Mirum Pharmaceuticals, Inc. Q2 FY2025 earnings call

Commercial Performance - Q2 had total net product sales of $128M, driven by Livmarli in US and international, and bile acid portfolio. - In US, Livmarli had strong demand in Alagille and PFIC, with more PFIC patients than anticipated due to increased disease awareness. - Internationally, Livmarli had durable growth with $31M in net product sales, including Takeda's launch in Japan. - Bile acid portfolio had $40M in revenue from CTEXLI and COBACHOLBAM. ### Pipeline - VISTAS Phase IIb study in PSC on track to complete enrollment this quarter, with top line data expected Q2 2026. - VANTAGE PBC and EXPAND studies showing momentum. - Phase II study of MRM-3379 in Fragile X syndrome initiated after FDA feedback. ### Financials - Total net product revenue $128M, 64% increase y-o-y. - Operating expense $133M, cash flow positive for quarter and expected full year, with cash, cash equivalents, and investments at $322M.

Total net product sales for Q2 were approximately $128 million. Livmarli contributed significantly with $57 million in net product sales in the US (driven by Alagille syndrome and PFIC) and $31 million internationally. The bile acid portfolio, including CTEXLI and COBACHOLBAM, contributed approximately $40 million. Livmarli's revenue contribution was substantial, with growth in both US and international markets, and the bile acid portfolio also showing solid performance.

- Raised full-year guidance to $490M-$510M, positioning for ~50% top line growth. ### - VISTAS Phase IIb study in PSC on track for enrollment completion this quarter and top line data Q2 2026. ### - Phase II study of MRM-3379 in Fragile X syndrome initiated post-FDA feedback.

- Risks and uncertainties inherent in forward-looking statements, including potential differences between actual results and discussed results due to unforeseen events. ### - Uncertainties related to clinical trial outcomes and market adoption of pipeline products.

Q: Congrats on another great quarter. First, I just wanted to ask on Livmarli. What are you seeing for overall therapy persistence rates? And has that changed at all over the last couple of years? And then on the pipeline, for the ongoing VISTAS PSC trial, is there anything you're seeing on a blinded basis that gives you increased confidence? Maybe it's blended pruritus variability tracking within expectations, baseline characteristics continuing to come in as expected? Or anything else you can give us there would be really helpful.

A: Thanks, Gavin, for the question. I'll let Peter speak to the persistence question and then let Joanne comment a little bit about how VISTAS conduct is going. Peter Radovich: Yes. Thanks for the question, Gavin. In terms of persistence, our information is most stable from the Alagille indication where we've got patients that have been on several years or some of them approaching a decade. And if you think about persistence, probably 70% to 75% are on after 1 year. So that's the kind of attrition in year 1. And then in subsequent years, the attrition is much less than that. So that's probably the way to think about it analogy. And then PFIC, it's just probably a bit too early to comment. Joanne M. J. Quan: Gavin, this is Joanne. Thanks for the question. With regards to your questions about VISTAS, we're feeling pretty confident. And part of it is that the standard deviation that we powered the study on was pretty conservative. So our best estimate is the standard deviation should come in less than that. So given that we powered the study, assuming a treatment difference of 1.75 with a standard deviation of 3, probably it's closer to 2. So I think that gives us added confidence. And I can also share with you that the baseline characteristics in general reflect the PSC population. So I think these are all points that give us some good confidence kind of proceeding forward as we're getting the last patients in the screening [ going forward ].

Q: Congrats on the quarter. Can you provide details on the expected revenue distribution between Livmarli and the Bile Acid business for the remainder of the year?

A: Thanks for the question. We're not breaking down guidance by specific products. But one thing I would say is that some of the trends that we've seen year-to-date, we expect those to kind of, in general, continue moving forward. So that's kind of the best color I can give on how it breaks down in that $490 million to $510 million range.

Q: Congrats on the quarter. I wanted to ask what main drivers are you attributing to the growth that we're seeing in Livmarli sales? And then also how meaningful of an impact on script volumes are you seeing specifically due to the availability of the tablet format in Livmarli?

