building a rare disease platform. So I mean, it doesn’t mean it’s not possible, but any new entrant we expect would be also a premium priced product because that’s what you need to have to support the infrastructure for the small patient number in these indications.

Unidentified speaker, Host: That makes sense. I think we’re coming down to the end of time. Thank you. As usual, it’s been a great conversation and looking forward to seeing more from you throughout the year.

Chris Pietz, CEO, Miriam Pharmaceuticals: Yes. Thanks again for hosting. We’re excited about the year for Miriam and more to come.

Unidentified speaker, Host: Awesome. A pleasure as always.

Chris Pietz, CEO, Miriam Pharmaceuticals: Thanks, Mani.

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