A: Thanks, Ryan, for the question. I'll give a first comment and let Peter add on to it. I think one of the -- there are several dynamics going on here. I think one in general that we've noticed is really just as PFIC has been added in the U.S., building awareness of availability of genetic testing and the concept of later onset PFIC diagnoses, which -- to be honest, when we got the label expansion and we're initially starting out in PFIC, we thought was pretty minimal. What we're finding is that it is -- it's just -- it's more -- there are more of them out there than we originally expected. So that's one of the drivers that we've actually deployed against over the past 12 months. Peter Radovich: Yes. I think that is one of the main drivers, really growing the pie and PFIC, if you will, the total market for the class in that setting. Also happy with the continued growth in Alagille syndrome and certainly, the international business has performed well. In terms of your question about the tablet, that was introduced in the month of June. So obviously, part of our comments there at the outset that didn't have an effect this quarter, but certainly encouraged. We had a lot of positive feedback from patients and providers who have chosen to go to the tablet since then.

Q: Two on Livmarli. Can you discuss any inventory impacts in the second quarter? And also, could you provide a little more insight on the Takeda order cadence? Do you expect it to be more of a seasonal trend? Or would it be more regular than that?

A: Yes. Thanks for the question, Luke. As far as inventory, it's really only relevant in so far as Japan and Takeda goes. No inventory in the business in the U.S. or Europe anywhere else. With Takeda, it is kind of large periodic orders that happened from time -- from -- we expect there'll probably be another one this year, but we don't have perfect line of sight into it. There's variable consideration placed on it when the order comes. So that's why in subsequent quarters, the estimate can change, but that's kind of the best color we give to you. We'd expect quarter-to-quarter variability there.

Q: Congratulations on the quarter as well. Maybe just a question on Fragile X. It sounds like you made some nice progress interacting with the FDA on the trial design. Just curious if there's anything else you need feedback on or from the FDA or any next steps before you start that study in the fourth quarter?

A: Yes. Thanks for the question. So we're actually good to go. We have the clearance from the IND, so we have a Study May Proceed letter. We've engaged a lot with the patient community and also the physician community to make sure they -- we've incorporated their comments into the design of the study. So we feel pretty good in terms of where we are and certainly on track to enroll the first patient by the end of the year.

Q: Congrats on the quarter. Just curious how well penetrated do you guys think you are in the Alagille and PFIC markets, kind of looking at your commentary that Livmarli can be a $1 billion product. Wondering how you see that broken out by Alagille and PFIC. And then just one on the pipeline. I know Fragile X design is pretty ironed out, but are there any specific elements you're particularly interested in from Shionogi's update later this year?

A: Yes. Thanks for the question. I can touch on the last point first and then pass it over to Peter to talk about some of the sizing for the various components for Livmarli. In terms of the Phase II precedent data from the Shionogi program and the upcoming Phase III a couple of thoughts that we have on it. First, the Phase II is great proof of concept out there and kind of what got us excited about 3379 and the ability to have a potentially wider therapeutic index, get more of the drug into the CNS. And in terms of kind of what we are looking for out of the Phase III, that differentiated profile that we have, I think, kind of makes us really interested to run our proof of concept kind of regardless of the outcome. Expect we're not going to learn a lot from any top line release, but we'll kind of be looking closely and see if there's anything to incorporate into the future studies in the program. Peter Radovich: And in terms of your question, Ryan, about penetration and opportunity. If you think about the U.S. in Alagille syndrome, we think we're approaching 50% penetration, but still every quarter, including Q2, adding patients in both infants as well as kind of older patients who are more prevalent in that prevalent addressable pool. So still see the potential to keep growing Alagille further and further in subsequent quarters as we have and grow that business. PFIC has been really interesting, as Chris mentioned in his comments, we're growing the pie right now as we speak. I think traditionally, the field and others in the area thought about PFIC is really an infant onset disease. And if it's not that scenario, then it's not PFIC. And I think what we've shown through our education and genetic testing efforts is that there's a lot more there than was previously thought. So we have kind of less visibility than kind of how big that could be. I think historically, we thought about PFIC as being about 1/3 of Alagille. Quite frankly, that's probably an underestimate at this point. So excited to define that as we move forward. Christopher Peetz: And I'd add on the one other component of when you think about the total Livmarli potential, the $1 billion-plus number that we're looking at, the EXPAND study also is a big contributor there, where the EXPAND patient population is really at least the size of PFIC and that kind of the conservative view of it. And all of these dynamics kind of continuing to build over time, the patients on therapy and ultimately, the size of the brand.

Q: One for me on the EXPAND study. I was wondering if you could share if any of those eligible patients are already on Livmarli through compassionate use or other exceptions?

A: Yes. Thanks for the question. I'll let Joanne speak a little bit to the background of how we thought came upon designing the EXPAND study kind of speaks to that question. Joanne M. J. Quan: Yes. Thanks for the question. So really, the EXPAND study came around because we had a lot of requests for [ compassionate ] use in these patients with cholestatic pruritus from these other settings. And so we're taking patients who have not previously been treated in order to assess the treatment response in this setting. So, so far, we're encouraged by the engagement we've heard from sites and also just the interest from patient populations as well.

Q: I know a few years ago, $500 million was viewed as kind of the peak for Livmarli. This is obviously a dramatic shift. How much of it comes from potential from the new indications versus PFIC and ALGS, new potential indications?

A: Yes. Thanks for the question. The $500 million, I think you're referencing is we used to kind of give a size for the indication of Alagille in the U.S., just kind of the market sizing. So this is kind of the first time with these indications that we've put out guidance on where we think Livmarli can ultimately get to. So a slightly different lens than kind of indication sizing. And really, a lot of the confidence in doing that is just how much we're seeing come together across all these different settings. So the 3 indications, Alagille, PFIC and EXPAND in the U.S. quite sizable. What we're seeing on the international side, also kind of running ahead of where our expectations were. So a lot of this is kind of a change in what we've seen so far this year in terms of uptake and things that we're doing directly as well as distributors and partners and the success that they're seeing.

Q: Two for me. One on PSC. You guys estimate that there's about 65% of the population with active pruritus. I'm wondering if there's any evidence that that's due specifically due to excess bile acids or if there could be any other drivers of pruritus in that group? And then second one, just wondering on CTX, if you guys have seen any inflection now that you can promote and what you expect for that long term?

A: Yes. Thanks for the question. I'll pass this over to Peter and Joanne to speak to the 2 components, and let Peter lead off with CTX. Peter Radovich: Yes. We're certainly excited about the FDA approval now, first full quarter since that here. A lot of our efforts are on patient finding across different specialties where patients present. Not expecting -- I think it's a gradual steady build in CTX. Patient finding is laborious, but excited about the potential there to grow [ this ] longer term. Joanne? Joanne M. J. Quan: Yes. Yes, thanks for the question. Regards to PSC, we do think that bile acids do have a role here. However, the pathophysiology is a bit different than some of the other diseases like Alagille and PFIC that we studied in the past. In reality, what we're treating is cholestasis. And therefore, there's an intrahepatic component to it that we don't measure. What we think is that what we're measuring in serum bile acids is really kind of spillover. And so we think that the serum bile acid level is probably less important when we're thinking about a disease like PSC, probably more important when you're thinking of Alagille and PFIC for instance. So I think slightly different disease pathophysiology, but still kind of the important central feature here is cholestasis.

Q: I have 2 of them. The first one being on Livmarli. So you made some remarks regarding how Takeda is managing the Japanese part of the collaboration. Any remarks on how you're going about in Europe? And also within Europe, what sort of efforts are you making to increase your penetration? So that's question number one. And the question number two is on the -- based on the EXPAND study, what sort of additional population -- patient population can you bring to Livmarli?

A: Great. Thanks for the question. And I can make a couple of comments on kind of end market Livmarli and then have Peter speak to the opportunity [ and ] expand. And so commentary on Europe and kind of where we're at, what I'd say is the European performance to date is largely Alagille syndrome. So kind of what's to come and most exciting in some of our direct European markets is now bringing forward the PFIC indication and adding that in. It's right now kind of coming through it's the reimbursement steps for adding that indication. So that's what's kind of on the horizon in Europe. And maybe speak to expand. Peter Radovich: Yes. And in terms of expanding, a lot of different ultra-rare patient populations individually when you look at the underlying kind of etiology cause of the cholestatic pruritus that could pull in. Certainly, biliary atresia patients with cholestatic pruritus will be a portion of that, but there are also several others. And we hear about these, as Joanne mentioned earlier, through compassionate access requests and from sites who have these patients in their clinics, and they don't have anything to offer them. So excited about the potential to study them and potentially have an option for them.